NeuropathyAnswers.org

Neuropathy Glossary

Plain-language definitions of terms you'll encounter when researching peripheral neuropathy — written from primary medical literature.

Educational reference content — Editorial Standards

Reviewed and updated May 12, 2026

Peripheral neuropathy

Peripheral neuropathy is damage or dysfunction of the peripheral nerves — the network of nerves that connects the brain and spinal cord to the rest of the body, including the limbs, skin, internal organs, and muscles. The peripheral nerves carry sensory information from the body to the brain (sensations of touch, temperature, pain, position) and motor commands from the brain to the muscles. When these nerves are damaged, the result can include numbness, tingling, burning pain, muscle weakness, balance problems, and autonomic symptoms affecting organs like the heart, digestive tract, and bladder.1

Peripheral neuropathy is not a single disease but a category of conditions with many possible causes. Common causes include diabetes (the most frequent cause in developed countries), chemotherapy treatment, autoimmune diseases, vitamin deficiencies or toxicities, infections (including HIV and shingles), inherited disorders, alcohol-related nerve damage, and exposure to certain toxins. In roughly a third of patients, no cause is identified despite thorough investigation — this is termed idiopathic neuropathy.2

The pattern of nerve involvement varies. The most common pattern is distal symmetric polyneuropathy, in which symptoms begin in the longest nerves first (the feet) and progress upward. Other patterns include mononeuropathy (one nerve affected, such as carpal tunnel syndrome), multiple mononeuropathies (several nerves affected in separate locations), and autonomic neuropathy (affecting the nerves controlling automatic body functions).

The National Institute of Neurological Disorders and Stroke (NINDS) estimates that peripheral neuropathy affects approximately 20 million people in the United States, though the true number is likely higher because milder cases often go undiagnosed.

Footnotes

  1. National Institute of Neurological Disorders and Stroke (NINDS). Peripheral Neuropathy Information Page. https://www.ninds.nih.gov/health-information/disorders/peripheral-neuropathy ↩

  2. Hanewinckel R, van Oijen M, Ikram MA, van Doorn PA. The epidemiology and risk factors of chronic polyneuropathy. Eur J Epidemiol. 2016;31(1):5-20. PMID: 26700499. DOI: 10.1007/s10654-015-0094-6. ↩

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Small-fiber neuropathy

Small-fiber neuropathy (SFN) is a type of peripheral neuropathy that selectively damages the smallest nerve fibers — the thin unmyelinated C fibers and thinly-myelinated A-delta fibers responsible for pain, temperature, itch, and autonomic functions. Standard nerve conduction studies and electromyography measure only the larger myelinated fibers, which means these tests do not detect small-fiber neuropathy. Patients with small-fiber neuropathy frequently have normal NCS/EMG results despite having real and significant symptoms.1

Symptoms typically include burning, tingling, stabbing, or electric-shock sensations, most often beginning in the feet. Some patients experience these symptoms in a length-dependent pattern (starting in the feet and progressing upward), while others have a non-length-dependent pattern with patchy distribution including the face, scalp, or trunk. When autonomic small fibers are affected, additional symptoms may appear: changes in sweating, dizziness on standing, gastrointestinal symptoms, and bladder dysfunction.

Diagnosis is typically made by skin punch biopsy with measurement of intraepidermal nerve fiber density, which directly counts the small nerve fibers in a small piece of skin and compares the count to age-matched normal values.2 Other tests assessing small-fiber function include QSART (sudomotor testing), quantitative sensory testing, and corneal confocal microscopy.

Causes include diabetes and prediabetes, autoimmune diseases (particularly Sjögren's syndrome), vitamin B12 deficiency, vitamin B6 toxicity, post-viral conditions including long COVID, sodium channel gene mutations, and others. Roughly 30–50% of cases remain idiopathic after a thorough workup.

Footnotes

  1. Terkelsen AJ, Karlsson P, Lauria G, Freeman R, Finnerup NB, Jensen TS. The diagnostic challenge of small fibre neuropathy. Lancet Neurol. 2017;16(11):934-944. PMID: 29029847. DOI: 10.1016/S1474-4422(17)30329-0. ↩

  2. Lauria G, Hsieh ST, Johansson O, et al. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Eur J Neurol. 2010;17(7):903-912. PMID: 20642627. DOI: 10.1111/j.1468-1331.2010.03023.x. ↩

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Large-fiber neuropathy

Large-fiber neuropathy refers to peripheral neuropathy that primarily affects the large myelinated nerve fibers — the ones responsible for vibration sense, position sense (proprioception), light touch, and the motor signals that move muscles. Because these fibers conduct electrical signals quickly, they can be measured by standard nerve conduction studies and electromyography. Large-fiber damage shows up on these tests as slowed nerve conduction velocity, reduced signal amplitude, or both.1

Patients with large-fiber neuropathy typically experience numbness, loss of vibration sensation, difficulty with balance (particularly in the dark when visual feedback is absent), and in more advanced cases, muscle weakness. The classic finding on physical examination is loss of the ankle reflex and reduced vibration sensation at the great toe, both detected with bedside tools (a reflex hammer and a 128 Hz tuning fork).

Large-fiber neuropathy can occur alone or in combination with small-fiber neuropathy. Many of the most common causes of peripheral neuropathy — including diabetic peripheral neuropathy in its later stages, chronic inflammatory demyelinating polyneuropathy (CIDP), Charcot-Marie-Tooth disease, and chemotherapy-induced peripheral neuropathy from certain agents — affect both fiber types, though one may predominate.

The distinction between large-fiber and small-fiber neuropathy matters clinically because the diagnostic approach differs. Large-fiber neuropathy can be confirmed with NCS/EMG, while small-fiber neuropathy requires skin biopsy or other specialized testing.

Footnotes

  1. England JD, Gronseth GS, Franklin G, et al. Practice Parameter: evaluation of distal symmetric polyneuropathy: role of laboratory and genetic testing. Neurology. 2009;72(2):185-192. PMID: 19056666. DOI: 10.1212/01.wnl.0000336370.51010.a1. ↩

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Autonomic neuropathy

Autonomic neuropathy is damage to the autonomic nerves — the nerves that control automatic body functions including heart rate, blood pressure regulation, digestion, urination, sexual function, sweating, and pupil response. Autonomic neuropathy can occur alone or alongside the more familiar sensory and motor forms of peripheral neuropathy.1

The symptoms vary based on which autonomic functions are affected. Cardiovascular autonomic involvement can produce orthostatic hypotension (a drop in blood pressure when standing, causing lightheadedness or fainting), abnormal heart rate responses, and exercise intolerance. Gastrointestinal involvement can cause gastroparesis (delayed stomach emptying with nausea and early satiety), constipation, or diarrhea — sometimes alternating. Genitourinary involvement can produce bladder dysfunction (incomplete emptying, urgency, recurrent urinary tract infections) and sexual dysfunction. Sudomotor involvement affects sweating patterns, producing either reduced sweating or excessive sweating in some areas.

Diabetes is the most common cause of autonomic neuropathy in developed countries. Other causes include amyloidosis, autoimmune autonomic ganglionopathy, paraneoplastic syndromes (autonomic neuropathy associated with cancer), genetic disorders (such as hereditary amyloidosis and familial dysautonomia), and certain medications.

Diagnosis combines clinical assessment with autonomic function testing, which may include heart rate variability testing, tilt table testing, QSART (for sudomotor function), gastric emptying studies, and other specialized tests depending on which symptoms predominate.2

Footnotes

  1. Freeman R. Autonomic peripheral neuropathy. Lancet. 2005;365(9466):1259-1270. PMID: 15811460. DOI: 10.1016/S0140-6736(05)74815-7. ↩

  2. Spallone V, Ziegler D, Freeman R, et al. Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management. Diabetes Metab Res Rev. 2011;27(7):639-653. PMID: 21695768. DOI: 10.1002/dmrr.1239. ↩

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Mononeuropathy

Mononeuropathy is damage to a single peripheral nerve. This contrasts with polyneuropathy, in which many nerves throughout the body are affected. Mononeuropathy typically produces symptoms confined to the area supplied by the affected nerve.1

The most common mononeuropathy is carpal tunnel syndrome, which involves compression of the median nerve at the wrist. Symptoms include numbness, tingling, and sometimes pain in the thumb, index finger, middle finger, and the inner half of the ring finger, often worse at night. Other common mononeuropathies include ulnar neuropathy at the elbow (sometimes called cubital tunnel syndrome), peroneal neuropathy at the knee (which can produce foot drop), and Bell's palsy (a facial nerve mononeuropathy).

Mononeuropathies result from focal nerve injury, which may be caused by compression (the most common mechanism), trauma, infection (such as Lyme disease or herpes zoster), or vascular causes (when blood supply to a nerve is interrupted). They may also occur in the setting of systemic disease — diabetes, for example, increases the risk of mononeuropathy, particularly at common entrapment sites.

When multiple separate nerves are affected at different sites, the condition is called mononeuritis multiplex or multiple mononeuropathy. This pattern often suggests systemic causes such as vasculitis, requiring specific evaluation. Diagnosis of mononeuropathy typically involves clinical examination plus nerve conduction studies and electromyography to localize the lesion and assess severity.

Footnotes

  1. Stewart JD. Peripheral nerve fascicles: anatomy and clinical relevance. Muscle Nerve. 2003;28(5):525-541. PMID: 14571455. DOI: 10.1002/mus.10454. ↩

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Polyneuropathy

Polyneuropathy is a peripheral neuropathy that affects many nerves throughout the body, typically in a symmetric distribution. The most common pattern is distal symmetric polyneuropathy, in which the longest nerves are affected first — producing symptoms that begin in the feet and progress upward, eventually reaching the hands once leg involvement has progressed substantially.1

The length-dependent pattern reflects the metabolic vulnerability of long nerve fibers. Because these fibers must transport materials over greater distances and maintain greater membrane surface area, they are more susceptible to systemic factors that damage nerves. Common causes that produce length-dependent polyneuropathy include diabetes, chemotherapy, vitamin B12 deficiency, alcohol-related nerve damage, kidney failure, and hypothyroidism.

Some polyneuropathies follow non-length-dependent patterns, with symptoms appearing in patches across the body rather than starting in the feet. Non-length-dependent patterns more often suggest immune-mediated or inflammatory causes, including chronic inflammatory demyelinating polyneuropathy (CIDP), vasculitic neuropathy, and small-fiber neuropathy associated with Sjögren's syndrome.

Polyneuropathy can also be classified by which nerve fibers are predominantly affected: sensory (numbness, tingling, pain), motor (weakness), or autonomic (organ dysfunction), with many polyneuropathies affecting more than one category. Distal Symmetric Polyneuropathy is the formal term used in neurology for the most common pattern.2

Footnotes

  1. Callaghan BC, Price RS, Feldman EL. Distal Symmetric Polyneuropathy: A Review. JAMA. 2015;314(20):2172-2181. PMID: 26599185. DOI: 10.1001/jama.2015.13611. ↩

  2. England JD, Gronseth GS, Franklin G, et al. Distal symmetric polyneuropathy: a definition for clinical research. Neurology. 2005;64(2):199-207. PMID: 15668414. DOI: 10.1212/01.WNL.0000149522.32823.EA. ↩

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Diabetic peripheral neuropathy (DPN)

Diabetic peripheral neuropathy (DPN) is nerve damage caused by diabetes, most commonly producing a length-dependent pattern of numbness, tingling, burning pain, or loss of sensation that begins in the toes and progresses upward. It affects approximately 50% of people with diabetes over their lifetime, according to the American Diabetes Association.1

DPN develops through a combination of mechanisms related to chronic elevation of blood glucose. These include the accumulation of advanced glycation end-products, oxidative stress in nerve tissue, damage to the small blood vessels that supply nerves, and activation of inflammatory pathways. Both large and small nerve fibers are typically affected, though one may predominate at different stages.

The most common presentation is distal symmetric polyneuropathy with symptoms in both feet, often worse at night. Beyond the painful and uncomfortable symptoms, DPN also produces loss of protective sensation, which increases the risk of foot ulcers and infections that go unnoticed. Annual foot examinations are part of standard diabetes care for this reason.

A separate form, diabetic autonomic neuropathy, affects the nerves controlling internal organs and produces cardiovascular, gastrointestinal, urinary, and other symptoms. Focal diabetic neuropathies (such as diabetic amyotrophy and cranial mononeuropathies) are less common but recognized forms.

Diagnosis combines clinical examination (monofilament testing, vibration sense, reflexes), laboratory confirmation of diabetes, and exclusion of other potential causes of neuropathy. The Diabetes Control and Complications Trial established that intensive glycemic control reduces the development of clinical neuropathy in type 1 diabetes by approximately 60%.2

A separate page on this site provides a detailed patient overview of diabetic peripheral neuropathy.

Footnotes

  1. Pop-Busui R, Boulton AJM, Feldman EL, et al. Diabetic Neuropathy: A Position Statement by the American Diabetes Association. Diabetes Care. 2017;40(1):136-154. PMID: 27999003. DOI: 10.2337/dc16-2042. ↩

  2. Diabetes Control and Complications Trial (DCCT) Research Group. The effect of intensive diabetes therapy on the development and progression of neuropathy. Ann Intern Med. 1995;122(8):561-568. PMID: 7887548. ↩

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Chemotherapy-induced peripheral neuropathy (CIPN)

Chemotherapy-induced peripheral neuropathy (CIPN) is nerve damage caused by certain chemotherapy medications used to treat cancer. CIPN affects approximately 68% of patients within the first month after completing neurotoxic chemotherapy and persists in roughly 30% of patients beyond six months, according to a systematic review and meta-analysis published in Pain in 2014.1

The chemotherapy agents most associated with CIPN include the platinum compounds (cisplatin, oxaliplatin, carboplatin), the taxanes (paclitaxel, docetaxel), the vinca alkaloids (vincristine, vinblastine), bortezomib (used in multiple myeloma), thalidomide and lenalidomide, eribulin, and ixabepilone. Each agent produces a somewhat distinct pattern of neurotoxicity, though most CIPN involves predominantly sensory symptoms — numbness, tingling, burning, and pain — typically starting in the fingertips and toes.

Oxaliplatin produces a characteristic acute cold-induced neuropathy: within hours of infusion, patients experience cold-triggered tingling or pain in the hands, feet, jaw, and throat. This acute pattern is distinct from the cumulative chronic neuropathy that may develop with continued treatment. The coasting phenomenon — symptoms continuing to worsen for weeks or months after chemotherapy ends before stabilizing or improving — is a recognized feature of platinum-induced CIPN.2

CIPN recovery curves vary substantially by drug. Some agents produce predominantly reversible neuropathy; others produce persistent symptoms that may continue for years. The CIPN survivorship population — cancer survivors living with persistent post-treatment neuropathy — is increasingly recognized as an important clinical group with distinct unmet needs.

Footnotes

  1. Seretny M, Currie GL, Sena ES, et al. Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis. Pain. 2014;155(12):2461-2470. PMID: 25261162. DOI: 10.1016/j.pain.2014.09.020. ↩

  2. Pachman DR, Qin R, Seisler DK, et al. Clinical Course of Oxaliplatin-Induced Neuropathy: Results From the Randomized Phase III Trial N08CB. J Clin Oncol. 2015;33(30):3416-3422. PMID: 26282635. DOI: 10.1200/JCO.2014.58.8533. ↩

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Idiopathic neuropathy

Idiopathic neuropathy is peripheral neuropathy for which no specific cause has been identified despite an appropriate medical workup. Approximately 25–30% of patients evaluated for peripheral neuropathy receive this designation after standard testing fails to identify a contributing condition. The term "cryptogenic neuropathy" is sometimes used synonymously.1

The label does not mean the diagnosis is uncertain or that the medical evaluation was inadequate — it reflects current limits of medical knowledge. The American Academy of Neurology practice parameters establish what constitutes an appropriate workup for distal symmetric polyneuropathy, including assessment for diabetes (HbA1c and oral glucose tolerance testing), vitamin B12 deficiency, thyroid dysfunction, monoclonal gammopathy, and other reversible causes. When all standard testing returns normal, the neuropathy is labeled idiopathic.

A significant portion of patients initially labeled with idiopathic neuropathy are later found to have small-fiber neuropathy that was not initially recognized because skin punch biopsy was not performed. Recognition of small-fiber neuropathy in the idiopathic group, and identification of genetic causes (particularly sodium channel mutations) in some patients, has reduced the idiopathic category over time. Ongoing research continues to identify new causes.

Patients with idiopathic neuropathy can still benefit from the symptom management approaches developed for peripheral neuropathy generally, and the absence of an identified cause does not preclude effective management of symptoms.

Footnotes

  1. Wolfe GI, Baker NS, Amato AA, et al. Chronic cryptogenic sensory polyneuropathy: clinical and laboratory characteristics. Arch Neurol. 1999;56(5):540-547. PMID: 10328249. DOI: 10.1001/archneur.56.5.540. ↩

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Gabapentin

Gabapentin is a medication approved by the U.S. Food and Drug Administration for postherpetic neuralgia (the persistent nerve pain that follows shingles) and for use as adjunctive therapy in certain seizure disorders. It is commonly used off-label by physicians for other neuropathic pain conditions, including diabetic peripheral neuropathy and various forms of peripheral neuropathy. Gabapentin appears in the FDA-approved prescribing information for Neurontin (the original brand name) and in subsequent generic labels.1

The medication works by binding to a specific subunit of voltage-gated calcium channels in the nervous system, reducing the release of certain neurotransmitters involved in pain signaling. Despite its name and chemical structure resembling the neurotransmitter GABA, gabapentin does not directly act on GABA receptors.

Common side effects from FDA labeling include dizziness, drowsiness, fatigue, peripheral edema (swelling in the lower extremities), and weight gain. Older adults may be more susceptible to dizziness, balance problems, and confusion, which is relevant given that peripheral neuropathy disproportionately affects this age group. The medication should not be stopped abruptly because rebound symptoms can occur; physicians typically taper the dose gradually.

A Cochrane systematic review of gabapentin for chronic neuropathic pain in adults summarized the evidence base, including the number of patients who achieved meaningful pain reduction in placebo-controlled trials.2 The 2015 systematic review and meta-analysis by Finnerup and colleagues in Lancet Neurology placed gabapentin among the recommended pharmacological options for neuropathic pain based on the available evidence.3

Selection of any specific medication, dose, and treatment plan is a decision between the patient and their physician. This glossary entry is for educational reference and is not medication advice.

Footnotes

  1. U.S. Food and Drug Administration. Neurontin (gabapentin) prescribing information. NDA 020235. ↩

  2. Wiffen PJ, Derry S, Bell RF, et al. Gabapentin for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017;6(6):CD007938. PMID: 28597471. DOI: 10.1002/14651858.CD007938.pub4. ↩

  3. Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14(2):162-173. PMID: 25575710. DOI: 10.1016/S1474-4422(14)70251-0. ↩

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Pregabalin

Pregabalin is a medication approved by the U.S. Food and Drug Administration for several conditions including diabetic peripheral neuropathy, postherpetic neuralgia (nerve pain following shingles), fibromyalgia, neuropathic pain associated with spinal cord injury, and as adjunctive therapy for certain seizure disorders. It is sold under the brand name Lyrica and as a generic medication. Pregabalin is classified as a Schedule V controlled substance in the United States because of a recognized potential for misuse, though this risk is considered lower than for many other controlled substances.1

The medication works by binding to the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system, reducing the release of certain neurotransmitters involved in pain signaling. This mechanism is similar to that of gabapentin, though pregabalin is absorbed more predictably and reaches therapeutic levels more quickly.

Common side effects from FDA labeling include dizziness, drowsiness, dry mouth, peripheral edema (swelling in the lower extremities), blurred vision, weight gain, and difficulty concentrating. As with gabapentin, older adults may be more susceptible to balance problems and cognitive side effects, and abrupt discontinuation can produce withdrawal symptoms.

The 2015 systematic review and meta-analysis by Finnerup and colleagues in Lancet Neurology placed pregabalin among the recommended pharmacological options for neuropathic pain based on the available evidence.2 A Cochrane systematic review by Derry and colleagues evaluated pregabalin for neuropathic pain in adults.3

Selection of any specific medication, dose, and treatment plan is a decision between the patient and their physician. This glossary entry is for educational reference and is not medication advice.

Footnotes

  1. U.S. Food and Drug Administration. Lyrica (pregabalin) prescribing information. NDA 021446. ↩

  2. Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14(2):162-173. PMID: 25575710. DOI: 10.1016/S1474-4422(14)70251-0. ↩

  3. Derry S, Bell RF, Straube S, Wiffen PJ, Aldington D, Moore RA. Pregabalin for neuropathic pain in adults. Cochrane Database Syst Rev. 2019;1(1):CD007076. PMID: 30673120. DOI: 10.1002/14651858.CD007076.pub3. ↩

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Duloxetine

Duloxetine is a medication approved by the U.S. Food and Drug Administration for several conditions including diabetic peripheral neuropathic pain, fibromyalgia, chronic musculoskeletal pain, major depressive disorder, and generalized anxiety disorder. It is sold under the brand name Cymbalta and as a generic medication.1 Duloxetine is also recommended by the American Society of Clinical Oncology as a treatment option for chemotherapy-induced peripheral neuropathy, based on randomized trial evidence.2

Duloxetine is classified as a serotonin and norepinephrine reuptake inhibitor (SNRI). Its action in neuropathic pain is thought to involve increased availability of norepinephrine and serotonin in pathways that modulate pain signaling, separate from its antidepressant effects. Pain benefit may appear independent of any effect on mood.

Common side effects from FDA labeling include nausea (particularly during the first weeks of treatment), dry mouth, constipation, decreased appetite, fatigue, dizziness, increased sweating, and sleep changes. Liver enzyme elevations have been reported and the medication is generally avoided in patients with significant liver disease or heavy alcohol use. Abrupt discontinuation can produce withdrawal symptoms.

The 2015 Finnerup systematic review included duloxetine among the recommended pharmacological options for neuropathic pain.[^2] The Cochrane review by Lunn and colleagues evaluated duloxetine for the treatment of painful neuropathy and chronic pain.3

Selection of any specific medication, dose, and treatment plan is a decision between the patient and their physician. This glossary entry is for educational reference and is not medication advice.

Footnotes

  1. U.S. Food and Drug Administration. Cymbalta (duloxetine) prescribing information. NDA 021427. ↩

  2. Loprinzi CL, Lacchetti C, Bleeker J, et al. Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: ASCO Guideline Update. J Clin Oncol. 2020;38(28):3325-3348. PMID: 32663120. DOI: 10.1200/JCO.20.01399. ↩

  3. Lunn MPT, Hughes RAC, Wiffen PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database Syst Rev. 2014;(1):CD007115. PMID: 24385423. DOI: 10.1002/14651858.CD007115.pub3. ↩

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Amitriptyline

Amitriptyline is a tricyclic antidepressant medication approved by the U.S. Food and Drug Administration for the treatment of depression. It is used off-label by physicians for various chronic pain conditions including peripheral neuropathic pain, postherpetic neuralgia, and chronic tension-type headache, among others. The use of amitriptyline for nerve pain is supported by decades of clinical experience and a substantial body of research literature, though FDA labeling does not list peripheral neuropathy as an indication.1

The mechanism of action in neuropathic pain is complex and involves multiple pathways: inhibition of norepinephrine and serotonin reuptake, sodium channel blockade, and effects on other receptors. The pain-relieving effect typically appears at doses lower than those used to treat depression.

Common side effects from FDA labeling reflect the medication's broad receptor activity. These include sedation (which is why the medication is typically taken at bedtime), dry mouth, constipation, blurred vision, weight gain, orthostatic hypotension (a drop in blood pressure on standing), and urinary retention. Older adults are more susceptible to confusion, balance problems, and falls, particularly when amitriptyline is combined with other medications that affect the central nervous system. The American Geriatrics Society Beers Criteria identifies tricyclic antidepressants as medications to be used with caution in older adults.2

The 2015 Finnerup systematic review included tricyclic antidepressants among the recommended pharmacological options for neuropathic pain.[^2] A Cochrane review by Moore and colleagues evaluated amitriptyline for neuropathic pain in adults.3

Selection of any specific medication, dose, and treatment plan is a decision between the patient and their physician. This glossary entry is for educational reference and is not medication advice.

Footnotes

  1. National Library of Medicine. MedlinePlus. Amitriptyline. https://medlineplus.gov/druginfo/meds/a682388.html ↩

  2. 2023 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023;71(7):2052-2081. PMID: 37139824. DOI: 10.1111/jgs.18372. ↩

  3. Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ. Amitriptyline for neuropathic pain in adults. Cochrane Database Syst Rev. 2015;(7):CD008242. PMID: 26146793. DOI: 10.1002/14651858.CD008242.pub3. ↩

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Nerve conduction study (NCS)

A nerve conduction study (NCS) is an electrodiagnostic test that measures how quickly and how strongly electrical signals travel through the peripheral nerves. The test uses surface electrodes placed on the skin to deliver brief electrical stimuli and to record the responses. Patients typically describe the sensation as small electrical zaps — uncomfortable but tolerable. NCS measures the function of large myelinated nerve fibers and can identify abnormalities consistent with peripheral neuropathy, nerve compression syndromes (such as carpal tunnel syndrome), and other neuromuscular conditions.1

The test measures three main parameters: conduction velocity (how fast the signal travels), amplitude (how strong the signal is), and latency (how long it takes for the signal to reach the recording site). Slowing of conduction velocity typically suggests damage to the myelin sheath that insulates nerves; reduced amplitude typically suggests loss of nerve fibers. The pattern of abnormalities helps identify the type and distribution of nerve involvement.

NCS is typically performed by a neurologist or physiatrist with electrodiagnostic training, often in conjunction with electromyography (EMG). The combined NCS/EMG study takes 30 to 90 minutes depending on how many nerves are tested. A separate page on this site explains what to expect at an NCS/EMG appointment.

An important limitation: NCS measures only large myelinated fibers and does not detect small-fiber neuropathy. A normal NCS does not rule out neuropathy — it rules out large-fiber neuropathy. When small-fiber neuropathy is suspected, additional testing including skin punch biopsy is typically needed.2

Footnotes

  1. American Association of Neuromuscular & Electrodiagnostic Medicine. Patient information on nerve conduction studies. https://www.aanem.org/patients/nerve-conduction-studies ↩

  2. Tankisi H, Pugdahl K, Beniczky S, Andersen H, Fuglsang-Frederiksen A. Evidence-based recommendations for examination and diagnostic strategies of polyneuropathy electrodiagnosis. Clin Neurophysiol Pract. 2019;4:214-222. PMID: 31886447. DOI: 10.1016/j.cnp.2019.10.005. ↩

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Electromyography (EMG)

Electromyography (EMG) is an electrodiagnostic test that measures the electrical activity of muscles. A thin needle electrode is inserted into specific muscles, and the electrical signals produced by the muscle at rest and during voluntary contraction are recorded and analyzed. The test provides information about the function of motor nerves and the muscles they supply, and helps distinguish problems originating in nerves from problems originating in muscles.1

EMG is typically performed at the same visit as nerve conduction studies because the two tests provide complementary information. NCS evaluates nerve conduction directly; EMG evaluates the functional consequences in muscle and can identify denervation patterns that develop when nerves have been damaged for weeks or longer.

Patients typically describe the EMG needle as feeling like a brief pinch similar to a small injection. The needle is solid (not hollow like an injection needle) and does not inject any substance. The examiner moves the needle slightly to sample different areas of the muscle and listens to the electrical signals through a speaker. Each muscle examined takes a few minutes; the complete study examines a planned set of muscles based on the clinical question.

EMG can identify:

  • Denervation patterns from peripheral nerve damage
  • Radiculopathy (nerve root compression) at specific spinal levels
  • Myopathy (primary muscle disease) versus neurogenic disorders
  • Disorders of the neuromuscular junction
  • Patterns of motor neuron disease

The findings on EMG, combined with NCS, help neurologists and physiatrists characterize the type, location, and severity of nerve or muscle problems. The American Association of Neuromuscular and Electrodiagnostic Medicine provides patient information about electrodiagnostic studies.

Footnotes

  1. American Association of Neuromuscular & Electrodiagnostic Medicine. Patient information on electromyography (EMG). https://www.aanem.org/patients/needle-emg ↩

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Skin punch biopsy

A skin punch biopsy is a brief office procedure in which a small cylinder of skin is removed for laboratory analysis. In the context of peripheral neuropathy, skin punch biopsy is used to measure intraepidermal nerve fiber density (IENFD) — the count of small nerve fibers crossing into the upper layer of skin. Reduced IENFD compared to age-matched normative values is the currently accepted diagnostic test for small-fiber neuropathy.1

The procedure is straightforward. A 3-millimeter circular blade (the "punch") is used after local anesthesia to remove a sample from the lower leg, ankle, or thigh. Some protocols include samples from multiple sites to assess length-dependence. The procedure takes a few minutes per site, produces minimal discomfort, and leaves a small mark that typically heals without significant scarring. Stitches are usually not needed.

The biopsy is sent to a specialized laboratory that processes the tissue with immunohistochemistry to visualize the small nerve fibers and count them. Two laboratories most commonly receive these samples in the United States: Therapath in New York and the Corinthian Reference Lab. The European Federation of Neurological Societies and the Peripheral Nerve Society jointly published guidelines on the use of skin biopsy in the diagnosis of small fiber neuropathy.2

A reduction in IENFD below the lower limit of normal for the patient's age supports a diagnosis of small-fiber neuropathy. The test is generally well-tolerated and complications such as infection or significant bleeding are rare. Skin biopsy can also detect other types of small-fiber pathology including changes in nerve morphology that may help distinguish different underlying causes.

Footnotes

  1. Lauria G, Hsieh ST, Johansson O, et al. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Eur J Neurol. 2010;17(7):903-912. PMID: 20642627. DOI: 10.1111/j.1468-1331.2010.03023.x. ↩

  2. Devigili G, Tugnoli V, Penza P, et al. The diagnostic criteria for small fibre neuropathy: from symptoms to neuropathology. Brain. 2008;131(7):1912-1925. PMID: 18524793. DOI: 10.1093/brain/awn093. ↩

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QSART

QSART (Quantitative Sudomotor Axon Reflex Test) is a specialized test that measures the function of the small autonomic nerve fibers controlling sweating. The test evaluates one component of the autonomic nervous system and is used in the evaluation of small-fiber neuropathy and autonomic neuropathy.1

The procedure works by stimulating sweat production at specific skin sites and measuring the response. A mild electrical current is used to deliver a small dose of acetylcholine (a neurotransmitter) into the skin through a process called iontophoresis. The acetylcholine activates nearby sweat glands, and the sweat produced is collected in a special capsule on the skin surface where its volume is measured over time. The test is typically performed at four standard body sites: the forearm, the upper leg, the lower leg, and the foot.

The pattern and magnitude of the sweat responses help characterize the function of the autonomic small fibers. Reduced or absent responses at multiple sites can support a diagnosis of small-fiber neuropathy with autonomic involvement or of autonomic neuropathy as a primary process. A length-dependent pattern of reduction (worse at the foot, better at the forearm) is consistent with the typical pattern of peripheral neuropathy. A non-length-dependent pattern (patchy involvement without the expected gradient) may suggest different underlying causes.

QSART is typically performed in specialized autonomic function testing laboratories. The test takes approximately one hour. Patients are usually asked to avoid certain medications that affect autonomic function for a period before the test, including antihistamines, antidepressants, and decongestants. The test is generally well-tolerated; patients may feel mild warmth or tingling at the test sites.

Footnotes

  1. Low PA, Caskey PE, Tuck RR, Fealey RD, Dyck PJ. Quantitative sudomotor axon reflex test in normal and neuropathic subjects. Ann Neurol. 1983;14(5):573-580. PMID: 6651255. DOI: 10.1002/ana.410140513. ↩

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Peripheral nerve stimulator

A peripheral nerve stimulator (PNS) is a medical device that delivers electrical stimulation to a specific peripheral nerve to manage chronic pain. The device typically consists of a small electrode (the "lead") placed near the target nerve and a pulse generator that delivers electrical impulses according to programmed settings. Several different PNS devices have received FDA clearance through the 510(k) pathway for the treatment of chronic intractable pain of peripheral nerve origin.1

PNS devices fall into two broad categories based on implant duration. Percutaneous PNS systems are designed for short-term use, typically 60 days, with the lead remaining external to the body. Permanent implantable PNS systems involve a fully implanted lead and pulse generator intended for long-term use. The procedure to place either type is performed by a physician with appropriate training in interventional pain medicine, neurosurgery, or related specialties, typically in an outpatient setting.

The standard process involves a trial period in most cases. During the trial, a temporary lead is placed and the patient evaluates whether the stimulation provides meaningful pain reduction over a defined period (often seven days). If the trial is successful by predefined criteria, a permanent system may be implanted. The trial-then-permanent approach is intended to identify patients most likely to benefit from long-term therapy before committing to a permanent implant.

FDA-cleared indications for currently marketed PNS devices vary by product and typically specify "chronic intractable pain of peripheral nerve origin." Specific products are not endorsed or recommended on this site. Coverage by Medicare and commercial insurers varies and is governed by Local Coverage Determinations and individual payer policies. The 2014 Neuromodulation Appropriateness Consensus Committee published consensus guidelines on the appropriate use of peripheral nerve stimulation.2

Footnotes

  1. U.S. Food and Drug Administration. 510(k) Premarket Notification Database. Peripheral nerve stimulator devices. ↩

  2. Deer TR, Mekhail N, Provenzano D, et al. The appropriate use of neurostimulation of the spinal cord and peripheral nervous system for the treatment of chronic pain and ischemic diseases: the Neuromodulation Appropriateness Consensus Committee. Neuromodulation. 2014;17(6):515-550. PMID: 25112889. DOI: 10.1111/ner.12208. ↩

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Spinal cord stimulator

A spinal cord stimulator (SCS) is an implanted medical device that delivers electrical stimulation to the dorsal columns of the spinal cord to manage chronic pain. The device consists of one or more leads placed in the epidural space (a layer over the spinal cord) and a pulse generator implanted under the skin, typically in the lower back or buttock area. SCS has been used in clinical practice for decades and is FDA-approved (Premarket Approval, a higher regulatory standard than 510(k) clearance) for several chronic pain indications.1

In recent years, newer SCS systems using high-frequency (10 kHz) stimulation have received FDA approval for additional indications including painful diabetic neuropathy. The SENZA-PDN randomized trial evaluated 10 kHz spinal cord stimulation for painful diabetic neuropathy and was the basis for FDA approval of this indication for the Nevro Senza system.2 Other SCS systems use different waveforms including conventional tonic stimulation, burst stimulation, and high-density stimulation.

The implant procedure typically follows a two-step pattern. A trial period uses a temporary lead to evaluate whether stimulation provides meaningful pain reduction. If the trial is successful, a permanent system is implanted in a subsequent procedure. Both procedures are typically performed by interventional pain physicians or neurosurgeons in outpatient settings.

Adverse events from FDA labeling include risks associated with the implant procedure (infection, bleeding, lead migration), risks associated with hardware (device failure, the need for revision surgery), and stimulation-related effects (uncomfortable sensations, changes in stimulation pattern over time). MRI compatibility varies by device and patients with SCS systems should follow manufacturer-specific MRI conditional labeling.

Medicare coverage of SCS is governed by National Coverage Determination 160.7 and applicable Local Coverage Determinations, with coverage typically requiring a successful trial period and specific clinical criteria. Coverage of high-frequency SCS for painful diabetic neuropathy is an evolving area subject to current LCD specifications.

Footnotes

  1. U.S. Food and Drug Administration. Premarket Approval Database. Spinal cord stimulator systems. ↩

  2. Petersen EA, Stauss TG, Scowcroft JA, et al. Effect of High-frequency (10-kHz) Spinal Cord Stimulation in Patients With Painful Diabetic Neuropathy: A Randomized Clinical Trial. JAMA Neurol. 2021;78(6):687-698. PMID: 33818600. DOI: 10.1001/jamaneurol.2021.0538. ↩

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TENS unit

A TENS unit (Transcutaneous Electrical Nerve Stimulation) is an external device that delivers low-voltage electrical stimulation through electrodes placed on the skin. Unlike implantable nerve stimulators, TENS does not require a surgical procedure — the electrodes adhere to the skin and the small portable device delivers electrical impulses that the patient or clinician programs to specific intensity and frequency settings.1

TENS has been used in clinical practice for decades and is available without prescription (over-the-counter) in many countries including the United States, though clinical TENS units used in physical therapy or pain medicine settings typically offer more programming options than consumer units. Patients place the adhesive electrodes on the skin near the area of pain and adjust the settings to a level that produces a tingling or buzzing sensation without discomfort.

A Cochrane systematic review by Gibson and colleagues evaluated TENS for neuropathic pain in adults and described the available evidence for various neuropathic conditions.2 The review noted methodological limitations in the available trials.

TENS is generally considered safe when used as directed. Contraindications and cautions from device labeling include avoiding placement of electrodes on broken skin, over the eyes, on the front of the neck (carotid sinus area), or on patients with cardiac pacemakers or other implanted electronic devices without specific guidance. Some patients experience skin irritation under the electrodes.

TENS is sometimes used as part of a broader management plan for chronic neuropathic pain and may be tried before invasive options. Selection of TENS or any specific therapy is a decision between the patient and their physician, particularly when underlying conditions or implanted devices may affect safety.

Footnotes

  1. National Institute for Health and Care Excellence (NICE). Transcutaneous electrical nerve stimulation (TENS). Clinical knowledge summary. ↩

  2. Gibson W, Wand BM, O'Connell NE. Transcutaneous electrical nerve stimulation (TENS) for neuropathic pain in adults. Cochrane Database Syst Rev. 2017;9(9):CD011976. PMID: 28905362. DOI: 10.1002/14651858.CD011976.pub2. ↩

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