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Clinical Neurophysiology

Back Clinic Clinical Neurophysiology Support. El Paso, TX. Chiropractor, Dr. Alexander Jimenez discusses clinical neurophysiology. Dr. Jimenez will explore the clinical significance and functional activities of peripheral nerve fibers, the spinal cord, brainstem, and brain in the context of visceral and musculoskeletal disorders. Patients will gain an advanced understanding of the anatomy, genetics, biochemistry, and physiology of pain in relation to various clinical syndromes. Nutritional biochemistry related to nociception and pain will be incorporated. And the implementation of this information into therapy programs will be emphasized.

Our team takes great pride in bringing our families and injured patients only proven treatment protocols. By teaching complete holistic wellness as a lifestyle, we also change not only our patients’ lives but their families as well. We do this so that we may reach as many El Pasoans who need us, no matter the affordability issues. For answers to any questions you may have please call Dr. Jimenez at 915-850-0900.


Overview of the Pathophysiology of Neuropathic Pain

Overview of the Pathophysiology of Neuropathic Pain

Neuropathic pain is a complex, chronic pain condition that is generally accompanied by soft tissue injury. Neuropathic pain is common in clinical practice and also poses a challenge to patients and clinicians alike. With neuropathic pain, the nerve fibers themselves may be either damaged, dysfunctional or injured. Neuropathic pain is the result of damage from trauma or disease to the peripheral or central nervous system, where the lesion may occur at any site. As a result, these damaged nerve fibers can send incorrect signals to other pain centers. The effect of a nerve fiber injury consists of a change in neural function, both at the region of the injury and also around the injury. Clinical signs of neuropathic pain normally include sensory phenomena, such as spontaneous pain, paresthesias and hyperalgesia.

 

Neuropathic pain, as defined by the International Association of the Study of Pain or the IASP, is pain initiated or caused by a primary lesion or dysfunction of the nervous system. It could result from damage anywhere along the neuraxis: peripheral nervous system, spinal or supraspinal nervous system. Traits that distinguish neuropathic pain from other kinds of pain include pain and sensory signs lasting beyond the recovery period. It’s characterized in humans by spontaneous pain, allodynia, or the experience of non-noxious stimulation as painful, and causalgia, or persistent burning pain. Spontaneous pain includes sensations of “pins and needles”, burning, shooting, stabbing and paroxysmal pain, or electric-shock like pain, often associated with dysesthesias and paresthesias. These sensations not only alter the patient’s sensory apparatus, but also the patient’s well-being, mood, attention and thinking. Neuropathic pain is made up of both “negative” symptoms, such as sensory loss and tingling sensations, and “positive” symptoms, such as paresthesias, spontaneous pain and increased feeling of pain.

 

Conditions frequently related to neuropathic pain can be classified into two major groups: pain due to damage in the central nervous system and pain because of damage to the peripheral nervous system. Cortical and sub-cortical strokes, traumatic spinal cord injuries, syringo-myelia and syringobulbia, trigeminal and glossopharyngeal neuralgias, neoplastic and other space-occupying lesions are clinical conditions that belong to the former group. Nerve compression or entrapment neuropathies, ischemic neuropathy, peripheral polyneuropathies, plexopathies, nerve root compression, post-amputation stump and phantom limb pain, postherpetic neuralgia and cancer-related neuropathies are clinical conditions that belong to the latter group.

 

Pathophysiology of Neuropathic Pain

 

The pathophysiologic processes and concepts underlying neuropathic pain are multiple. Prior to covering these processes, a review of ordinary pain circuitry is critical. Regular pain circuitries involve activation of a nociceptor, also known as the pain receptor, in response to a painful stimulation. A wave of depolarization is delivered to the first-order neurons, together with sodium rushing in via sodium channels and potassium rushing out. Neurons end in the brain stem in the trigeminal nucleus or in the dorsal horn of the spinal cord. It is here where the sign opens voltage-gated calcium channels in the pre-synaptic terminal, allowing calcium to enter. Calcium allows glutamate, an excitatory neurotransmitter, to be released into the synaptic area. Glutamate binds to NMDA receptors on the second-order neurons, causing depolarization.

 

These neurons cross through the spinal cord and travel until the thalamus, where they synapse with third-order neurons. These then connect to the limbic system and cerebral cortex. There is also an inhibitory pathway that prevents pain signal transmission from the dorsal horn. Anti-nociceptive neurons originate in the brain stem and travel down the spinal cord where they synapse with short interneurons in the dorsal horn by releasing dopamine and norepinephrine. The interneurons modulate the synapse between the first-order neuron as well as the second-order neuron by releasing gamma amino butyric acid, or GABA, an inhibitory neurotransmitter. Consequently, pain cessation is the result of inhibition of synapses between first and second order neurons, while pain enhancement might be the result of suppression of inhibitory synaptic connections.

 

Pathophysiology of Neuropathic Pain Diagram | El Paso, TX Chiropractor

 

The mechanism underlying neuropathic pain, however, aren’t as clear. Several animal studies have revealed that lots of mechanisms may be involved. However, one has to remember that what applies to creatures may not always apply to people. First order neurons may increase their firing if they’re partially damaged and increase the amount of sodium channels. Ectopic discharges are a consequence of enhanced depolarization at certain sites in the fiber, resulting in spontaneous pain and movement-related pain. Inhibitory circuits might be diminished in the level of the dorsal horn or brain stem cells, as well as both, allowing pain impulses to travel unopposed.

 

In addition, there might be alterations in the central processing of pain when, because of chronic pain and the use of some drug and/or medications, second- and third-order neurons can create a “memory” of pain and become sensitized. There’s then heightened sensitivity of spinal neurons and reduced activation thresholds. Another theory demonstrates the concept of sympathetically-maintained neuropathic pain. This notion was demonstrated by analgesia following sympathectomy from animals and people. However, a mix of mechanics can be involved in many chronic neuropathic or mixed somatic and neuropathic pain conditions. Among those challenges in the pain field, and much more so as it pertains to neuropathic pain, is the capability to check it. There is a dual component to this: first, assessing quality, intensity and advancement; and second, correctly diagnosing neuropathic pain.

 

There are, however, some diagnostic tools that may assist clinicians in evaluating neuropathic pain. For starters, nerve conduction studies and sensory-evoked potentials may identify and quantify the extent of damage to sensory, but not nociceptive, pathways by monitoring neurophysiological responses to electrical stimuli. Additionally, quantitative sensory testing steps perception in reaction to external stimuli of varying intensities by applying stimulation to the skin. Mechanical sensitivity to tactile stimuli is measured with specialized tools, such as von Frey hairs, pinprick with interlocking needles, as well as vibration sensitivity together with vibrameters and thermal pain with thermodes.

 

It is also extremely important to perform a comprehensive neurological evaluation to identify motor, sensory and autonomic dysfunctions. Ultimately, there are numerous questionnaires used to distinguish neuropathic pain in nociceptive pain. Some of them include only interview queries (e.g., the Neuropathic Questionnaire and ID Pain), while others contain both interview questions and physical tests (e.g., the Leeds Assessment of Neuropathic Symptoms and Signs scale) and the exact novel tool, the Standardized Evaluation of Pain, which combines six interview questions and ten physiological evaluations.

 

Neuropathic Pain Diagram | El Paso, TX Chiropractor

 

Treatment Modalities for Neuropathic Pain

 

Pharmacological regimens aim at the mechanisms of neuropathic pain. However, both pharmacologic and non-pharmacologic treatments deliver complete or partial relief in just about half of patients. Many evidence-based testimonials suggest using mixtures of drugs and/or medications to function for as many mechanisms as possible. The majority of studies have researched mostly post-herpetic neuralgia and painful diabetic neuropathies but the results may not apply to all neuropathic pain conditions.

 

Antidepressants

 

Antidepressants increase synaptic serotonin and norepinephrine levels, thereby enhancing the effect of the descending analgesic system associated with neuropathic pain. They’ve been the mainstay of neuropathic pain therapy. Analgesic actions might be attributable to nor-adrenaline and dopamine reuptake blockade, which presumably enhance descending inhibition, NMDA-receptor antagonism and sodium-channel blockade. Tricyclic antidepressants, such as TCAs; e.g., amitriptyline, imipramine, nortriptyline and doxepine, are powerful against continuous aching or burning pain along with spontaneous pain.

 

Tricyclic antidepressants have been proven significantly more effective for neuropathic pain than the specific serotonin reuptake inhibitors, or SSRIs, such as fluoxetine, paroxetine, sertraline and citalopram. The reason may be that they inhibit reuptake of serotonin and nor-epinephrine, while SSRIs only inhibit serotonin reuptake. Tricyclic antidepressants can have unpleasant side effects, including nausea, confusion, cardiac conduction blocks, tachycardia and ventricular arrhythmias. They can also cause weight gain, a reduced seizure threshold and orthostatic hypotension. Tricyclics have to be used with care in the elderly, who are particularly vulnerable to their acute side effects. The drug concentration in the blood should be monitored to avoid toxicity in patients who are slow medication metabolizers.

 

Serotonin-norepinephrine reuptake inhibitors, or SNRIs, are a new class of antidepressants. Like TCAs, they seem to be more effective than SSRIs for treating neuropathic pain because they also inhibit reuptake of both nor-epinephrine and dopamine. Venlafaxine is as effective against debilitating polyneuropathies, such as painful diabetic neuropathy, as imipramine, in the mention of TCA, and the two are significantly greater than placebo. Like the TCAs, the SNRIs seem to confer benefits independent of their antidepressant effects. Side effects include sedation, confusion, hypertension and withdrawal syndrome.

 

Antiepileptic Drugs

 

Antiepileptic drugs can be utilized as first-line treatment especially for certain types of neuropathic pain. They act by modulating voltage-gated calcium and sodium channels, by improving the inhibitory effects of GABA and by inhibiting excitatory glutaminergic transmission. Anti-epileptic medications have not been demonstrated to be effective for acute pain. In chronic pain cases, antiepileptic drugs seem to be effective only in trigeminal neuralgia. Carbamazepine is routinely employed for this condition. Gabapentin, which functions by inhibiting calcium channel function through agonist actions at the alpha-2 delta subunit of the calcium channel, is also known to be effective for neuropathic pain. However, gabapentin acts centrally and it might cause fatigue, confusion and somnolence.

 

Non-Opioid Analgesics

 

There is a lack of strong data supporting using non-steroidal anti inflammatory medications, or NSAIDs, in the relief of neuropathic pain. This may be due to the lack of an inflammatory component in relieving pain. But they have been utilized interchangeably with opioids as adjuvants in treating cancer pain. There have been reported complications, though, especially in severely debilitated patients.

 

Opioid Analgesics

 

Opioid analgesics are a subject of much debate in relieving neuropathic pain. They act by inhibiting central ascending pain impulses. Traditionally, neuropathic pain has been previously observed to be opioid-resistant, in which opioids are more suitable methods for coronary and somatic nociceptive types of pain. Many doctors prevent using opioids to treat neuropathic pain, in large part because of concerns about drug abuse, addiction and regulatory issues. But, there are many trials that have found opioid analgesics to succeed. Oxycodone was superior to placebo for relieving pain, allodynia, improving sleep and handicap. Controlled-release opioids, according to a scheduled basis, are recommended for patients with constant pain to encourage constant levels of analgesia, prevent fluctuations in blood glucose and prevent adverse events associated with higher dosing. Most commonly, oral preparations are used because of their greater ease of use and cost-effectiveness. Trans-dermal, parenteral and rectal preparations are generally used in patients who cannot tolerate oral drugs.

 

Local Anesthetics

 

Nearby acting anesthetics are appealing because, thanks to their regional action, they have minimal side effects. They act by stabilizing sodium channels at the axons of peripheral first-order neurons. They work best if there is only partial nerve injury and excess sodium channels have collected. Topical lidocaine is the best-studied representative of the course for neuropathic pain. Specifically, the use of this 5 percent lidocaine patch for post-herpetic neuralgia has caused its approval by the FDA. The patch seems to work best when there is damaged, but maintained, peripheral nervous system nociceptor function from the involved dermatome demonstrating as allodynia. It needs to be set directly on the symptomatic area for 12 hours and eliminated for another 12 hours and may be used for years this way. Besides local skin reactions, it is often well tolerated by many patients with neuropathic pain.

 

Miscellaneous Drugs

 

Clonidine, an alpha-2-agonist, was shown to be effective in a subset of patients with diabetic peripheral neuropathy. Cannabinoids have been found to play a role in experimental pain modulation in animal models and evidence of the efficacy is accumulating. CB2-selective agonists suppress hyperalgesia and allodynia and normalize nociceptive thresholds without inducing analgesia.

 

Interventional Pain Management

 

Invasive treatments might be considered for patients who have intractable neuropathic pain. These treatments include epidural or perineural injections of local anesthetics or corticosteroids, implantation of epidural and intrathecal drug delivery methods and insertion of spinal cord stimulators. These approaches are reserved for patients with intractable chronic neuropathic pain who have failed conservative medical management and also have experienced thorough psychological evaluation. In a study by Kim et al, it was shown that a spinal cord stimulator was effective in treating neuropathic pain of nerve root origin.

 

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Dr. Alex Jimenez’s Insight

With neuropathic pain, chronic pain symptoms occur due to the nerve fibers themselves being damaged, dysfunctional or injured, generally accompanied by tissue damage or injury. As a result, these nerve fibers can begin to send incorrect pain signals to other areas of the body. The effects of neuropathic pain caused by nerve fiber injuries includes modifications in nerve function both at the site of injury and at areas around the injury. Understanding the pathophysiology of neuropathic pain has been a goal for many healthcare professionals, in order to effectively determine the best treatment approach to help manage and improve its symptoms. From the use of drugs and/or medications, to chiropractic care, exercise, physical activity and nutrition, a variety of treatment approaches may be used to help ease neuropathic pain for each individual’s needs.

 

Additional Interventions for Neuropathic Pain

 

Lots of patients with neuropathic pain pursue complementary and alternative treatment options to treat neuropathic pain. Other well-known regimens used to treat neuropathic pain include acupuncture, percutaneous electrical nerve stimulation, transcutaneous electrical nerve stimulation, cognitive behavioral treatment, graded motor imagery and supportive treatment, and exercise. Among these however, chiropractic care is a well-known alternative treatment approach commonly utilized to help treat neuropathic pain. Chiropractic care, along with physical therapy, exercise, nutrition and lifestyle modifications can ultimately offer relief for neuropathic pain symptoms.

 

Chiropractic Care

 

What is known is that a comprehensive management application is crucial to combat the effects of neuropathic pain. In this manner, chiropractic care is a holistic treatment program that could be effective in preventing health issues associated with nerve damage. Chiropractic care provides assistance to patients with many different conditions, including those with neuropathic pain. Sufferers of neuropathic pain often utilize non-steroidal-anti-inflammatory medications, or NSAIDs, such as ibuprofen, or heavy prescription painkillers to help ease neuropathic pain. These may provide a temporary fix but need constant use to manage the pain. This invariably contributes to harmful side effects and in extreme situations, prescription drug dependence.

 

Chiropractic care can help improve symptoms of neuropathic pain and enhance stability without these downsides. An approach such as chiropractic care offers an individualized program designed to pinpoint the root cause of the issue. Through the use of spinal adjustments and manual manipulations, a chiropractor can carefully correct any spinal misalignments, or subluxations, found along the length of the spine, which could lower the consequences of nerve wracking via the realigning of the backbone. Restoring spinal integrity is essential to keeping a high-functioning central nervous system.

 

A chiropractor can also be a long-term treatment towards enhancing your overall well-being. Besides spinal adjustments and manual manipulations, a chiropractor may offer nutritional advice, such as prescribing a diet rich in antioxidants, or they may design a physical therapy or exercise program to fight nerve pain flair-ups. A long-term condition demands a long-term remedy, and in this capacity, a healthcare professional who specializes in injuries and/or conditions affecting the musculoskeletal and nervous system, such as a doctor of chiropractic or chiropractor, may be invaluable as they work to gauge favorable change over time.

 

Physical therapy, exercise and movement representation techniques have been demonstrated to be beneficial for neuropathic pain treatment. Chiropractic care also offers other treatment modalities which may be helpful towards the management or improvement of neuropathic pain. Low level laser therapy, or LLLT, for instance, has gained tremendous prominence as a treatment for neuropathic pain. According to a variety of research studies, it was concluded that LLLT had positive effects on the control of analgesia for neuropathic pain, however, further research studies are required to define treatment protocols that summarize the effects of low level laser therapy in neuropathic pain treatments.

 

Chiropractic care also includes nutritional advice, which can help control symptoms associated with diabetic neuropathy. During a research study, a low fat plant-based diet was demonstrated to improve glycemic control in patients with type 2 diabetes. After about 20 weeks of the pilot study, the individuals involved reported changes in their body weight and electrochemical skin conductance in the foot was reported to have improved with the intervention. The research study suggested a potential value in the low-fat plant-based diet intervention for diabetic neuropathy. Moreover, clinical studies found that the oral application of magnesium L-threonate is capable of preventing as well as restoring memory deficits associated with neuropathic pain.

 

Chiropractic care can also offer additional treatment strategies to promote nerve regeneration. By way of instance, enhancing the regeneration of axons has been suggested to help improve functional recovery after peripheral nerve injury. Electrical stimulation, together with exercise or physical activities, was found to promote nerve regeneration after delayed nerve repair in humans and rats, according to recent research studies. Both electrical stimulation and exercise were ultimately determined to be promising experimental treatments for peripheral nerve injury which seem ready to be transferred to clinical use. Further research studies may be needed to fully determine the effects of these in patients with neuropathic pain.

 

Conclusion

 

Neuropathic pain is a multifaceted entity with no particular guidelines to take care of. It’s best managed using a multidisciplinary approach. Pain management requires ongoing evaluation, patient education, ensuring patient follow-up and reassurance. Neuropathic pain is a chronic condition that makes the option for the best treatment challenging. Individualizing treatment involves consideration of the impact of the pain on the individual’s well-being, depression and disabilities together with continuing education and evaluation. Neuropathic pain studies, both on the molecular level and in animal models, is relatively new but very promising. Many improvements are anticipated in the basic and clinical fields of neuropathic pain hence opening the doorways to improved or new treatment modalities for this disabling condition. The scope of our information is limited to chiropractic as well as to spinal injuries and conditions. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at�915-850-0900�.

 

Curated by Dr. Alex Jimenez

 

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Additional Topics: Back Pain

 

Back pain is one of the most prevalent causes for disability and missed days at work worldwide. As a matter of fact, back pain has been attributed as the second most common reason for doctor office visits, outnumbered only by upper-respiratory infections. Approximately 80 percent of the population will experience some type of back pain at least once throughout their life. The spine is a complex structure made up of bones, joints, ligaments and muscles, among other soft tissues. Because of this, injuries and/or aggravated conditions, such as herniated discs, can eventually lead to symptoms of back pain. Sports injuries or automobile accident injuries are often the most frequent cause of back pain, however, sometimes the simplest of movements can have painful results. Fortunately, alternative treatment options, such as chiropractic care, can help ease back pain through the use of spinal adjustments and manual manipulations, ultimately improving pain relief.

 

 

 

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EXTRA IMPORTANT TOPIC: Low Back Pain Management

 

MORE TOPICS: EXTRA EXTRA:�Chronic Pain & Treatments

 

Pain Anxiety Depression In El Paso, TX.

Pain Anxiety Depression In El Paso, TX.

Pain Anxiety Depression�Everyone has experienced pain, however, there are those with depression, anxiety, or both. Combine this with pain and it can become pretty intense and difficult to treat. People that are suffering from depression, anxiety or both tend to experience severe and long term pain more so than other people.

The way anxiety, depression, and pain overlap each other is seen in chronic and in some disabling pain syndromes, i.e. low back pain, headaches, nerve pain and fibromyalgia. Psychiatric disorders contribute to the pain intensity and also increase the risk of disability.

Depression:�A (major depressive disorder or clinical depression) is a common but serious mood disorder. It causes severe symptoms that affect how an individual feels, thinks, and how the handle daily activities, i.e. sleeping, eating and working. To be diagnosed with depression, the symptoms must be present for at least two weeks.

  • Persistent sad, anxious, or �empty� mood.
  • Feelings of hopelessness, pessimistic.
  • Irritability.
  • Feelings of guilt, worthlessness, or helplessness.
  • Loss of interest or pleasure in activities.
  • Decreased energy or fatigue.
  • Moving or talking slowly.
  • Feeling restless & having trouble sitting still.
  • Difficulty concentrating, remembering, or making decisions.
  • Difficulty sleeping, early-morning awakening & oversleeping.
  • Appetite & weight changes.
  • Thoughts of death or suicide & or suicide attempts.
  • Aches or pains, headaches, cramps, or digestive problems without a clear physical cause and/or that do not ease with treatment.

Not everyone who is depressed experiences every symptom. Some experience only a few symptoms while others may experience several. Several persistent symptoms in addition to low mood are�required�for a diagnosis of major depression. The severity and frequency of symptoms along with the duration will vary depending on the individual and their particular illness. Symptoms can also vary depending on the stage of the illness.

PAIN ANXIETY DEPRESSION

Objectives:

  • What is the relationship?
  • What is the neurophysiology behind it?
  • What are the central consequences?

pain anxiety depression el paso tx.

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pain anxiety depression el paso tx.

pain anxiety depression el paso tx.

pain anxiety depression el paso tx.

pain anxiety depression el paso tx.

pain anxiety depression el paso tx.

pain anxiety depression el paso tx.

pain anxiety depression el paso tx.

pain anxiety depression el paso tx.

pain anxiety depression el paso tx.

pain anxiety depression el paso tx.

pain anxiety depression el paso tx.

pain anxiety depression el paso tx.

pain anxiety depression el paso tx.

pain anxiety depression el paso tx.

pain anxiety depression el paso tx.

pain anxiety depression el paso tx.

pain anxiety depression el paso tx.

Brain Changes In Pain

pain anxiety depression el paso tx.

pain anxiety depression el paso tx.

pain anxiety depression el paso tx.

pain anxiety depression el paso tx.

pain anxiety depression el paso tx.

pain anxiety depression el paso tx.

pain anxiety depression el paso tx.

pain anxiety depression el paso tx.

pain anxiety depression el paso tx.

Figure 1 Brain pathways, regions and networks involved in acute and chronic pain

pain anxiety depression el paso tx.

Davis, K. D. et al. (2017) Brain imaging tests for chronic pain: medical, legal and ethical issues and recommendations Nat. Rev. Neurol. doi:10.1038/nrneurol.2017.122

pain anxiety depression el paso tx.

pain anxiety depression el paso tx.

PAIN, ANXIETY AND DEPRESSION

Conclusion:

  • Pain, especially chronic is associated with depression and anxiety
  • The physiological mechanisms leading to anxiety and depression can be multifactorial in nature
  • Pain causes changes in brain structure and function
  • This change in structure and function can alter the ability for the brain to modulate pain as well as control mood.

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What is Neuropathic Pain?

What is Neuropathic Pain?

When the sensory system is affected by injury or disease, the nerves within that system can’t work properly to transmit sensations and feelings into the brain. This frequently contributes to a feeling of numbness, or lack of sensation. However, in certain cases, when this system is damaged, people may experience pain in the affected area.

 

Neuropathic pain does not start abruptly or resolve quickly; it’s a chronic pain condition which leads to persistent pain symptoms. For most individuals, the intensity of their symptoms may wax and wane throughout the day. Although neuropathic pain is supposed to be related to peripheral nerve health issues, like neuropathy caused by diabetes or spinal stenosis, injuries to the brain or spinal cord may also lead to chronic neuropathic pain. Neuropathic pain is also referred to as nerve pain.

 

Neuropathic pain may be contrasted to nociceptive pain. Neuropathic pain does not develop to any specific circumstance or outside stimulus, but rather, the symptoms occur simply because the nervous system may not be working accordingly. As a matter of fact, individuals can also experience neuropathic pain even when the aching or injured body part is not actually there. This condition is called phantom limb pain, which may occur in people after they’ve had an amputation.

 

Nociceptive pain is generally acute and develops in response to a specific circumstance, such as when someone experiences a sudden injury, like hammering a finger with a hammer or stubbing a toe when walking barefoot. Moreover, nociceptive pain tends to go away once the affected site heals. The body contains specialized nerve cells, known as nociceptors, which detect noxious stimuli that could damage the body, such as extreme heat or cold, pressure, pinching, and exposure to chemicals. These warning signals are then passed along the nervous system to the brain, resulting in nociceptive pain.

 

Neuropathic Pain vs Nociceptive Pain Diagram | El Paso, TX Chiropractor

 

What are the Risk Factors for Neuropathic Pain?

 

Anything that contributes to a lack of function within the sensory nervous system can lead to neuropathic pain. As such, nerve health issues from carpal tunnel syndrome, or similar conditions, can ultimately trigger neuropathic pain. Trauma, resulting in nerve injury, may lead to neuropathic pain. Other conditions which could predispose individuals to developing neuropathic pain include: diabetes, vitamin deficiencies, cancer, HIV, stroke, multiple sclerosis, shingles, and even some cancer treatments.

 

What are the Causes of Neuropathic Pain?

 

There are many causes from which individuals may develop neuropathic pain. But on a cellular level, one explanation is an increased release of certain receptors that indicate pain, together with a diminished ability of the nerves to modulate these signals, leads to the sensation of pain originating from the affected region. Additionally, in the spinal cord, the region which exerts painful signs is rearranged with corresponding changes in hormones and loss of normally-functioning mobile bodies. Those alterations result in the perception of pain in the absence of external stimulation. In the brain, the ability to block pain can be affected following an injury, such as stroke or trauma from an injury. As time passes, additional cell damage happens and the feeling of pain continues. Neuropathic pain is also related to diabetes, chronic alcohol intake, certain cancers, vitamin B deficiency, diseases, other nerve-related diseases, toxins, and specific drugs.

 

What are the Symptoms of Neuropathic Pain?

 

Contrary to other neurological conditions, identification of neuropathic pain can be challenging. However, several, if any, objective signals may be present. Healthcare professionals have to decipher and translate an assortment of words which patients use to describe their pain. Patients may describe their symptoms as sharp, dull, hot, cold, sensitive, itchy, deep, stinging, burning, among a variety of other descriptive terms. Additionally, some patients may experience pain through light touch or pressure.

 

In an effort to help identify how much pain patients could be undergoing, different scales are often used. Patients are asked to rate their pain according to a visual scale or numerical graph. Many examples of pain scales exist, such as the one demonstrated below. Often, pictures of faces depicting a variety of levels of pain may be helpful when individuals have a difficult time describing the quantity of pain they are experiencing.

 

VAS Scale for Pain Diagram | El Paso, TX Chiropractor

 

Chronic Pain and Mental Health

 

For many, the impact of chronic pain may not be limited to the pain ; it may also negatively influence their mental state. New research studies conducted by scientists at the Northwestern University in Chicago can explain why individuals who have chronic pain also suffer with seemingly unrelated health issues, such as depression, stress, lack of sleep and difficulty concentrating.

 

The evaluation demonstrated that people with chronic pain show different regions of the brain which are always active, most specifically, the area associated with mood and attention. This continuous action rewires nerve connections from the brain and leaves chronic pain sufferers at greater risk for psychological problems. Researchers suggested that getting pain signals constantly could result in mental rewiring that adversely affects the mind. The rewiring compels their brains to devote mental resources differently to deal with everyday tasks, from mathematics, to recalling a shopping list, to feeling happy.

 

The pain-brain connection has been well recorded, at least anecdotally, and lots of healthcare professionals say they’ve seen first-hand the way the patient’s mental state can go downhill when they endure chronic pain. Misconceptions about the pain-brain connection may have emerged from a lack of evidence that pain has a measurable, lasting influence on the brain. Researchers expect that with additional research into the mechanisms of how chronic pain makes people more susceptible to mood disorders, people are going to have the ability to better manage their overall well-being.

 

Culture and Chronic Pain

 

Many things contribute to the way we experience and express pain, however, it has also been recently suggested by researchers that culture relates directly into the expression of pain. Our upbringing and societal values affect how we express pain and also its own nature, intensity and length. However, these variables aren’t as obvious as socio-psychological values, such as age and sex.

 

Research states that chronic pain is a multifaceted process and the concurrent interplay between pathophysiology, cognitive, affective, behavioral and sociocultural factors summate to what is referred to as the chronic pain experience. It’s emerged that chronic pain is experienced differently among patients of varied cultures and ethnicities.

 

Some cultures encourage the expression of pain, particularly in the southern Mediterranean and Middle East. Other individuals suppress it, as in the many lessons to our kids about behaving bravely and not crying. Pain is recognized as part of the human experience. We are apt to assume that communication about pain will seamlessly cross cultural boundaries. But people in pain are subject to the manners their civilizations have trained them to experience and express pain.

 

Both individuals in pain and healthcare professionals experience difficulties communicating pain across ethnic borders. In a matter like pain, where effective communication can have far-reaching implications for medical care, quality of life and potentially survival, the role of culture in pain communicating remains under-evaluated. Persistent pain is a multidimensional, a composite encounter formed by interweaving and co-influencing biological and psychosocial factors. Knowing the culmination of these factors is critical to understanding the differences of its manifestation and management.

 

How is Neuropathic Pain Diagnosed?

 

The diagnosis of neuropathic pain relies upon additional evaluation of an individual’s history. If underlying nerve damage is suspected, then analysis of the nerves together with testing may be justified. The most common means to assess whether or not a nerve is injured is using electrodiagnostic medicine. This medical subspecialty utilizes techniques of nerve conduction studies with electromyelography (NCS/EMG). Clinical evaluation may show evidence of loss of work, and can include evaluation of light touch, the capacity to differentiate sharp out of dull pain and the ability to discern temperature, as well as the evaluation of vibration.

 

After a thorough clinical examination is completed, the electrodiagnostic analysis could be planned. These studies are conducted by specially trained neurologist and physiatrists. If neuropathy is suspected, a hunt for reversible causes ought to be accomplished. This can include blood function for vitamin deficiencies or thyroid problems, and imaging studies to exclude a structural lesion affecting the spinal cord. Depending on the results of this testing, there might be a means to decrease the intensity of the neuropathy and possibly reduce the pain that a patient is undergoing.

 

Regrettably, in many conditions, even good control of the underlying cause of the neuropathy can’t reverse the neuropathic pain. This is commonly seen in patients with diabetic neuropathy. In rare instances, there may be signs of changes in the skin and hair growth pattern in an affected region. These alterations may be associated with changes in perspiration. If present, these changes can help identify the likely presence of neuropathic pain related to a condition known as complex regional pain syndrome.

 

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Dr. Alex Jimenez’s Insight

Neuropathic pain is a chronic pain condition which is generally associated with direct damage or injury to the nervous system or nerves. This type of pain is different from nociceptive pain, or the typical sensation of pain. Nociceptive pain is an acute or sudden sensation of pain which causes the nervous system to send signals of pain immediately after the trauma occurred. With neuropathic pain, however, patients may experience shooting, burning pain without any direct damage or injury. Understanding the possible causes of the patient’s neuropathic pain versus any other type of pain, can help healthcare professionals find better ways to treat chronic pain conditions.

 

What is the Treatment for Neuropathic Pain?

 

Various medicines are used in an attempt to treat neuropathic pain. The majority of these drugs are utilized off-label, which means that the medicine was approved by the FDA to treat different conditions and was then recognized as being advantageous to treat neuropathic pain. Tricyclic antidepressants, such as amitriptyline, nortriptyline and desipramine, have been prescribed for management of neuropathic pain for several years.

 

Some individuals find that these may be very effective in giving them relief. Other kinds of antidepressants have been shown to offer some relief. Selective serotonin reuptake inhibitors, or SSRIs, such as paroxetine and citalopram, and other antidepressants , such as venlafaxine and bupropion, have been utilized in certain patients. Another frequent treatment of neuropathic pain incorporates antiseizure medications, including carbamazepine, phenytoin, gabapentin, lamotrigine, and others.

 

In acute cases of painful neuropathy which don’t respond to first-line brokers, drugs typically utilized to treat heart arrhythmias may be of some benefit; however, these can lead to significant side effects and often have to be monitored closely. Medications applied directly to the skin can offer modest to perceptible benefit for some patients. The forms commonly used include lidocaine (in patch or gel type) or capsaicin.

 

Treating neuropathic pain is dependent on the underlying cause. If the cause is reversible, then the peripheral nerves can regenerate and the pain will abate; nonetheless, this reduction in pain may take several months to years. Several other alternative treatment options, including chiropractic care and physical therapy, may also be utilized in order to help relieve tension and stress along the nerves, ultimately helping to improve painful symptoms.

 

What is the Prognosis for Neuropathic Pain?

 

Many individuals with neuropathic pain are able to get some measure of aid, even when their pain persists. Although neuropathic pain isn’t dangerous to a patient, the presence of chronic pain can negatively affect quality of life. Patients with chronic nerve pain might suffer from sleep deprivation or mood disorders, including depression, anxiety and stress, as previously mentioned above. Because of the inherent alopecia and lack of sensory feedback, patients are at risk of developing injury or infection or unknowingly causing an escalation of a present injury. Therefore, it’s essential to seek immediate medical attention and follow specific guidelines directed by a healthcare professional for safety and caution.

 

Can Neuropathic Pain be Prevented?

 

The best way to prevent neuropathic pain is to avoid the development or progression of neuropathy. Monitoring and changing lifestyle options, including restricting the use of alcohol and tobacco; keeping a healthy weight to lower the chance of diabetes, degenerative joint disease, or stroke; and having great ergonomic form at work or when practicing hobbies to lower the risk of repetitive stress injury are strategies to decrease the probability of developing neuropathy and potential neuropathic pain. Make sure to seek immediate medical attention in the case of any symptoms associated with neuropathic pain in order to proceed with the most appropriate treatment approach.�The scope of our information is limited to chiropractic as well as to spinal injuries and conditions. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at�915-850-0900�.

 

Curated by Dr. Alex Jimenez

 

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Additional Topics: Back Pain

 

Back pain is one of the most prevalent causes for disability and missed days at work worldwide. As a matter of fact, back pain has been attributed as the second most common reason for doctor office visits, outnumbered only by upper-respiratory infections. Approximately 80 percent of the population will experience some type of back pain at least once throughout their life. The spine is a complex structure made up of bones, joints, ligaments and muscles, among other soft tissues. Because of this, injuries and/or aggravated conditions, such as herniated discs, can eventually lead to symptoms of back pain. Sports injuries or automobile accident injuries are often the most frequent cause of back pain, however, sometimes the simplest of movements can have painful results. Fortunately, alternative treatment options, such as chiropractic care, can help ease back pain through the use of spinal adjustments and manual manipulations, ultimately improving pain relief.

 

 

 

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EXTRA IMPORTANT TOPIC: Low Back Pain Management

 

MORE TOPICS: EXTRA EXTRA:�Chronic Pain & Treatments

 

Neuropathic Pain And Neurogenic Inflammation | El Paso, TX.

Neuropathic Pain And Neurogenic Inflammation | El Paso, TX.

If the sensory system becomes impacted by injury or disease, the nerves in that system can’t function in the transmitting of sensation to the brain. This can lead to a sensation of numbness, or lack of sensation. In some cases when the sensory system is injured, individuals can experience pain in the affected region. Neuropathic pain does not start quickly or ends quickly. It’s a chronic condition that leads to�symptoms of persistent pain. For many, the intensity of the symptoms can come and go throughout a day. Neuropathic pain is thought to be associated with peripheral nerve problems, i.e. neuropathy caused by diabetes, spinal stenosis, injury to the brain or spinal cord can also lead to chronic neuropathic pain.

NEUROPATHIC PAIN

Objectives:

  • What is it?
  • What is the pathophysiology behind it?
  • What are the causes
  • What are some of the pathways
  • How can we fix it?

NEUROPATHIC PAIN

  • Pain initiated or caused by a primary lesion or dysfunction in the somatosensory nervous system.
  • Neuropathic pain is usually chronic, difficult to treat and often resistant to standard analgesic management.

neuropathic pain el paso tx.

neuropathic pain el paso tx.

neuropathic pain el paso tx.

neuropathic pain el paso tx.PATHOGENESIS OF NEUROPATHIC PAIN

  • PERIPHERAL MECHANISMS
  • After a peripheral nerve lesion, neurons become more sensitive and develop abnormal excitability and elevated sensitivity to stimulation
  • This is known as…Peripheral Sensitization!

neuropathic pain el paso tx.

  • CENTRAL MECHANISMS
  • As a consequence of ongoing spontaneous activity arising in the periphery, neurons develop an increased background activity, enlarged receptive fields and increased responses to afferent impulses, including normal tactile stimuli
  • This is known as…Central Sensitization!

neuropathic pain el paso tx.

neuropathic pain el paso tx.COMMON CAUSES

Lesions or diseases of the somatosensory nervous system can lead to altered and disordered transmission of sensory signals into the spinal cord and the brain; common conditions associated with neuropathic pain include:

  • Postherpetic neuralgia
  • Trigeminal neuralgia
  • Painful radiculopathy
  • Diabetic neuropathy
  • HIV infection
  • Leprosy
  • Amputation
  • Peripheral nerve injury pain
  • Stroke (in the form of central post-stroke pain)

neuropathic pain el paso tx.

neuropathic pain el paso tx.

neuropathic pain el paso tx.

neuropathic pain el paso tx.

neuropathic pain el paso tx.

neuropathic pain el paso tx.

neuropathic pain el paso tx.

neuropathic pain el paso tx.

neuropathic pain el paso tx.

neuropathic pain el paso tx.

neuropathic pain el paso tx.

neuropathic pain el paso tx.

neuropathic pain el paso tx.PHANTOM LIMB PAIN & AUGMENTED REALITY

neuropathic pain el paso tx.

  • Phantom Limb Pain and AR

NEUROGENIC INFLAMMATION

Objectives:

  • What is it?
  • What is the pathophysiology behind it?
  • What are the causes
  • How can we fix it?

NEUROGENIC INFLAMMATION

  • Neurogenic inflammation is a neurally elicited, local inflammatory response characterized by vasodilation, increased vascular permeability, mast cell degranulation, and the release of neuropeptides including SP and calcitonin gene-related peptide (CGRP)
  • It appears to play an important role in the pathogenesis of numerous disease including migraine, psoriasis, asthma, fibromyalgia, eczema, rosacea, dystonia and multiple chemical sensitivity

neuropathic pain el paso tx.COMMON CAUSES

  • There are multiple pathways by which neurogenic inflammation may be initiated. It is well documented, using both animal models and isolated neurons in vitro, that capsaicin, heat, protons, bradykinin, and tryptase are upstream regulators of the intracellular calcium influx, which results in inflammatory neuropeptide release. In contrast, it is thought that prostaglandins E2 and I2, cytokines, interleukin-1, interleukin-6, and tumor necrosis factor do not cause neurotransmitter release themselves, but rather excite sensory neurons and thus lower the threshold for firing and cause augmented release of neuropeptides.
  • While neurogenic inflammation has been extensively studied and well documented in peripheral tissues, until recently the concept of neurogenic inflammation within the CNS has remained largely unexplored. Given the capacity for neurogenic inflammation to influence vascular permeability and lead to the genesis of edema, it has now been widely investigated for its potential to influence BBB permeability and vasogenic edema within the brain and spinal cord under varying pathological conditions.

neuropathic pain el paso tx.

neuropathic pain el paso tx.

Anatomy Of The Brain

Structural and Functional Mechanisms of Mechanoreceptors

Structural and Functional Mechanisms of Mechanoreceptors

We were all taught as children that there are 5 senses: sight, taste, sound, smell, and touch. The initial four senses utilize clear, distinct organs, such as the eyes, taste buds, ears, and nose, but just how does the body sense touch exactly? Touch is experienced over the entire body, both inside and outside. There is not one distinct organ that is responsible for sensing touch. Rather, there are tiny receptors, or nerve endings, around the entire body which sense touch where it occurs and sends signals to the brain with information regarding the type of touch that occurred. As a taste bud on the tongue detects flavor, mechanoreceptors are glands within the skin and on other organs that detect sensations of touch. They’re known as mechanoreceptors because they’re designed to detect mechanical sensations or differences in pressure.

 

Role of Mechanoreceptors

 

A person understands that they have experienced a sensation once the organ responsible for discovering that specific sense sends a message to the brain, which is the primary organ that processes and arranges all of the information. Messages are sent from all areas of the body to the brain through wires referred to as neurons. There are thousands of small neurons that branch out to all areas of the human body, and on the endings of many of these neurons are mechanoreceptors. To demonstrate what happens when you touch an object, we will use an example.

 

Envision a mosquito lands on your arm. The strain of this insect, so light, stimulates mechanoreceptors in that particular area of the arm. Those mechanoreceptors send a message along the neuron they are connected to. The neuron connects all the way to the brain, which receives the message that something is touching your body in the exact location of the specific mechanoreceptor that sent the message. The brain will act with this advice. Maybe it will tell the eyes to look at the region of the arm that detected the signature. And when the eyes tell the brain that there’s a mosquito on the arm, the brain may tell the hand to quickly flick it away. That’s how mechanoreceptors work. The purpose of the article below is to demonstrate as well as discuss in detail the functional organization and molecular determinants of mechanoreceptors.

 

Touch Sense: Functional Organization and Molecular Determinants of Mechanosensitive Receptors

 

Abstract

 

Cutaneous mechanoreceptors are localized in the various layers of the skin where they detect a wide range of mechanical stimuli, including light brush, stretch, vibration and noxious pressure. This variety of stimuli is matched by a diverse array of specialized mechanoreceptors that respond to cutaneous deformation in a specific way and relay these stimuli to higher brain structures. Studies across mechanoreceptors and genetically tractable sensory nerve endings are beginning to uncover touch sensation mechanisms. Work in this field has provided researchers with a more thorough understanding of the circuit organization underlying the perception of touch. Novel ion channels have emerged as candidates for transduction molecules and properties of mechanically gated currents improved our understanding of the mechanisms of adaptation to tactile stimuli. This review highlights the progress made in characterizing functional properties of mechanoreceptors in hairy and glabrous skin and ion channels that detect mechanical inputs and shape mechanoreceptor adaptation.

 

Keywords: mechanoreceptor, mechanosensitive channel, pain, skin, somatosensory system, touch

 

Introduction

 

Touch is the detection of mechanical stimulus impacting the skin, including innocuous and noxious mechanical stimuli. It is an essential sense for the survival and the development of mammals and human. Contact of solid objects and fluids with the skin gives necessary information to the central nervous system that allows exploration and recognition of the environment and initiates locomotion or planned hand movement. Touch is also very important for apprenticeship, social contacts and sexuality. Sense of touch is the least vulnerable sense, although it can be distorted (hyperesthesia, hypoesthesia) in many pathological conditions.1-3

 

Touch responses involve a very precise coding of mechanical information. Cutaneous mechanoreceptors are localized in the various layers of the skin where they detect a wide range of mechanical stimuli, including light brush, stretch, vibration, deflection of hair and noxious pressure. This variety of stimuli is matched by a diverse array of specialized mechanoreceptors that respond to cutaneous deformation in a specific way and relay these stimuli to higher brain structures. Somatosensory neurones of the skin fall into two groups: low-threshold mechanoreceptors (LTMRs) that react to benign pressure and high-threshold mechanoreceptors (HTMRs) that respond to harmful mechanical stimulation. LTMR and HTMR cell bodies reside within dorsal root ganglia (DRG) and cranial sensory ganglia (trigeminal ganglia). Nerve fibers associated with LTMRs and HTMRs are classified as A?-, A?- or C-fibers based on their action potential conduction velocities. C fibers are unmyelinated and have the slowest conduction velocities (~2 m/s), whereas A? and A? fibers are lightly and heavily myelinated, exhibiting intermediate (~12 m/s) and rapid (~20 m/s) conduction velocities, respectively. LTMRs are also classified as slowly, or rapidly adapting responses (SA- and RA-LTMRs) according to their rates of adaptation to sustained mechanical stimulus. They are further distinguished by the cutaneous end organs they innervate and their preferred stimuli.

 

Ability of mechanoreceptors to detect mechanical cues relies on the presence of mechanotransducer ion channels that rapidly transform mechanical forces into electrical signals and depolarise the receptive field. This local depolarisation, called receptor potential, can generate action potentials that propagate toward the central nervous system. However, properties of molecules that mediate mechanotransduction and adaptation to mechanical forces remain unclear.

 

In this review, we provide an overview of mammalian mechanoreceptor properties in innocuous and noxious touch in the hairy and glabrous skin. We also consider the recent knowledge about the properties of mechanically-gated currents in an attempt to explain the mechanism of mechanoreceptor�s adaptation. Finally, we review recent progress made in identifying ion channels and associated proteins responsible for the generation of mechano-gated currents.

 

Innocuous Touch

 

Hair Follicle-Associated LTMRs

 

The hair follicles represent hair shaft-producing mini-organs that detect light touch. Fibers associated with hair follicles respond to hair motion and its direction by firing trains of action potentials at the onset and removal of the stimulus. They are rapidly adapting receptors.

 

Cat and rabbit. In cat and rabbit coat, hair follicles can be divided in three hair follicle types, the Down hair, the Guard hair and the Tylotrichs. The Down hairs (underhair, wool, vellus)4 are the most numerous, the shortest and finest hairs of the coat. They are wavy, colorless and emerged in groups of two to four hairs from a common orifice in the skin. The Guard hairs (monotrichs, overhears, tophair)4 are slightly curved, either pigmented or unpigmented, and emerged singly from the mouths of their follicles. The tylotrichs are the least numerous, the longest and thickest hairs.5,6 They are pigmented or unpigmented, sometimes both and emerged singly from a follicle which is surrounded by a loop of capillary blood vessels. The sensory fibers supply to a hair follicle is located below the sebaceous gland and are attributed to A? or A?-LTMR fibers.7

 

In close apposition to the down hair shaft, just below the level of the sebaceous gland is the ring of lanceolate pilo-Ruffini endings. These sensory nerve endings are positioned in a spiral course around the hair shaft within the connective tissue forming the hair follicle. Within the hair follicle, there are also free nerve endings, some of them forming mechanoreceptors. Frequently, touch corpuscles (see glabrous skin) are surrounding the neck region of tylotrich follicle.

 

Properties of myelinated nerve endings in cat and rabbit hairy skin have been explored intensively in the 1930�1970 period (review in Hamann, 1995).8 Remarkably, Brown and Iggo, studying 772 units with myelinated afferent nerve fibers in the saphenous nerves from cat and rabbit, have classified responses in three receptor types corresponding to the movements of Down hairs (type D receptors), Guard hair (type G receptors) and Tylotrich hair (type T receptor).9 All the afferent nerve fiber responses have been brought together in the Rapidly Adapting receptor of type I (RA I) by opposition to the Pacinian receptor named RA II. RA I mechanoreceptors detect velocity of mechanical stimulus and have sharp border. They do not detect thermal variations. Burgess et al. also described a rapidly adapting field receptor that responds optimally to stroking of the skin or movement of several hairs, which was attributed to stimulation of pilo-Ruffini endings. None of the hair follicle response was attributed to C fiber activity.10

 

Mice. In the dorsal hairy skin of mice, three major types of hair follicles have been described: zigzag (around 72%), awl/auchene (around 23%) and guard or tylotrich (around 5%).11-14 Zigzag and Awl/auchenne hair follicles produce the thinner and shorter hair shafts and are associated with one sebaceous gland. Guard or tylotrich hairs are the longest of the hair follicle types. They are characterized by a large hair bulb associated with two sebaceous glands. Guard and awl/auchene hairs are arranged in an iterative, regularly spaced pattern whereas zigzag hairs densely populate skin areas surrounding the two larger hair follicle types [Fig. 1 (A1, A2 and A3)].

 

Figure 1 Organization and Projections of Cutaneous Mechanoreceptors | El Paso, TX Chiropractor

Figure 1. Organization and projections of cutaneous mechanoreceptors. In hairy skin, light brush and touch are mainly detected by the innervation around the hair follicles: awl/auchenne (A1), zigzag (A2) and guard (A3). Awl/auchene hairs are triply innervated by C-LTMR lanceolate endings (A4), A?-LTMR and A? rapidly adapting-LTMR (A6). Zigzag hair follicles are the shorter hair shafts and are innervated by both C-LTMR (A4) and A? -LTMR lanceolate endings (A5). The longest guard hair follicles are innervated by A? rapidly adapting-LTMR longitudinal lanceolate endings (A6) and are associated with A? slowly adapting-LTMR of touch dome endings (A7). The central projections of all these fibers terminate in distinct, but partially overlapping laminae of the spinal cord dorsal horn (C-LTMR in lamina II, A?-LTMR in lamina III and A?-LTMR in lamina IV and V). The projections of LTMR that innervate the same or adjacent hair follicles are aligned to form a narrow column in the spinal cord dorsal horn (B1 in gray). Only in hairy skin, a subpopulation of C-fibers free ending innervates the epidermis and responds to pleasant touch (A8). These C-touch fibers don�t respond to noxious touch and their pathway travel is not yet known (B2). In glabrous skin, innocuous touch is mediated by four types of LTMRs. The Merkel cell-neurite complex is in the basal layer of the epidermis (C1). This mechanoreceptor consists of an arrangement between many Merkel cells and an enlarged nerve terminal from a single A? fiber. Merkel cells exhibits finger like processes contacting keratinocytes (C2). The Ruffini ending is localized in the dermis. It is a thin cigar-shaped encapsulated sensory endings connected to A? fiber (C3). The Meissner corpuscle connected to A? nerve ending and is located in the dermal papillae. This encapsulated mechanoreceptor consists of packed down supportive cells arranged as horizontal lamellae surrounded by connective tissue (C4). Pacinian corpuscle is the deeper mechanoreceptor. One single A? unmyelinated nerve ending terminates in the center of this large ovoid corpuscle made of concentric lamellae. Projections of these A?-LTMR fibers in the spinal cord are divided in two branches. The principal central branch (B3) ascends in the spinal cord in the ipsilateral dorsal forming cuneate or gracile fascicles (B5) upon medulla level where the primary afferents make their first synapse (B6). The secondary neurons make a sensory decussation (B7) to form a tract on the medial lemniscus which ascends through the brainstem to the midbrain, specifically in the thalamus. Secondary branche of LTMR terminates in the dorsal horn in the lamina II, IV, V and interfere with the pain transmission (B4). Noxious touch is detected by the free nerve ending in the epidermis of both hairy (A9) and glabrous skin (C7). These mechanoreceptors are the ending of A?-HTMR and C-HTMR in close contact with neighboring keratinocytes (C6). A?-hTMR terminate in the lamina I and V; C-HTMR terminate in the lamina I and II (B8). At spinal cord dorsal horn level, primary afferents HTMRs make synapses with secondary neurons which cross the midline and climb to the higher brain structure in the anterolateral fascicle (B9, B10). LTMR, low threshold mechanoreceptor; HTMR, high threshold mechanoreceptor.

 

Recently, Ginty and collaborators used a combination of molecular-genetic labeling and somatotopic retrograde tracing approaches to visualize the organization of peripheral and central axonal endings of the LTMRs in mice.15 Their findings support a model in which individual features of a complex tactile stimulus are extracted by the three hair follicle types and conveyed via the activities of unique combinations of A?-, A?- and C- fibers to dorsal horn.

 

They showed that the genetic labeling of tyrosine hydroxylase positive (TH+) DRG neurones characterize a population of nonpeptidergic, small-diameter sensory neurones and allow for visualization of C-LTMR peripheral endings in the skin. Surprisingly, the axoneal branches of individual C-LTMRs were found to arborise and form longitudinal lanceolate endings that are intimately associated with zigzag (80% of endings) and awl/auchene (20% of endings), but not tylotrich hair follicles [Fig. 1 (A4)]. Longitudinal lanceolate endings have been long thought to belong exclusively to A?-LTMRs and therefore it was unexpected that the endings of C-LTMRs would form longitudinal lanceolate endings.15 These C-LTMRs have an intermediate adaptation in comparison with the slowly and rapidly adapting myelinated mechanoreceptors [Fig. 2 (C1)].

 

Figure 2 Tactile Receptors in Mammals | El Paso, TX Chiropractor

Figure 2. Tactile receptors in mammals: Cutaneous tactile receptors differentiate into innocuous touch supported by multiple receptors with low mechanical threshold (LTMRs) in glabrous and hairy skin and noxious touch supported by high mechanical threshold receptor (HTMRs). They make up nerve free endings that terminate mainly in epidermis. (A) Glabrous skin. A1: Meissner corpuscles detect skin motion and slipping of object in the hand. They are important for handing object and dexterity. Receptors rapidly adapt to stimulus, are connected to A? fibers and sparsely to C fibers and have large receptor field. A2: Ruffini corpuscles detect skin stretch and are important to detect finger position and handing object. Receptor slowly adapt to stimulus and maintained activity as long as the stimulus was applied. Receptors are connected to A? fibers and have large receptive field. A3: Pacinian corpuscles are deeper in the dermis and detect vibration. Receptors are connected to A? fibers; they rapidly adapt to stimulus and have the largest receptive field. (B) Whole skin. B1: Merkel-cell complexes are present in both glabrous skin and around hair. They are densely expressed in the hand and are important for texture perception and finest discrimination between two points. They are responsible for finger precision. Receptors are connected to A? fibers; they slowly adapt to stimulus and have short receptive field. B2: Noxious touch HTMRs with very slow adaptation to the stimulus, i.e., active as long as the nociceptive stimulus is applied. They are formed by the free nerve ending of A? and C-fibers associated to keratinocytes. (C) Hairy skin. C1: Hair follicles are associated with the different hair types. In mice Guard hairs are the longer and sparsely expressed one, awl/auchenne are of medium size and zigzag are the smallest and the most densely expressed hair. They are connected to A? fibers but also to A? and C-LTMRs fibers for awl/auchenne and zizag hair. They detect hair movement including pleasant touch during caress. They adapt rapidly or with intermediate kinetic to stimulus. C2: C-touch nerve endings correspond to a subtype of C fibers terminus with free ending characterized by a low mechanical threshold. They are supposed to encode for pleasant sensation induced by caress. They moderately adapt to stimulus and have short receptive field. Putative mechanosensitive (MS) ion channels expressed in the different tactile receptors are indicated accordingly to preliminary data and summarize present hypothesis under evaluation.

 

A second major population identified concerns the A?-LTMR endings in Awl/Auchenne and zigzag follicles to be compared with the Down hair follicle extensively studied in cat and rabbit. Ginty and collaborators showed that TrkB is expressed at high levels in a subset of medium-diametre DRG neurones. Intracellular recordings using the ex vivo skin-nerve preparation of labeled fibers revealed that they exhibit the physiological properties of fibers previously studied in cat and rabbit: exquisite mechanical sensitivity (Von Frey threshold < 0.07 mN), rapidly adapting responses to suprathreshold stimuli, intermediate conduction velocities (5.8 � 0.9 m/s) and narrow uninflected soma spikes.15 These A?-LTMRs form longitudinal lanceolate endings associated with virtually every zigzag and awl/auchene hair follicle of the trunk [Fig. 1 (A5)].

 

Finally, they showed that the peripheral endings of rapidly adapting A? LTMRs form longitudinal lanceolate endings associated with guard (or tylotrich) and awl/auchene hair follicles [Fig. 1 (A6)].15 In addition, Guard hairs are also associated with a Merkel cell complex forming a touch dome connected to A? slowly adapting LTMR [Fig. 1 (A7)].

 

In summary, virtually all zigzag hair follicles are innervated by both C-LTMR and A?-LTMR lanceolate endings; awl/auchene hairs are triply innervated by A? rapidly adapting-LTMR, A?-LTMR and C-LTMR lanceolate endings; Guard hair follicles are innervated by A? rapidly adapting-LTMR longitudinal lanceolate endings and interact with A? slowly adapting-LTMR of touch dome endings. Thus, each mouse hair follicle receives unique and invariant combinations of LTMR endings corresponding to neurophysiologically distinct mechanosensory end organs. Considering the iterative arrangement of these three hair types, Ginty and collaborators propose that hairy skin consists of iterative repeat of peripheral unit containing, (1) one or two centrally located guard hairs, (2) ~20 surrounding awl/auchenne hairs and (3) ~80 interspersed zigzag hairs [Fig. 2 (C1)].

 

Spinal cord projection. The central projections of A? rapidly adapting-LTMRs, A?-LTMRs and C-LTMRs terminate in distinct, but partially overlapping laminae (II, III, IV) of the spinal cord dorsal horn. In addition, the central terminals of LTMRs that innervate the same or adjacent hair follicles within a peripheral LTMR unit are aligned to form a narrow LTMR column in the spinal cord dorsal horn [Fig. 1 (B1)]. Thus, it appears likely that a wedge, or column of somatotopically organized primary sensory afferent endings in the dorsal horn represents the alignment of the central projections of A?-, A?- and C-LTMRs that innervate the same peripheral unit and detect mechanical stimuli acting upon the same small group of hairs follicles. Based on the numbers of guard, awl/ auchene and zigzag hairs of the trunk and limbs and the numbers of each LTMR subtype, Ginty and collaborators estimate that the mouse dorsal horn contains 2,000�4,000 LTMR columns, which corresponds to the approximate number of peripheral LTMR units.15

 

Furthermore, axones of LTMR subtypes are closely associated with one another, having entwined projections and interdigitated lanceolate endings that innervate the same hair follicle. In addition, because the three hair follicle types exhibit different shapes, sizes and cellular compositions, they are likely to have distinct deflectional or vibrational tuning properties. These findings are consistent with classic neurophysiological measurements in the cat and rabbit indicating that A? RA-LTMRs and A?-LTMRs can be differentially activated by deflection of distinct hair follicle types.16,17

 

In conclusion, touch in hairy skin is the combination of: (1) the relative numbers, unique spatial distributions and distinct morphological and deflectional properties of the three types of hair follicles; (2) the unique combinations of LTMR subtype endings associated with each of the three hair follicle types; and (3) distinct sensitivities, conduction velocities, spike train patterns and adaptation properties of the four main classes of hair-follicle-associated LTMRs that enable the hairy skin mechanosensory system to extract and convey to the CNS the complex combinations of qualities that define a touch.

 

Free-Nerve Endings LTMRs

 

Generally, C-fibers free endings in the skin are HTMRs, but a subpopulation of C-fibers doesn�t respond to noxious touch. This subset of tactile C-fiber (CT) afferents represents a distinct type of unmyelinated, low-threshold mechanoreceptive units existing in the hairy but not glabrous skin of humans and mammals [Fig. 1 (A8)].18,19 CTs are generally associated with the perception of pleasant tactile stimulation in body contact.20,21

 

CT afferents respond to indentation forces in the range 0.3�2.5 mN and are thus as sensitive to skin deformation as many of the A? afferents.19 The adaptation characteristics of CT afferents are thus intermediate in comparison with the slowly and rapidly adapting myelinated mechanoreceptors. The receptive fields of human CT afferents are roughly round or oval in shape. The field consists of one to nine small responsive spots distributed over an area up to 35 mm2.22 The mouse homolog receptors are organized in a pattern of discontinuous patches covering about 50�60% of the area in the hairy skin [Fig. 2 (C2)].23

 

Evidence from patients lacking myelinated tactile afferents indicates that signaling in CT fibers activate the insular cortex. Since this system is poor in encoding discriminative aspects of touch, but well-suited to encoding slow, gentle touch, CT fibers in hairy skin may be part of a system for processing pleasant and socially relevant aspects of touch.24 CT fiber activation may also have a role in pain inhibition and it has recently been proposed that inflammation or trauma may change the sensation conveyed by C-fiber LTMRs from pleasant touch to pain.25,26

 

Which pathway CT-afferents travel is not yet known [Fig. 1 (B2)], but low-threshold tactile inputs to spinothalamic projection cells have been documented,27 lending credence to reports of subtle, contralateral deficits of touch detection in human patients following destruction of these pathways after chordotomy procedures.28

 

LTMRs in Glabrous Skin

 

Merkel cell-neurite complexes and touch dome. Merkel (1875) was the first to give a histological description of clusters of epidermal cells with large lobulated nuclei, making contact with presumed afferent nerve fibers. He assumed that they subserved sense of touch by calling them Tastzellen (tactile cells). In humans, Merkel cell�neurite complexes are enriched in touch sensitive areas of the skin, they are found in the basal layer of the epidermis in fingers, lips and genitals. They also exist in hairy skin at lower density. The Merkel cell�neurite complex consists of a Merkel cell in close apposition to an enlarged nerve terminal from a single myelinated A? fiber [Fig. 1 (C1)] (review in Halata and collaborators).29 At the epidermal side Merkel cell exhibits finger-like processes extending between neighboring keratinocytes [Fig. 1 (C2)]. Merkel cells are keratinocyte-derived epidermal cells.30,31 The term of touch dome was introduced to name the large concentration of Merkel cell complexes in the hairy skin of cat forepaw. A touch dome could have up to 150 Merkel cells innervated by a single A?-fiber and in humans besides A?-fibers, A? and C-fibers were also regularly present.32-34

 

Stimulation of Merkel cell�neurite complexes results in slowly-adapting Type I (SA I) responses, which originate from punctuate receptive fields with sharp borders. There is no spontaneous discharge. These complexes respond to indentation depth of the skin and have the highest spatial resolution (0.5 mm) of the cutaneous mechanoreceptors. They transmit a precise spatial image of tactile stimuli and are proposed to be responsible for shape and texture discrimination [Fig. 2 (B1)]. Mice devoid of Merkel cells cannot detect textured surfaces with their feet while they do so using their whiskers.35

 

Whether the Merkel cell, the sensory neuron or both are sites of mechanotransduction is still a matter of debate. In rats, phototoxic destruction of Merkel cells abolishes SA I response.36 In mice with genetically suppressed-Merkel cells, the SA I response recorded in ex vivo skin/nerve preparation completely disappeared, demonstrating that Merkel cells are required for the proper encoding of Merkel receptor responses.37 However, the mechanical stimulation of isolated Merkel cells in culture by motor driven pressure does not generate mechanically-gated currents.38,39 Keratinocytes may play an important role in the normal functioning of the Merkel cell�neurite complex. The Merkel cell finger-like processes can move with skin deformation and epidermis cell movement, and this may be the first step of mechanical transduction. Clearly, the conditions required to study mechano-sensitivity of Merkel cells have yet to be established.

 

Ruffini endings. Ruffini endings are thin cigar-shaped encapsulated sensory endings connected to A? nerve endings. Ruffini endings are small connective tissue cylinders arranged along dermal collagen strands which are supplied by one to three myelinated nerve fibers of 4�6 �m diametre. Up to three cylinders of different orientation in the dermis may merge to form one receptor [Fig. 1 (C3)]. Structurally, Ruffini endings are similar to Golgi tendon organs. They are broadly expressed in the dermis and have been identified as the slowly adapting type II (SA II) cutaneous mechanoreceptors. Against the background of spontaneous nervous activity, a slowly-adapting regular discharge is elicited by perpendicular low force maintained mechanical stimulation or more effectively by dermal stretch. SA II response originates from large receptive fields with obscure borders. Ruffini receptors contribute to the perception of the direction of object motion through the pattern of skin stretch [Fig. 2 (A2)].

 

In mice, SA I and SA II responses can be separated electrophysiologically in ex-vivo nerve-skin preparation.40 Nandasena and collaborators reported the immunolocalization of aquaporin 1 (AQP1) in the periodontal Ruffini endings of the rat incisors suggesting that AQP1 is involved in the maintenance of the dental osmotic balance necessary for the mechanotransduction.41 The periodontal Ruffini endings also expressed the putative mechanosensitive ion channel ASIC3.42

 

Meissner corpuscles. Meissner corpuscles are localized in the dermal papillae of the glabrous skin, mainly in hand palms and foot soles but also in lips, in tongue, in face, in nipples and in genitals. Anatomically, they consist of an encapsulated nerve ending, the capsule being made of flattened supportive cells arranged as horizontal lamellae embedded in connective tissue. There is one single nerve fiber A? afferents connected per corpuscle [Fig. 1 (C4)]. Any physical deformation of the corpuscle triggers a volley of action potentials that quickly ceases, i.e., they are rapidly adapting receptors. When the stimulus is removed, the corpuscle regains its shape and while doing so produces another volley of action potentials. Due to their superficial location in the dermis, these corpuscles selectively respond to skin motion, tactile detection of slip and vibrations (20�40 Hz). They are sensitive to dynamic skin – for example, between the skin and an object that is being handled [Fig. 2 (A1)].

 

Pacinian corpuscles. Pacinian corpuscles are the deeper mechanoreceptors of the skin and are the most sensitive encapsulated cutaneous mechanoreceptor of skin motion. These large ovoid corpuscles (1 mm in length) made of concentric lamellae of fibrous connective tissue and fibroblasts lined by flat modified Schwann cells are expressed in the deep dermis.43 In the center of the corpuscle, in a fluid-filled cavity called inner bulb, terminates one single A? afferent unmyelinated nerve ending [Fig. 1 (C5)]. They have a large receptive field on the skin�s surface with a particularly sensitive center. The development and function of several rapidly adapting mechanoreceptor types are disrupted in c-Maf mutant mice. In particular, Pacinian corpuscles are severely atrophied.44

 

Pacinian corpuscles display very rapid adaptation in response to the indentation of the skin, the rapidly-adapting II (RA II) nervous discharge that are capable of following high frequency of vibratory stimuli, and allow perception of distant events through transmitted vibrations.45 Pacinian corpuscle afferents respond to sustained indentation with transient activity at the onset and offset of the stimulus. They are also called acceleration detectors because they can detect changes in the strength of the stimulus and, if the rate of change in the stimulus is altered (as happens in vibrations), their response becomes proportional to this change. Pacinian corpuscles sense gross pressure changes and most of all vibrations (150�300 Hz), which they can detect even centimeters away [Fig. 2 (A3)].

 

Tonic response was observed in decapsulated Pacinian corpuscle.46 In addition, intact Pacinian corpuscles respond with sustained activity during constant indentation stimuli, without altering mechanical thresholds or response frequency when GABA-mediated signaling is blocked between lamellate glia and a nerve ending.47 Thus, the non-neuronal components of the Pacinian corpuscle may have dual roles in filtering the mechanical stimulus as well as in modulating the response properties of the sensory neurone.

 

Spinal cord projections. Projections of the A?-LTMRs in the spinal cord are divided in two branches. The principal central branch ascends in the spinal cord in the ipsilateral dorsal columns to the cervical level [Fig. 1 (B3)]. Secondary branches terminate in the dorsal horn in the laminae IV and interfere with the pain transmission, for example. This may attenuate pain as a part of the gate control [Fig. 1 (B4)].48

 

At cervical levels, axones of the principal branch separate in two tracts: the midline tract comprises the gracile fascicle conveying information from the lower half of the body (legs and trunk), and the outer tract comprises the cuneate fascicle conveying information from the upper half of the body (arms and trunk) [Fig. 1 (B5)].

 

Primary tactile afferents make their first synapse with second order neurones at the medulla where fibers from each tract synapse in a nucleus of the same name: the gracile fasciculus axones synapse in the gracile nucleus and the cuneate axones synapse in the cuneate nucleus [Fig. 1 (B6)]. Neurones receiving the synapse provide the secondary afferents and cross the midline immediately to form a tract on the contralateral side of the brainstem�the medial lemniscus�which ascends through the brainstem to the next relay station in the midbrain, specifically, in the thalamus [Fig. 1 (B7)].

 

Molecular specification of LTMRs. Molecular mechanisms controlling the early diversification of LTMRs have been recently partly elucidated. Bourane and collaborators have shown that the neuronal populations expressing the Ret tyrosine kinase receptor (Ret) and its co-receptor GFR?2 in E11�13 embryonic mice DRG selectively coexpress the transcription factor Mafa.49,50 These authors demonstrate that the Mafa/Ret/GFR?2 neurones destined to become three specific types of LTRMs at birth: the SA1 neurones innervating Merkel-cell complexes, the rapidly adapting neurones innervating Meissner corpuscles and the rapidly adapting afferents (RA I) forming lanceolate endings around hair follicles. Ginty and collaborators also report that DRG neurones expressing early-Ret are rapidly adapting mechanoreceptors from Meissner corpuscles, Pacinian corpuscles and lanceolate endings around hair follicles.51 They innervate discrete target zones within the gracile and cuneate nuclei, revealing a modality-specific pattern of mechanosensory neurone axonal projections within the brainstem.

 

Exploration of human skin mechanoreceptors. The technique of �microneurography� described by Hagbarth and Vallbo in 1968 has been applied to study the discharge behavior of single human mechanosensitive endings supplying muscle, joint and skin (see for review Macefield, 2005).52,53 The majority of human skin microneurography studies have characterized the physiology of tactile afferents in the glabrous skin of the hand. Microelectrode recordings from the median and ulnar nerves in human subjects have revealed touch sensation generated by the four classes of LTMRs: Meissner afferents are particularly sensitive to light stroking across the skin, responding to local shear forces and incipient or overt slips within the receptive field. Pacinian afferents are exquisitively sensitive to brisk mechanical transients. Afferents respond vigorously to blowing over the receptive field. A Pacinian corpuscle located in a digit will usually respond to tapping the table supporting the arm. Merkel afferents characteristically have a high dynamic sensitivity to indentation stimuli applied to a discrete area and often respond with an off-discharge during release. Although the Ruffini afferents do respond to forces applied normally to the skin, a unique feature of SA II afferents is their capacity to respond also to lateral skin stretch. Finally, hair units in the forearm have large ovoid or irregular receptive fields composed of multiple sensitive spots that corresponded to individual hairs (each afferent supply ~20 hairs).

 

Mechanical Sensitivity of Keratinocytes

 

Any mechanical stimulus on the skin must be transmitted through keratinocytes that form the epidermis. These ubiquitous cells may perform signaling functions in addition to their supportive or protective roles. For example, keratinocytes secrete ATP, an important sensory signaling molecule, in response to mechanical and osmotic stimuli.54,55 The release of ATP induces intracellular calcium increase by autocrine stimulation of purinergic receptors.55 Furthermore, there is evidence that hypotonicity activates the Rho-kinase signaling pathway and the subsequent F-actin stress fiber formation suggesting that the mechanical deformation of the keratinocytes may mechanically interfere with the neighbor cells such as Merkel cells for innocuous touch and C-fiber free endings for noxious touch [Fig. 1 (C6)].56,57

 

Noxious Touch

 

High threshold mechanoreceptors (HTMRs) are epidermal C- and A? free nerve-endings. They are not associated with specialized structures and are observed in both hairy skin [Fig. 1 (A9)] and glabrous skin [Fig. 1(C7)]. However, the term of free nerve-ending has to be considered prudently since nerve endings are always in close apposition with keratinocyte or Langherans� cell or melanocytes. Ultrastructural analysis of nerve endings reveals the presence of rough endoplasmic reticulum, abundant mitochondria and dense-core vesicle. Adjacent membranes of epidermal cells are thickened and resembling post-synaptic membrane in nervous tissues. Note that the interactions between nerve endings and epidermal cells may be bidirectional since epidermal cells may release mediators as ATP, interleukine (IL6, IL10) and bradykinin and conversely peptidergic nerve endings may release peptides such as CGRP or substance P acting on epidermal cells. HTMRs comprise mechano-nociceptors excited only by noxious mechanical stimuli and polymodal nociceptors that also respond to noxious heat and exogenous chemical [Fig. 2 (B2)].58

 

HTMR afferent fibers terminate on projection neurones in the dorsal horn of the spinal cord. A?-HTMRs contact second order neurones predominantly in the lamina I and V, whereas C-HTMRs terminate in the lamina II [Fig. 1 (B8)]. Second order nociceptive neurones project to the controlateral side of the spinal cord and ascend in the white matter, forming the anterolateral system. These neurones terminate mainly in the thalamus [Fig. 1 (B9 and B10)].

 

Mechano-Currents in Somatosensory Neurones

 

The mechanisms of slow or rapid adaptation of mechanoreceptors are not yet elucidated. It is not clear to what extent mechanoreceptor adaptation is provided by the cellular environment of the sensory nerve ending, the intrinsic properties of the mechanically-gated channels and the properties of the axonal voltage-gated ion channels in sensory neurones (Fig. 2). However, recent progress in the characterization of mechanically-gated currents has demonstrated that different classes of mechanosensitive channels exist in DRG neurones and may explain some aspects of the adaptation of mechanoreceptors.

 

In vitro recording in rodents has shown that the soma of DRG neurons is intrinsically mechanosensitive and express cationic mechano-gated currents.59-64 Gadolinium and ruthenium red fully block mechanosensitive currents, whereas external calcium and magnesium, at physiological concentrations, as well as amiloride and benzamil, cause partial block.60,62,63 FM1-43 acts as a lasting blocker, and the injection of FM1-43 into the hind paw of mice decreases pain sensitivity in the Randall�Selitto test and increases the paw withdrawal threshold assessed with von Frey hairs.65

 

In response to sustained mechanical stimulation, mechanosensitive currents decline through closure. Based on the time constants of current decay, four distinct types of mechanosensitive currents have been distinguished: rapidly adapting currents (~3�6 ms), intermediately adapting currents (~15�30 ms), slowly adapting currents (~200�300 ms) and ultra-slowly adapting currents (~1000 ms).64 All these currents are present with variable incidence in rat DRG neurones innervating the glabrous skin of the hindpaw.64

 

The mechanical sensitivity of mechanosensitive currents can be determined by applying a series of incremental mechanical stimuli, allowing for relatively detailed stimulus-current analysis.66 The stimulus�current relationship is typically sigmoidal, and the maximum amplitude of the current is determined by the number of channels that are simultaneously open.64,67 Interestingly, the rapidly adapting mechanosensitive current has been reported to display low mechanical threshold and half-activation midpoint compared with the ultra-slowly adapting mechanosensitive current.63,65

 

Sensory neurones with non-nociceptive phenotypes preferentially express rapidly adapting mechanosensitive currents with lower mechanical threshold.60,61,63,64,68 Conversely, slowly and ultra-slowly adapting mechanosensitive currents are occasionally reported in putative non-nociceptive cells.64,68 This prompted suggestion that these currents might contribute to the different mechanical thresholds seen in LTMRs and HTMRs in vivo. Although these in vitro experiments should be taken with caution, support for the presence in the soma of the DRG neurones of low- and high-threshold mechanotransducers was also provided by radial stretch-based stimulation of cultured mouse sensory neurones.69 This paradigm revealed two main populations of stretch-sensitive neurones, one that responds to low stimulus amplitude and another one that selectively responds to high stimulus amplitude.

 

These results have important, yet speculative, mechanistic implications: the mechanical threshold of sensory neurones might have little to do with the cellular organization of the mechanoreceptor but may lie in the properties of the mechanically-gated ion channels.

 

The mechanisms that underlie desensitization of mechanosensitive cation currents in rat DRG neurones have been recently unraveled.64,67 It results from two concurrent mechanisms that affect channel properties: adaptation and inactivation. Adaptation was first reported in auditory hair cell studies. It can be described operationally as a simple translation of the transducer channel�s activation curve along the mechanical stimulus axis.70-72 Adaptation allows sensory receptors to maintain their sensitivity to new stimuli in the presence of an existing stimulus. However, a substantial fraction of mechanosensitive currents in DRG neurones cannot be reactivated following conditioning mechanical stimulation, indicating inactivation of some transducer channels.64,67 Therefore, both inactivation and adaptation act in tandem to regulate mechanosensitive currents. These two mechanisms are common to all mechanosensitive currents identified in rat DRG neurones, suggesting that related physicochemical elements determine the kinetics of these channels.64

 

In conclusion, determining the properties of endogenous mechanosensitive currents in vitro is crucial in the quest to identify transduction mechanisms at the molecular level. The variability observed in the mechanical threshold and the adapting kinetics of the different mechanically-gated currents in DRG neurones suggest that intrinsic properties of ion channels may explain, at least in part, mechanical threshold and adaptation kinetics of the mechanoreceptors described in the decades 1960�80 using ex vivo preparations.

 

Putative Mechanosensitive Proteins

 

Mechanosensitive ion currents in somatosensory neurones are well characterized, by contrast, little is known about the identity of molecules that mediate mechanotransduction in mammals. Genetic screens in Drosophila and C. elegans have identified candidate mechanotransduction molecules, including the TRP and degenerin/epithelial Na+ channel (Deg/ENaC) families.73 Recent attempts to elucidate the molecular basis of mechanotransduction in mammals have largely focused on homologs of these candidates. Additionally, many of these candidates are present in cutaneous mechanoreceptors and somatosensory neurones (Fig. 2).

 

Acid-Sensing Ion Channels

 

ASICs belong to a proton-gated subgroup of the degenerin�epithelial Na+ channel family.74 Three members of the ASIC family (ASIC1, ASIC2 and ASIC3) are expressed in mechanoreceptors and nociceptors. The role of ASIC channels has been investigated in behavioral studies using mice with targeted deletion of ASIC channel genes. Deletion of ASIC1 does not alter the function of cutaneous mechanoreceptors but increases mechanical sensitivity of afferents innervating the gut.75 ASIC2 knockout mice exhibit a decreased sensitivity of rapidly adapting cutaneous LTMRs.76 However, subsequent studies reported a lack of effects of knocking out ASIC2 on both visceral mechano-nociception and cutaneous mechanosensation.77 ASIC3 disruption decreases mechano sensitivity of visceral afferents and reduces responses of cutaneous HTMRs to noxious stimuli.76

 

The Transient Receptor Channel

 

THE TRP superfamily is subdivided into six subfamilies in mammals.78 Nearly all TRP subfamilies have members linked to mechanosensation in a variety of cell systems.79 In mammalian sensory neurones, however, TRP channels are best known for sensing thermal information and mediating neurogenic inflammation, and only two TRP channels, TRPV4 and TRPA1, have been implicated in touch responsiveness. Disrupting TRPV4 expression in mice has only modest effects on acute mechanosensory thresholds, but strongly reduces sensitivity to noxious mechanical stimuli.80,81 TRPV4 is a crucial determinant in shaping the response of nociceptive neurones to osmotic stress and to mechanical hyperalgesia during inflammation.82,83 TRPA1 seems to have a role in mechanical hyperalgesia. TRPA1-deficient mice exhibit pain hypersensitivity. TRPA1 contributes to the transduction of mechanical, cold and chemical stimuli in nociceptor sensory neurones but it appears that is not essential for hair-cell transduction.84,85

 

There is no clear evidence indicating that TRP channels and ASICs channels expressed in mammals are mechanically gated. None of these channels expressed heterologously recapitulates the electrical signature of mechanosensitive currents observed in their native environment. This does not rule out the possibility that ASICs and TRPs channels are mechanotransducers, given the uncertainty of whether a mechanotransduction channel may function outside of its cellular context (see section on SLP3).

 

Piezo Proteins

 

Piezo protiens have been recently identified like as promising candidates for mechanosensing proteins by Coste and collaborators.86,87 Vertebrates have two Piezo members, Piezo 1 and Piezo 2, previously known as FAM38A and FAM38B, respectively, which are well conserved throughout multi cellular eukaryotes. Piezo 2 is abundant in DRGs, whereas Piezo 1 is barely detectable. Piezo-induced mechanosensitive currents are prevented inhibited by gadolinium, ruthenium red and GsMTx4 (a toxin from the tarantula Grammostola spatulata).88 Expression of Piezo 1 or Piezo 2 in heterologous systems produces mechanosensitive currents, the kinetics of inactivation of Piezo 2 current being faster than Piezo 1. Similar to endogenous mechanosensitive currents, Piezo-dependent currents have reversal potentials around 0 mV and are cation no selective, with Na+, K+, Ca2+ and Mg2+ all permeating the underlying channel. Likewise, piezo-dependent currents are regulated by membrane potential, with a marked slowing of current kinetics at depolarized potentials.86

 

Piezo proteins are undoubtedly mechanosensing proteins and share many properties of rapidly adapting mechanosensitive currents in sensory neurones. Treatment of cultured DRG neurones with Piezo 2 short interfering RNA decreased the proportion of neurones with rapidly adapting current and decreased the percentage of mechanosensitive neurones.86 Transmembrane domains are located throughout the piezo proteins but no obvious pore-containing motifs or ion channel signatures have been identified. However, mouse Piezo 1 protein purified and reconstituted into asymmetric lipid bilayers and liposome forms ion channels sensitive to ruthenium red.87 An essential step in validating mechanotransduction through Piezo channels is to use in vivo approaches to determine the functional importance in touch signaling. Information was given in Drosophila where deletion of the single Piezo member reduced mechanical response to noxious stimuli, without affecting normal touch.89 Although their structure remains to be determined, this novel family of mechanosensitive proteins is a promising subject for future research, beyond the border of touch sensation. For exemple, a recent study on patients with anemia (hereditary xerocytosis) shows the role of Piezo 1 in maintaining erythrocyte volume homeostasis.90

 

Transmembrane Channel-Like (TMC)

 

A recent study indicates that two proteins, TMC1 and TMC2, are necessary for hair cell mechanotransduction.91 Hereditary deafness due to TMC1 gene mutation was reported in human and mice.92,93 Presence of these channels had not yet been shown in the somatosensory system, but it seems to be a good lead to investigate.

 

Stomatin-Like Protein 3 (SLP3)

 

Additionally to the transduction channels, some accessory proteins linked to the channel have been shown to play a role in touch sensivity. SLP3 is expressed in mammalian DRG neurones. Studies using mutant mice lacking SLP3 had shown change in mechanosensation and mechanosentive currents.94,95 SLP3 precise function remains unknown. It may be a linker between the mechanosensitive channel and the underlying microtubules, as proposed for its C. elegans homolog MEC2.96 Recently GR. Lewin lab has suggested that a tether is synthesized by DRG sensory neurones and links mechanosensitive ion channel to the extracellular matrix.97 Disrupting the link abolishes the RA-mechanosensitive current suggesting that some ion channels are mechanosensitive only when tethered. RA-mechanosensitive currents are also inhibited by laminin-332, a matrix protein produced by keratinocytes, reinforcing the hypothesis of a modulation of the mechanosensitive current by extracellular proteins.98

 

K+ Channel Subfamily

 

In parallel to cationic depolarizing mechanosensitive currents, the presence of repolarizing mechanosensitive K+ currents is under investigation. K+ channels in mechanosensitive cells can step in the current balance and contribute to define the mechanical threshold and the time course of adaptation of mechanoreceptors.

 

KCNK members belong to the two-pore domain K+ channel (K2P) family.99,100 The K2P display a remarkable range of regulation by cellular, physical and pharmacological agents, including pH changes, heat, stretch and membrane deformation. These K2P are active at resting membrane potential. Several KCNK subunits are expressed in somatosensory neurones.101 KCNK2 (TREK-1), KCNK4 (TRAAK) and TREK-2 channels are among the few channels for which a direct mechanical gating by membrane stretch has been shown.102,103

 

Mice with a disrupted KCNK2 gene displayed an enhanced sensitivity to heat and mild mechanical stimuli but a normal withdrawal threshold to noxious mechanical pressure applied to the hindpaw using the Randall�Selitto test.104 KCNK2-deficient mice also displays increased thermal and mechanical hyperalgesia in inflammatory conditions. KCNK4 knockout mice were hypersensitive to mild mechanical stimulation, and this hypersensitivity was increased by additional inactivation of KCNK2.105 Increased mechanosensitivity of these knockout mice could mean that stretch normally activates both depolarizing and repolarizing mechanosensitive currents in a coordinated way, similarly to the unbalance of depolarizing and repolarizing voltage-gated currents.

 

KCNK18 (TRESK) is a major contributor to the background K+ conductance that regulates the resting membrane potential of somatosensory neurones.106 Although it is not known if KCNK18 is directly sensitive to mechanical stimulation, it may play a role in mediating responses to light touch, as well as painful mechanical stimuli. KCNK18 and to a lesser extent KCNK3, are proposed to be the molecular target of hydroxy-?-sanshool, a compound found in Schezuan peppercorns that activates touch receptors and induces a tingling sensation in humans.107,108

 

The voltage dependent K+ channel KCNQ4 (Kv7.4) is crucial for setting the velocity and frequency preference of a subpopulation of rapidly adapting mechanoreceptors in both mice and humans. Mutation of KCNQ4 has been initially associated with a form of hereditary deafness. Interestingly a recent study localizes KCNQ4 in the peripheral nerve endings of cutaneous rapidly adapting hair follicle and Meissner corpuscle. Accordingly, loss of KCNQ4 function leads to a selective enhancement of mechanoreceptor sensitivity to low-frequency vibration. Notably, people with late-onset hearing loss due to dominant mutations of the KCNQ4 gene show enhanced performance in detecting small-amplitude, low-frequency vibration.109

 

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Dr. Alex Jimenez’s Insight

Touch is considered to be one of the most complex senses in the human body, particularly because there is no specific organ in charge of it. Instead, the sense of touch occurs through sensory receptors, known as mechanoreceptors, which are found across the skin and respond to mechanical pressure or distortion. There are four main types of mechanoreceptors in the glabrous, or hairless, skin of mammals: lamellar corpuscles, tactile corpuscles, Merkel nerve endings and bulbous corpuscles. Mechanoreceptors function in order to allow the detection of touch, in order to monitor the position of the muscles, bones and joints, known as proprioception, and even to detect sounds and the motion of the body. Understanding the mechanisms of structure and function of these mechanoreceptors is a fundamental element in the utilization of treatments and therapies for pain management.

 

Conclusion

 

Touch is a complex sense because it represents different tactile qualities, namely, vibration, shape, texture, pleasure and pain, with different discriminative performances. Up to now, the correspondence between a touch-organ and the psychophysical sense was correlative and class-specific molecular markers are just emerging. The development of rodent tests matching the diversity of touch behavior is now required to facilitate future genomics identification. The use of mice that lack specific subsets of sensory afferent types will greatly facilitate identification of mechanoreceptors and sensory afferent fibers associated with a particular touch modality. Interestingly, a recent paper opens the important question of the genetic basis of mechanosensory traits in human and suggests that single gene mutation could negatively influence touch sensitivity.110 This underlines that the pathophysiology of the human touch deficit is in a large part unknown and would certainly progress by identifying precisely the subset of sensory neurones linked to a touch modality or a touch deficit.

 

In return, progress has been made to define the biophysical properties of the mechano-gated currents.64 The development of new techniques in recent years, allowing monitoring of membrane tension changes, while recording mechano-gated current, has proved valuable experimental method to describe mechanosensitive currents with rapid, intermediate and slow adaptation (reviewed in Delmas and collaborators).66,111 The future will be to determine the role of the current properties in the mechanisms of adaptation of functionally diverse mechanoreceptors and the contribution of mechanosensitive K+ currents to the excitability of LTMRs and HTMRs.

 

The molecular nature of mechano-gated currents in mammals is also a future promising research topic. Future research will progress in two perspectives, first to determine the role of accessory molecule that tether channels to the cytoskeleton and would be required to confer or regulate mechanosensitivity of ion channels of the like of TRP and ASIC/EnaC families. Second, to investigate the large and promising area of the contribution of the Piezo channels by answering key questions, relative to the permeation and gating mechanisms, the subset of sensory neurones and touch modalities involving Piezo and the role of Piezo in non neuronal cells associated with mechanosensation.

 

The sense of touch, in comparison to that of sight, taste, sound and smell, which utilize specific organs to process these sensations, can occur all throughout the body through tiny receptors known as mechanoreceptors. Different types of mechanoreceptors can be found in various layers of the skin, where they can detect a wide array of mechanical stimulation. The article above describes specific highlights which demonstrate the progress of structural and functional mechanisms of mechanoreceptors associated with the sense of touch. Information referenced from the National Center for Biotechnology Information (NCBI). The scope of our information is limited to chiropractic as well as to spinal injuries and conditions. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at�915-850-0900�.

 

Curated by Dr. Alex Jimenez

 

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Additional Topics: Back Pain

 

Back pain is one of the most prevalent causes for disability and missed days at work worldwide. As a matter of fact, back pain has been attributed as the second most common reason for doctor office visits, outnumbered only by upper-respiratory infections. Approximately 80 percent of the population will experience some type of back pain at least once throughout their life. The spine is a complex structure made up of bones, joints, ligaments and muscles, among other soft tissues. Because of this, injuries and/or aggravated conditions, such as herniated discs, can eventually lead to symptoms of back pain. Sports injuries or automobile accident injuries are often the most frequent cause of back pain, however, sometimes the simplest of movements can have painful results. Fortunately, alternative treatment options, such as chiropractic care, can help ease back pain through the use of spinal adjustments and manual manipulations, ultimately improving pain relief.

 

 

 

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EXTRA IMPORTANT TOPIC: Low Back Pain Management

 

MORE TOPICS: EXTRA EXTRA:�Chronic Pain & Treatments

 

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Close Accordion
MechanoReceptive Pain: Peripheral And Central Mechanisms

MechanoReceptive Pain: Peripheral And Central Mechanisms

Mechanoreceptive Pain: According to the CDC, �more than 50% of U.S. adults (125 million) had a musculoskeletal pain disorder in 2012.�

�More than 40% of adults with a musculoskeletal pain disorder used a complementary health approach for any reason in 2012. This was significantly higher than use among persons without a musculoskeletal pain disorder (24.1%). Use of complementary health approaches for any reason among persons with neck pain or problems was more than twice as high as use among persons without these problems.�

mechanoreceptive el paso tx.

Retrieved from: www.cdc.gov/nchs/data/nhsr/nhsr098.pdf

UNDERSTANDING PAIN IS IMPORTANT

�Among adults with a musculoskeletal pain disorder, use of any complementary health approach was highest among those with neck pain or problems (50.6%), followed by persons with other musculoskeletal problems (46.2%).”

�Use of complementary health approaches for any reason among persons with neck pain or problems was more than twice as high as use among persons without these problems.�

mechanoreceptive el paso tx.

Retrieved from: www.cdc.gov/nchs/data/nhsr/nhsr098.pdf

WHAT IS A MECHANORECEPTOR?

  • Mechanoreceptors are sensory receptors that respond to mechanical pressure or distortion.
  • These include cutaneous receptors for touch, receptors that monitor muscle length and tension, auditory and vestibular receptors and others.

mechanoreceptive el paso tx.GATE CONTROL THEORY OF PAIN

  • Non-painful input closes the gates to painful input.
  • This prevents pain sensations from traveling to higher cortical levels
  • Small diameter afferents (pain) impede inhibition of pain
  • Large diameter afferents (vibration) tend to excite inhibition of pain.

mechanoreceptive el paso tx.

  • This theory asserts non-nociceptive fibers can interfere with signals from pain fibers, therefore, inhibiting pain.
  • Large-diameter A? fibers are nonnociceptive (do not transmit pain stimuli) and inhibit the effects of firing by A? and C fibers.

mechanoreceptive el paso tx.DORSAL COLUMN MEDIAL LEMNISCAL PATHWAY

mechanoreceptive el paso tx.UTILIZATION OF PERIPHERAL MECHANORECEPTORS TO ALTER PAIN PERCEPTION

HOW CAN WE HELP?

mechanoreceptive el paso tx.

 

mechanoreceptive el paso tx.

WITHDRAWAL REFLEX

  • An excited afferent neuron stimulates excitatory interneurons that in turn stimulate the efferent motor neurons supplying the biceps, the muscle in the arm that flexes (bends) the elbow joint. Contraction of the biceps pulls the hand away from the hot stove.
  • The afferent neuron also stimulates inhibitory interneurons that in turn inhibit the efferent neurons supplying the triceps to prevent it from contracting. This type of neuronal connection involving stimulation of the nerve supply to one muscle and simultaneous inhibition of the nerves to its antagonistic muscle is known as reciprocal inhibition.
  • The afferent neuron still stimulates other interneurons that carry the signal up the spinal cord to the brain via an ascending pathway. Only when the impulse reaches the sensory area of the cortex is the person aware of the pain, its location and the type of stimulus. Moreover, when the impulse reaches the brain, the information can be stored as memory and the person can think about what happened.

mechanoreceptive el paso tx.

RECEPTOR BASED THERAPY

Adjustments
  • Activation of joint mechanoreceptors through chiropractic adjustments can modulate and �overshadow� the brains perception of smaller diameter fibers.
  • Repetition of activation of joint mechanoreceptors can create positive plasticity in afferent pathways.
  • Positive plasticity can shut down pain

mechanoreceptive el paso tx.

Vibration
  • Vibratory stimulation at specific frequencies can alter pain perception
  • Repetition of activation of Merkel�s discs and Meissner�s corpuscles can create positive plasticity in afferent pathways.
  • Again, positive plasticity can shut down pain

mechanoreceptive el paso tx.VIBRATION

  • �This type of device applies sinusoidal vibrations and offers continuous selectable amplitude of 0-5.2mm depending on the foot position and a selectable frequency of 5-30Hz.�
  • �WBV training seems to be an effective, safe, and suitable intervention for seated working employees with chronic low-back pain.�

mechanoreceptive el paso tx.

 

  • �Homotopic vibro-tactile stimulation resulted in 40% heat pain reductions in all subject groups. Distraction did not seem to affect experimental pain ratings.�
  • �Vibro-tactile stimulation effectively recruited analgesic mechanisms not only in NC but also in patients with chronic musculoskeletal pain, including FM.�

mechanoreceptive el paso tx.LIGHT TOUCH

  • �In total, 44 healthy volunteers experienced heat pain and CT optimal (slow brushing) and CT sub-optimal (fast brushing or vibration) stimuli. Three different experimental paradigms were used: Concurrent application of heat pain and tactile (slow brushing or vibration) stimulation; Slow brushing, applied for variable duration and intervals, preceding heat pain; Slow versus fast brushing preceding heat pain.�

mechanoreceptive el paso tx.

  • In humans, the main brain areas receiving C- LTMR information belong to the somatosensory system and affect processing brain networks like the contralateral posterior insular cortex or the medial prefrontal cortex. The intensity of CT targeted touch is encoded in the primary and secondary somatosensory cortex (S1 contralateral, S2 bilateral), whereas the pleasantness is encoded in the anterior cingulate cortex. C-LTMRs also activate regions involved in reward processing (putamen and orbitofrontal cortex) and in processing of social stimuli (posterior superior temporal sulcus).

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mechanoreceptive el paso tx.

 

mechanoreceptive el paso tx.

 

mechanoreceptive el paso tx.

 

mechanoreceptive el paso tx.

EVERYTHING PERIPHERAL HAS A CENTRAL CONSEQUENCE

mechanoreceptive el paso tx.

 

mechanoreceptive el paso tx.

 

mechanoreceptive el paso tx.

 

mechanoreceptive el paso tx.CASE STUDY

  • 47-year-old male suffered left CVA in October of 2017.
  • Has not moved the right side of his body since the accident.
  • Presented to our clinic because he wants to �get back to it.�

mechanoreceptive el paso tx.PHYSICAL EXAMINATION HIGHLIGHTS

  • Dysarthria
  • Altered pain perception
  • Difficulty with simple math
  • Flaccid on RUE and RLE

mechanoreceptive el paso tx.PHYSICAL EXAMINATION HIGHLIGHTS

  • Patient had no movement until we began testing sensation and reflexes:

mechanoreceptive el paso tx.

ALLODYNIA:�Refers to central pain sensitization ( increased response of neurons) following normally non-painful, often repetitive stimulation.

  • Allodynia can lead to the triggering of a pain response from stimuli, which does not normally provoke pain.
  • Temperature or physical stimuli can provoke allodynia, which may feel like a burning sensation and it often occurs after injury to a site.
  • Alldynia is different from Hyperalgesia, an extreme, exaggerated reaction to a stimulus, which is normally painful.

THERAPEUTIC INTERVENTIONS

  • Vibration
  • Light Touch
  • Acupressure
  • Acoustic Frequencies
  • Adjustments!

mechanoreceptive el paso tx.AFTER TWO DAYS

mechanoreceptive el paso tx.

mechanoreceptive el paso tx.

Mechanoreceptive Pain & Receptor Based Therapy

Understanding Abnormalities of the Pain System in El Paso, Tx

Understanding Abnormalities of the Pain System in El Paso, Tx

Why does localized damage or injury caused by trauma lead to chronic, intractable pain in certain patients? What’s in charge of the translation of local injury with acute pain into a chronic pain condition? Why does some pain respond to anti-inflammatory drugs and/or medications, whereas other forms of pain require opiates?

 

Pain is an intricate process involving both the peripheral nervous system (PNS) and the central nervous system (CNS). Tissue injury triggers the PNS, which transmits signals via the spinal cord into the brain, in which pain perception occurs. However, what causes the intense experience of pain to develop into an unremitting phenomenon? Can anything be done to prevent it? Evidence indicates that chronic pain results from a combination of mechanisms, such as neurological “memories” of preceding pain.

 

Nociception: The Simplest Pathway

 

Acute or nociceptive pain is characterized as the regular experience of discomfort which occurs in response to very basic damage or injury. It is protective, warning us to move away from the origin of the insult and take care of the trauma. The mechanisms that create nociceptive pain include transduction, which extends the external traumatic stimulation into electrical activity in specialized nociceptive primary afferent nerves. The afferent nerves then conduct the sensory information from the PNS to the CNS.

 

In the CNS, the pain data is transmitted by the primary sensory neurons into central projection cells. After the information is transferred to all those areas of the brain which are responsible for our perception, the actual sensory experience happens. Nociceptive pain is a relatively simple reaction to a particularly simple, acute stimulus. But the mechanics in charge of nociceptive pain cannot identify phenomena, such as pain that persists despite removal or healing of the stimulation, such as in the instance of phantom limb pain.

 

Pain and the Inflammatory Response

 

In circumstances of more severe injury, such as surgical wounds, tissue damage may stimulate an inflammatory reaction. However, other conditions, especially arthritis, can also be characterized by continuing cases of inflammation associated with intense pain symptoms. The mechanisms for this type of pain related to tissue damage and an inflammatory response are different from early-warning nociceptive pain.

 

Observing the incision or site of other damage or injury, a cascade of hyperexcitable events occur in the nervous system. This bodily “wind-up” phenomenon begins at the skin, where it is potentiated along the peripheral nerves, and culminates at a hypersensitivity response along the spinal cord (dorsal horn) and the brain. Inflammatory cells then surround the regions of tissue damage and also produce cytokines and chemokines, substances which are intended to mediate the process of healing and tissue regeneration. But, these agents may also be considered irritants and adjust the properties of the primary sensory neurons surrounding the area of trauma.

 

Thus, the major factors which trigger inflammatory pain include damage to the high-threshold nociceptors, known as peripheral sensitization, changes and alterations of the neurons in the nervous system, and the amplification of the excitability of neurons within the CNS. This represents central sensitization and is accountable for hypersensitivity, where areas adjacent to those of the true injury will experience pain as if these were injured. These tissues can also react to stimulation which normally doesn’t create pain, such as a touch, wearing clothing, light pressure, or even brushing your own hair, as if they were truly painful, referred to as allodynia.

 

Peripheral and Central Sensitization (Video)

 

 

Other Mechanisms of Pain

 

Neuropathic pain results from damage or injury to the nervous system, such as carpal tunnel syndrome, postherpetic neuralgia and diabetic neuropathy. Although some of the mechanisms which seem to cause neuropathic pain overlap with those responsible for inflammatory pain, many of them are different, and thus will need a different approach towards their management.

 

The process of peripheral and central sensitization is maintained, at least theoretically and experimentally, during the excitatory neurotransmitter, glutamate, which is believed to be released when the N-methyl-D-aspartate (NMDA) receptor is activated.

 

The nervous system is made up of either inhibitory or excitatory neurotransmitters. Most of what permits our nervous system to respond appropriately to damage or injury is the fine-tuning or inhibition of a variety of processes. The overexcitation of the nervous system is seen to be an issue in a number of different disorders. For instance, overactivation of an NMDA receptor can also be related to affective disorders, sympathetic abnormalities, and even opiate tolerance.

 

Even ordinary nociceptive pain, to some degree, activates the NMDA receptor and is believed to lead to glutamate release. Nonetheless, in neuropathic pain, oversensitivity to the NMDA receptor is key.

 

With other types of chronic pain, such as fibromyalgia and tension-type headaches, some of the mechanisms active in inflammatory and neuropathic pain may also create similar abnormalities in the pain system, including central sensitization, higher excitability of the somatosensory pathways, and reductions in central nervous system inhibitory mechanisms.

 

Peripheral Sensitization

 

Cyclo-oxygenase (COX) also plays an essential function in both peripheral and central sensitizations. COX-2 is one of the enzymes which are induced during the inflammatory process; COX-2 converts arachidonic acid into prostaglandins, which increase the sensitivity of peripheral nociceptor terminals. Virtually, peripheral inflammation also causes COX-2 to be produced from the CNS. Signals from peripheral nociceptors are partially responsible for this upregulation, but there also seems to be a humoral component to the transduction of the pain signals across the blood-brain barrier.

 

For instance, in experimental models, COX-2 is generated from the CNS even if animals receive a sensory nerve block prior to peripheral inflammatory stimulation. The COX-2 that is expressed over the dorsal horn neurons of the spinal cord releases prostaglandins, which act on the central terminals, or the presynaptic terminals of nociceptive sensory fibers, to increase transmitter release. Additionally, they act postsynaptically on the dorsal horn neurons to produce direct depolarization. And finally, they inhibit the activity of glycine receptor, and this is an inhibitory transmitter. Therefore, the prostaglandins create an increase in excitability of central neurons.

 

Peripheral and Central Sensitization | El Paso, TX Chiropractor

 

Brain Plasticity and Central Sensitization

 

Central sensitization describes changes which happen in the brain in reaction to repeated nerve stimulation. After repeated stimuli, amounts of hormones and brain electric signals change as neurons develop a “memory’ for reacting to those signs. Constant stimulation creates a more powerful brain memory, so the brain will respond more rapidly and effectively when undergoing the identical stimulation in the future. The consequent modifications in brain wiring and reaction are referred to as neural plasticity, which describe the capability of the brain to alter itself readily, or central sensitization. Therefore, the brain is activated or sensitized by previous or repeated stimuli to become more excitable.

 

The fluctuations of central sensitization occur after repeated encounters with pain. Research in animals indicates that repeated exposure to a painful stimulation will change the animal’s pain threshold and lead to a stronger pain response. Researchers think that these modifications can explain the persistent pain that could occur even after successful back surgery. Although a herniated disc may be removed from a pinched nerve, pain may continue as a memory of the nerve compression. Newborns undergoing circumcision without anesthesia will react more profoundly to future painful stimulation, such as routine injections, vaccinations, and other painful processes. These children haven’t only a higher hemodynamic reaction, known as tachycardia and tachypnea, but they will also develop enhanced crying too.

 

This neurological memory of pain was studied extensively. In a report on his previous research studies, Woolf noted that the improved reflex excitability following peripheral tissue damage or injury doesn’t rely on continuing peripheral input signals; rather, hours after a peripheral trauma, spinal dorsal horn neuron receptive fields continued to enlarge. Researchers also have documented the significance of the spinal NMDA receptor to the induction and maintenance of central sensitization.

 

Mechanism of Central Sensitization | El Paso, TX Chiropractor

 

Cortical Reorganization | El Paso, TX Chiropractor

 

Significance for Pain Management

 

Once central sensitization is established, bigger doses of analgesics are often required to suppress it. Preemptive analgesia, or therapy before pain progresses, may lower the effects of all of these stimulation on the CNS. Woolf demonstrated that the morphine dose required to stop central hyperexcitability, given before short noxious electrical stimulation in rats, was one tenth the dose required to abolish activity after it had grown. This translates to clinical practice.

 

In a clinical trial of 60 patients undergoing abdominal hysterectomy, individuals who received 10 mg of morphine intravenously at the time of induction of anesthesia required significantly less morphine for postoperative pain control. Furthermore, pain sensitivity around the wound, referred to as secondary hyperalgesia, was also reduced in the morphine pretreated group. Preemptive analgesia was used with comparable success in an assortment of surgical settings, including prespinal operation and postorthopaedic operation.

 

A single dose of 40 or 60 mg/kg of rectal acetaminophen has a clear morphine-sparing effect in day-case surgery in children, if administered in the induction of anesthesia. Furthermore, children with sufficient analgesia with acetaminophen experienced significantly less postoperative nausea and vomiting.

 

NMDA receptor antagonists have imparted postoperative analgesia when administered preoperatively. Various reports exist in the literature supporting the use of ketamine and dextromethorphan in the preoperative period. In patients undergoing anterior cruciate ligament reconstruction, 24-hour patient-controlled analgesia opioid consumption was significantly less in the preoperative dextromethorphan category versus the placebo group.

 

In double-blind, placebo-controlled research studies, gabapentin was indicated as a premedicant analgesic for patients undergoing mastectomy and hysterectomy. Preoperative oral gabapentin reduced pain scores and postoperative analgesic consumption without gap in side effects as compared with placebo.

 

Preoperative administration of nonsteroidal anti-inflammatory drugs (NSAIDs) has demonstrated a significant decrease in opioid use postoperatively. COX-2s are preferable due to their relative lack of platelet effects and significant gastrointestinal safety profile when compared with conventional NSAIDs. Celecoxib, rofecoxib, valdecoxib, and parecoxib, outside the United States, administered preoperatively reduce postoperative narcotic use by more than 40 percent, with many patients using less than half of the opioids compared with placebo.

 

Blocking nerve conduction in the preoperative period appears to prevent the development of central sensitization. Phantom limb syndrome (PLS) has been attributed to a spinal wind-up phenomenon.�Patients with amputation
often have burning or tingling pain in the body part removed. One possible cause is that nerve fibers at the stump are stimulated and the brain interprets the signals as originating in the amputated portion. The other is the rearrangement within the cortical areas so that area say for the hand now responds to signals from other parts of the body but still interprets them as coming for the amputated hand.

 

However, for patients undergoing lower-extremity amputation under epidural anesthesia, not one of the 11 patients who received lumbar epidural blockade with bupivacaine and morphine for 72 hours before operation developed PLS. For people who underwent general anesthesia without prior lumbar epidural blockade, 5 of 14 patients had PLS at 6 weeks and 3 continued to experience PLS at 1 year.

 

Woolf and Chong have noted that perfect preoperative, intraoperative, and postoperative treatment comprises of “NSAIDs to reduce the activation/centralization of nociceptors, local anesthetics to block sensory inflow, and centrally acting drugs such as opiates.” Decreasing perioperative pain with preemptive techniques enhances satisfaction, hastens discharge, spares opioid use, along with diminished constipation, sedation, nausea, and urinary retention, and may even stop the development of chronic pain. Anesthesiologists and surgeons should consider integrating these techniques in their everyday practices.

 

When pain occurs as a result of damage or injury in consequence of surgery, the spinal cord can attain a hyperexcitable state wherein excessive pain reactions occur that may persist for days, weeks or even years.

 

Why does localized injury resulting from trauma result in chronic, intractable pain in some patients? Tissue injury leads to a constellation of changes in spinal excitability, including elevated spontaneous firing, greater response amplitude and length, decreased threshold, enhanced discharge to repeated stimulation, and expanded receptive fields. The persistence of these changes, which are collectively termed central sensitization, appears to be fundamental to the prolonged enhancement of pain sensitivity which defines chronic pain. Numerous drugs and/or medications as well as local anesthetic neural blockade may limit the magnitude of the central nervous system (CNS) windup, as evidenced by diminished pain and diminished opioid consumption in the preemptive analgesic models.

 

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Dr. Alex Jimenez’s Insight

Chiropractic care is an alternate treatment option which utilizes spinal adjustments and manual manipulations to safely and effectively restore as well as maintain the proper alignment of the spine. Research studies have determined that spinal misalignments, or subluxations, can lead to chronic pain. Chiropractic care is commonly utilized for pain management, even if the symptoms are not associated to an injury and/or condition in the musculoskeletal and nervous system. By carefully re-aligning the spine, a chiropractor can help reduce stress and pressure from the structures surrounding the main component of out body’s foundation, ultimately providing pain relief.

 

Enteric Nervous System Function and Pain

 

When it comes to the diminished use of drugs and/or medications, including opioids, in order to prevent side-effects like gastrointestinal health issues, the proper function of the enteric nervous system may be at play.

 

The enteric nervous system (ENS) or intrinsic nervous system is one of the key branches of the autonomic nervous system (ANS) and consists of a mesh-like system of nerves which modulates the role of the gastrointestinal tract. It’s capable of acting independently of the sympathetic and parasympathetic nervous systems, even though it might be affected by them. The ENS can also be called the second brain.�It is derived from neural crest cells.

 

The enteric nervous system in humans is made up of some 500 million neurons, including the numerous types of Dogiel cells, approximately one two-hundredth of the amount of neurons in the brain. The enteric nervous system is inserted into the lining of the gastrointestinal system, beginning at the esophagus and extending down to the anus. Dogiel cells, also known as cells of Dogiel, refers to some kind of multipolar adrenal tissues within the prevertebral sympathetic ganglia.

 

Cells of Dogiel | El Paso, TX Chiropractor

 

The ENS is capable of autonomous functions, such as the coordination of reflexes; even though it receives considerable innervation in the autonomic nervous system, it does and can operate independently of the brain and the spinal cord.�The enteric nervous system has been described as the “second brain” for a number of reasons. The enteric nervous system may operate autonomously. It normally communicates with the central nervous system (CNS) via the parasympathetic, or via the vagus nerve, and the sympathetic, that is through the prevertebral ganglia, nervous systems. However, vertebrate studies reveal that when the vagus nerve is severed, the enteric nervous system continues to function.

 

In vertebrates, the enteric nervous system includes efferent neurons, afferent neurons, and interneurons, all of which make the enteric nervous system capable of carrying reflexes and acting as an integrating center in the absence of CNS input. The sensory neurons report on mechanical and chemical conditions. The enteric nervous system has the ability to change its response based on such factors as nutrient and bulk composition. In addition, ENS contains support cells that are much like astroglia of the brain and a diffusion barrier around the capillaries surrounding ganglia that’s like the blood-brain barrier of blood vessels.

 

The enteric nervous system (ENS) plays a pivotal role in inflammatory and nociceptive processes. Drugs and/or medications that interact with the ENS have recently raised considerable interest because of their capacity to regulate numerous aspects of the gut physiology and pathophysiology. In particular, experiments in animals have demonstrated that�proteinase-activated receptors (PARs) may be essential to neurogenic inflammation in the intestine. Moreover, PAR2 agonists seem to induce intestinal hypersensitivity and hyperalgesic states, suggesting a role for this receptor in visceral pain perception.

 

Furthermore, PARs, together with the proteinases that activate them, represent exciting new targets for therapeutic intervention on the ENS. The scope of our information is limited to chiropractic as well as to spinal injuries and conditions. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at 915-850-0900 .

 

Curated by Dr. Alex Jimenez

 

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Additional Topics: Sciatica

Sciatica is medically referred to as a collection of symptoms, rather than a single injury and/or condition. Symptoms of sciatic nerve pain, or sciatica, can vary in frequency and intensity, however, it is most commonly described as a sudden, sharp (knife-like) or electrical pain that radiates from the low back down the buttocks, hips, thighs and legs into the foot. Other symptoms of sciatica may include, tingling or burning sensations, numbness and weakness along the length of the sciatic nerve. Sciatica most frequently affects individuals between the ages of 30 and 50 years. It may often develop as a result of the degeneration of the spine due to age, however, the compression and irritation of the sciatic nerve caused by a bulging or herniated disc, among other spinal health issues, may also cause sciatic nerve pain.

 

 

 

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EXTRA IMPORTANT TOPIC: Chiropractor Sciatica Symptoms

 

 

MORE TOPICS: EXTRA EXTRA: El Paso Back Clinic | Back Pain Care & Treatments