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Neuropathy
Classification and external resources
ICD-10 G56. - G63.,
G90.0, G99.0
ICD-9 337.0-337.1,
356-357, 377
eMedicine topic list

Neuropathy is usually short for peripheral neuropathy. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings G00-G99 - Diseases of the Nervous system (G00-G09 Inflammatory diseases of the Central nervous system ( Bacterial meningitis G00-G99 - Diseases of the Nervous system (G00-G09 Inflammatory diseases of the Central nervous system ( Bacterial meningitis G00-G99 - Diseases of the Nervous system (G00-G09 Inflammatory diseases of the Central nervous system ( Bacterial meningitis G00-G99 - Diseases of the Nervous system (G00-G09 Inflammatory diseases of the Central nervous system ( Bacterial meningitis The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors Peripheral neuropathy is the term for damage to Nerves of the Peripheral nervous system, which may be caused either by diseases of the Nerve or from the Peripheral neuropathy is defined as deranged function and structure of peripheral motor, sensory, and autonomic neurons, involving either the entire neuron or selected levels. [1]

Contents

Classification

The four cardinal patterns of peripheral neuropathy are polyneuropathy, mononeuropathy, mononeuritis multiplex and autonomic neuropathy. Polyneuropathy is a Neurological disorder that occurs when many Peripheral nerves throughout the body malfunction simultaneously Mononeuropathy (or "mono Neuritis " is a type of Neuropathy that only affects a single Nerve. Mononeuritis multiplex is the clinical picture that arises from problems with multiple individual nerves serially or almost simultaneously Autonomic Neuropathy (also called visceral neuropathy) is a disease of the non-voluntary non-sensory Nervous system (i The most common form is (symmetrical) peripheral polyneuropathy, which mainly affects the feet and legs. The foot is an Anatomical structure found in many Animals It is the terminal portion of a limb which bears weight and allows Locomotion. In common usage the human leg is the lower limb of the Body, extending from the Hip to the Ankle, and including the Thigh, the

A radiculopathy involves spinal nerve roots, but if peripheral nerves are also involved the term radiculoneuropathy is used. Radiculopathy is not a specific condition but rather a description of a problem in which one or more nerves are affected and do not work properly (a Neuropathy)

The form of neuropathy may be further broken down by cause, or the size of predominant fiber involvement, i. e. large fiber or small fiber peripheral neuropathy. Small fiber peripheral neuropathy is a type of Neuropathy. It is also called small fiber neuropathy small fiber sensory neuropathy (SFSN and C fiber neuropathy Frequently the cause of a neuropathy cannot be identified and it is designated idiopathic. Idiopathic is an Adjective used primarily in Medicine meaning arising spontaneously or from an obscure or unknown cause.

Neuropathy may be associated with varying combinations of weakness, autonomic changes and sensory changes. Loss of muscle bulk or fasciculations, a particular fine twitching of muscle may be seen. Sensory symptoms encompass loss of sensation and "positive" phenomena including pain. This wikipedia entry will focus on the painful aspects of neurological conditions. Readers interested in a more detailed discussion of peripheral neuropathy should follow the links to the main entry. Peripheral neuropathy is the term for damage to Nerves of the Peripheral nervous system, which may be caused either by diseases of the Nerve or from the

Neuropathic pain

See also: Neuralgia

According to the most widely accepted definition, neuropathic pain is "initiated or caused by a primary lesion or dysfunction in the nervous system. Neuralgia is a painful disorder of the Nerves. Under the general heading of neuralgia are Trigeminal neuralgia (TN Atypical trigeminal neuralgia (ATN "[2] As much as 3% of the population is affected. [3]

Neuropathic pain may result from disorders of the peripheral nervous system or the central nervous system (brain and spinal cord). Thus, neuropathic pain may be divided into peripheral neuropathic pain, central neuropathic pain or mixed (peripheral and central) neuropathic pain.

Central neuropathic pain is found in spinal cord injury, multiple sclerosis, and some strokes. Fibromyalgia, a disorder of chronic widespread pain, is potentially a central pain disorder and is responsive to medications effective for neuropathic pain. [4]

Aside from diabetes (see Diabetic neuropathy) and other metabolic conditions, the common causes of painful peripheral neuropathies are herpes zoster infection, HIV-related neuropathies, nutritional deficiencies, toxins, remote manifestations of malignancies, genetic and immune mediated disorders. Diabetic neuropathies are neuropathic disorders that are associated with Diabetes mellitus. Herpes zoster (or simply zoster) commonly known as shingles, is a Viral disease characterized by a painful skin rash with Blisters in a limited [5][6]

Neuropathic pain is common in cancer as a direct result of cancer on peripheral nerves (e. Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled g. , compression by a tumor), as a side effect of some chemotherapy drugs, and as a result of radiation injury. Chemotherapy, in its most general sense refers to treatment of disease by chemicals that kill cells specifically those of micro-organisms or Cancer.

Symptoms

Neuropathy often results in numbness, abnormal sensations called dysesthesias and allodynias that occur either spontaneously or in reaction to external stimuli, and a characteristic form of pain, called neuropathic pain or neuralgia, that is qualitatively different from the ordinary nociceptive pain one might experience from stubbing a toe. Dysesthesia is defined as an unpleasant abnormal sensation It is caused by lesions of the nervous system peripheral or central and it involves abnormal sensations whether spontaneous Allodynia, meaning "other pain" is a Painful response to a usually non-painful stimulus and can be either static or mechanical Nociception (synonym nociperception is defined as "the neural processes of encoding and processing Noxious stimuli.

Neuropathic pain may have continuous and/or episodic (paroxysmal) components. The latter are likened to an electric shock. Common qualities of the pain include burning or coldness, "pins and needles" sensations, numbness and itching. "Ordinary" pain results from exclusive stimulation of pain fibers, while neuropathic pain often results from the firing of both pain and non-pain (touch, warm, cool) sensory nerve fibers serving the same area. The result is signals that the spinal cord and brain do not normally receive.

Treatments for neuropathic pain

Neuropathic pain can be very difficult to treat with only some 40-60% of patients achieving partial relief. [7]

Deciding on the best treatment for individual patients challenges both the art and science of medicine. Attempts to synthesize scientific studies into best practices are limited by such factors as differences in reference populations and a lack of head-to-head studies. Furthermore, there are few studies evaluating treatment combinations or the special needs of children.

It is common practice in medicine to designate classes of medication according to their most common or familiar use e. g. as "antidepressants" and "anti-epileptic drugs" (AED's). These drugs have alternate uses to treat pain because the human nervous system employs common mechanisms for different functions, for example ion channels for impulse generation and neurotransmitters for cell-to-cell signaling. Ion channels are pore-forming Proteins that help establish and control the small Voltage Gradient across the Plasma membrane of all living

In addition to the work of Dworkin, O'Connor and Backonja et al. , cited above, there have been several recent attempts to derive guidelines for pharmacological therapy. [8][9] These have combined evidence from randomized controlled trials with expert opinion. A randomized controlled trial (RCT is a type of scientific Experiment most commonly used in testing the Efficacy or Effectiveness of Healthcare

Favored treatments are certain antidepressants e. g tricyclics and selective serotonin-norepinephrine re-uptake inhibitors (SNRI's), anticonvulsants, especially pregabalin (Lyrica) and gabapentin (Neurontin), and topical lidocaine. Tricyclic antidepressants (abbreviation TCAs) are a class of Antidepressant drugs first used in the 1950s The anticonvulsants, also called antiepileptic drugs (abbreviated "AEDs" are a diverse group of pharmaceuticals used in the treatment of epileptic Pregabalin ( INN) (prɨˈgæbəlɨn is an Anticonvulsant drug used for Neuropathic pain and as an adjunct therapy for Partial seizures with or Gabapentin (brand name Neurontin) is a medication originally developed for the treatment of Epilepsy. Lidocaine ( INN) (ˈlaɪdoʊkeɪn or lignocaine (former BAN) (/ˈlɪgnoʊkeɪn/ is a common Local anesthetic and antiarrhythmic drug Opioid analgesics and tramadol are recognized as useful agents but are not recommended as first line treatments. An opioid is a chemical Substance that has a Morphine -like action in the body Tramadol ( INN) (ˈtræmədɒl is an atypical Opioid which is a centrally acting Analgesic, used for treating moderate to severe Pain.

Many of the pharmacologic treatments for chronic neuropathic pain decrease the sensitivity of nociceptive receptors, or desensitize C fibers such that they transmit fewer signals. Nociception (synonym nociperception is defined as "the neural processes of encoding and processing Noxious stimuli. Structure and Anatomy Location C fibers are found in the peripheral nerves of the somatic sensory system.

Antidepressants

Main article: Antidepressants

Antidepressants function differently in neuropathic pain than in depression. An antidepressant is a Psychiatric medication used for alleviating major depression or Dysthymia ('milder' depression Activation of descending norepinephrinergic and serotonergic pathways to the spinal cord limit pain signals ascending to the brain. Antidepressants will relieve neuropathic pain in non-depressed persons.

In animal models of neuropathic pain it has been found that compounds which only block serotonin reuptake do not improve neuropathic pain. [10][11][12][13][14][15][16][17] Similarly, compounds that only block norepinephrine reuptake also do not improve neuropathic pain. Norepinephrine ( INN) (abbreviated norepi or NE) or noradrenaline ( BAN) (abbreviated NA or NAd) is a Compounds such as duloxetine, venlafaxine, and milnacipran that block both serotonin reuptake and norepinephrine reuptake do improve neuropathic pain. Duloxetine (brand names Cymbalta, Yentreve) is a Serotonin-norepinephrine reuptake inhibitor (SNRI used for Major depressive disorder (MDD Venlafaxine (Effexor Efexor is an Antidepressant of the Serotonin-norepinephrine reuptake inhibitor (SNRI class first introduced by Wyeth in 1993 Milnacipran is an Antidepressant of the Serotonin-norepinephrine reuptake inhibitor class Serotonin (ˌsɛrəˈtoʊnən ( 5-hydroxytryptamine, or 5-HT) is a Monoamine Neurotransmitter synthesized in serotonergic Neurons

Tricyclic antidepressants may also work on sodium channels in peripheral nerves.

Anticonvulsants

Main article: Anticonvulsants

Pregabalin (Lyrica) and gabapentin (Neurontin) work by blocking specific calcium channels on neurons. The anticonvulsants, also called antiepileptic drugs (abbreviated "AEDs" are a diverse group of pharmaceuticals used in the treatment of epileptic Pregabalin ( INN) (prɨˈgæbəlɨn is an Anticonvulsant drug used for Neuropathic pain and as an adjunct therapy for Partial seizures with or Gabapentin (brand name Neurontin) is a medication originally developed for the treatment of Epilepsy. The actions of the anticonvulsants carbamazepine (Tegretol) and oxcarbazepine (Trileptal), especially effective on trigeminal neuralgia, are principally on sodium channels. Carbamazepine ("CBZ" is an Anticonvulsant and mood stabilizing drug used primarily in the treatment of Epilepsy and Bipolar disorder Oxcarbazepine (marketed as Trileptal by Novartis or Trexapin by Taro is an Anticonvulsant and mood stabilizing drug, used primarily Trigeminal neuralgia (TN, or Tic Doloureux, (also known as prosopalgia is a neuropathic disorder of the Trigeminal nerve that causes episodes of intense Sodium channels are Integral membrane proteins that form Ion channels, conducting sodium ions ( Na+) through a cell's Plasma membrane

Lamotrigine may have a special role in treating two conditions for which there are few alternatives, namely post stroke pain and HIV/AIDS-related neuropathy in that subgroup on antiretroviral therapy. [18]

Opioids

Main article: Opioids

Opioids, also known as narcotics, are increasingly recognized as important treatment options for chronic pain. An opioid is a chemical Substance that has a Morphine -like action in the body They are not considered first line treatments in neuropathic pain but remain the most consistently effective class of drugs for this condition. Opioids must be used only in appropriate individuals and under close medical supervision.

Several opioids, particularly methadone have NMDA antagonist activity in addition to their µ-opioid agonist properties. Methadone ( Dolophine Amidone Methadose Physeptone Heptadon and many others is a synthetic Opioid, used medically as an Analgesic, Antitussive

Methadone and ketobemidone possess NMDA antagonsism. Ketobemidone (Cliradon Ketogan Ketodur Cymidon Ketorax &c is a powerful Opioid Analgesic. Methadone does so because it is a racemic mixture; only the l-isomer is a potent µ-opioid agonist. In Chemistry, a racemic mixture, or racemate, is one that has equal amounts of left- and right-handed enantiomers of a chiral [19]

There is little evidence to indicate that one strong opioid is more effective than another. Expert opinion leans toward the use of methadone for neuropathic pain, in part because of NMDA antagonism. It is reasonable to base the choice of opioid on other factors. [20]

Topical agents

In some forms of neuropathy, especially post-herpes neuralgia, the topical application of local anesthetics such as lidocaine can provide relief. Lidocaine ( INN) (ˈlaɪdoʊkeɪn or lignocaine (former BAN) (/ˈlɪgnoʊkeɪn/ is a common Local anesthetic and antiarrhythmic drug A transdermal patch containing Lidocaine is available commercially in some countries.

Repeated topical applications of capsaicin, are followed by a prolonged period of reduced skin sensibility referred to as desensitization, or nociceptor inactivation. Capsaicin not only deplete substance P but also results in a reversible degeneration of epidermal nerve fibers. [21] Nevertheless, benefits appear to be modest. [22]

Marijuana and cannabinoids

Cannabinoids are modestly effective in reducing chronic pain. Cannabinoids ( are a group of terpeno[[phenol]]ic compounds present in Cannabis ( Cannabis sativa L Nabilone is a synthetic cannabinoid which is significantly more potent than delta-9-tetrahydrocannabinol (THC). Nabilone is a synthetic Cannabinoid with therapeutic use as an Antiemetic and as an adjunct Analgesic for Neuropathic pain. Nabilone produces less relief of chronic neuropathic pain and had more side effects than a weak opioid. [23]

The predominant adverse effects are CNS depression and cardiovascular effects which are mild and well tolerated but, psychoactive side effects limit their use. [24] A complicating issue may be a narrow therapeutic window; lower doses decrease pain but higher doses have the opposite effect. [25]

Sativex, a fixed dose combination of delta-9-tetrahydrocannabinol (THC) and cannabidiol, is sold as an oromucosal spray. It has some limited effect on multiple sclerosis pain. There are high rates of adverse effects (92%), especially dizziness and nausea and intoxication. About half the users will stop the drug after one year. [26]

Nabilone has some positive effects on the pain and other symptoms of fibromyalgia, at least in the short term. [27] Long-term studies are need to assess the probability of weight gain and other adverse effects.

A recent study showed smoked marijuana is beneficial in treating symptoms of HIV-associated peripheral neuropathy. Cannabis, also known as marijuana or marihuana, or ganja (from Hindi / Sanskrit: गांजा gānjā hemp) is a [28]

NMDA antagonism

The N-methyl-D-aspartate (NMDA) receptor seems to play a major role in neuropathic pain and in the development of opioid tolerance. The NMDA receptor ( NMDAR) is an Ionotropic receptor for Glutamate ( NMDA ( N -methyl D -aspartate is a name of its selective

Dextromethorphan is an NMDA antagonist at high doses. Dextromethorphan ( DXM or DM) is an Antitussive (cough suppressant drug found in many over-the-counter cold and Cough medicines

Experiments in both animals and humans have established that NMDA antagonists such as ketamine and dextromethorphan can alleviate neuropathic pain and reverse opioid tolerance. A receptor antagonist is a type of receptor ligand or Drug that does not provoke a biological response itself upon binding to a receptor, but blocks Ketamine is a drug for use in human and veterinary medicine developed by Parke-Davis (today a part of Pfizer) in 1962 Dextromethorphan ( DXM or DM) is an Antitussive (cough suppressant drug found in many over-the-counter cold and Cough medicines [29] Unfortunately, only a few NMDA antagonists are clinically available and their use is limited by unacceptable side effects.

Reducing sympathetic nervous stimulation

In some neuropathic pain syndromes, "crosstalk" occurs between descending sympathetic nerves and ascending sensory nerves. Increases in sympathetic nervous system activity result in an increase of pain; this is known as sympathetically-mediated pain.

Lesioning operations on the sympathetic branch of the autonomic nervous system are sometimes carried out. &trade The autonomic nervous system ( ANS) (or visceral nervous system) is the part of the Peripheral nervous system that acts as a Control

Dietary supplements

There are two dietary supplements that have clinical evidence showing them to be effective treatments of diabetic neuropathy; alpha lipoic acid and benfotiamine. [30]

A 2007 review of studies found that injected (parenteral) administration of alpha lipoic acid (ALA) was found to reduce the various symptoms of peripheral diabetic neuropathy. In Pharmacology and Toxicology, a route Lipoic acid is an Organic compound, one Enantiomer of which is an essential cofactor for many enzyme complexes [31] While some studies on orally administered ALA had suggested a reduction in both the positive symptoms of diabetic neuropathy (including stabbing and burning pain) as well as neuropathic deficits (paresthesia),[32] the metanalysis showed "more conflicting data whether it improves sensory symptoms or just neuropathic deficits alone". Paresthesia (pron /ˌpɛɹɪsˈθiʒə/ paraesthesia in British English, pron [31] There is some limited evidence that ALA is also helpful in some other non-diabetic neuropathies. [33]

Benfotiamine is a lipid soluble form of thiamine that has several placebo controlled double blind trials proving efficacy in treating neuropathy and various other diabetic comorbidities. Benfotiamine ( rINN, or S-benzoylthiamine O-monophoshate is a synthetic S-acyl derivative of Thiamine (vitamine B1 [34][35]

Other Modalities

In addition to pharmacological treatment several other modalities are commonly recommended. [36] While lacking adequate double blind trials, these have shown to reduce pain and improve patient quality of life for chronic neuropathic pain: chiropractic, massage, meditation, cognitive therapy,[37] and prescribed exercise. Chiropractic is a Health care profession that focuses on diagnosis treatment and prevention of mechanical disorders of the Musculoskeletal system, with special emphasis Meditation is a mental discipline by which one attempts to get beyond the conditioned "thinking" mind into a deeper state of relaxation or awareness Cognitive Therapy (CT is a type of Psychotherapy developed by American Psychiatrist Aaron T Some pain management specialists will try acupuncture, with variable results. History Antiquity In China, the practice of acupuncture can perhaps be traced as far back as

Transcutaneous electrical nerve stimulation (TENS) may be worth considering in chronic neurogenic pain. TENS, with certain electrical waveforms, appears to have an acupuncture-like function.

Infrared photo therapy has been used to treat neuropathic symptoms. [38] However, recent work has cast doubt on the value of this approach. [39]

Neuromodulators

Neuromodulation is a field of science, medicine and bioengineering that encompasses both implantable and non-implantable technologies (electrical and chemical) for treatment purposes. [40]

Implanted devices are expensive and carry the risk of complications. Available studies have focused on conditions having a different prevalence than neuropathic pain patients in general. More research is needed to define the range of conditions for which they might be beneficial.

Spinal Cord Stimulators And Implanted Spinal Pumps

Spinal cord stimulators, use electrodes placed adjacent to, but outside the spinal cord. The overall complication rate is one-third, most commonly due to lead migration or breakage. Lack of pain relief sometimes prompts device removal. [41]

Infusion pumps delivery medication directly to the fluid filled (subarachnoid) space surrounding the spinal cord. Opioids alone or opioids with adjunctive medication (either a local anesthetic or clonidine) or more recently ziconotide[42] are infused. Complications such as, serious infection (meningitis), urinary retention, hormonal disturbance and intrathecal granuloma formation have been noted.

There are no randomized studies of infusion pumps. For selected patients 50% or greater pain relief, is achieved in 38% to 56% at six months but declines with the passage of time. [43] These results must be viewed skeptically since placebo effects cannot be evaluated.

Motor Cortex Stimulation

Stimulation of the primary motor cortex through electrodes placed within the skull but outside the thick meningeal membrane (dura) has been used to treat pain. The level of stimulation is below that for motor stimulation. As compared with spinal stimulation, which requires a noticeable tingling (paresthesia) for benefit, the only palpable effect is pain relief. [44][45]

Deep Brain Stimulation

The best long-term results with deep brain stimulation have been reported with targets in the periventricular/periaqueductal grey matter (79%), or the periventricular/periaqueductal grey matter plus thalamus and/or internal capsule (87%). [46] There is a significant complication rate which increase over time. [47]

See also

References

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Neuropathy related organizations

External links


Dictionary

neuropathy

-noun

  1. (pathology) Any disease of the nervous system.
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