Common Terms & Glossary
A comprehensive glossary of medical terms, abbreviations, and concepts related to Small Fiber Neuropathy to help you better understand your condition and communicate effectively with healthcare providers.
A
Allodynia
Pain caused by stimuli that normally do not cause pain, such as light touch or clothing against the skin. Common in SFN patients, particularly affecting feet and hands.
Autonomic Neuropathy
Damage to nerves controlling involuntary body functions like heart rate, blood pressure, digestion, and temperature regulation. Often accompanies small fiber neuropathy in conditions affecting the ANS.
ANS
(Autonomic Nervous System)
The part of the nervous system controlling involuntary functions including heart rate, digestion, breathing, and blood pressure. Small fiber neuropathy can significantly impact ANS function.
A-delta Fibers
(Aδ)
ANA
(Antinuclear Antibodies)
Autoantibodies detected in blood that may indicate autoimmune processes. A positive ANA can support an immune-mediated cause of SFN.
Autoantibodies
Immune proteins that mistakenly target the body’s own tissues. Certain autoantibodies are investigated in suspected autoimmune small fiber neuropathy.
Autoimmune SFN
Subtype of small fiber neuropathy driven by immune dysregulation; may respond to immunotherapy such as IVIG or steroids.
Alpha-Lipoic Acid
(ALA)
Antioxidant supplement studied in diabetic neuropathy; some patients with SFN report reduced burning pain and improved nerve symptoms.
Amyloidosis
Protein deposition disorder that can cause SFN and autonomic neuropathy, including forms related to TTR mutations.
C
CIPN
(Chemotherapy-Induced Peripheral Neuropathy)
Nerve damage caused by certain chemotherapy drugs, often affecting small and large fibers. Can cause neuropathic pain, numbness, and tingling, particularly in hands and feet.
C-fibers
Unmyelinated small nerve fibers that transmit pain, temperature, and itch sensations. Primary target in small fiber neuropathy, leading to burning pain and temperature sensitivity.
CRPS
(Complex Regional Pain Syndrome)
Chronic pain condition with burning pain and autonomic changes that can overlap with small fiber dysfunction seen in SFN.
Cold Sensitivity
Exaggerated pain or discomfort triggered by cold exposure. Frequently reported by patients with small fiber neuropathy.
Corneal Confocal Microscopy
(CCM)
Noninvasive imaging technique that visualizes corneal small nerve fibers; can reflect systemic small fiber loss in SFN.
Comorbidity
A coexisting medical condition (e.g., diabetes, autoimmune disease) that can contribute to or worsen small fiber neuropathy.
Cytokines
Inflammatory signaling proteins. Dysregulated cytokines may mediate immune-related nerve injury and neuropathic pain in SFN.
D
Diabetic Neuropathy
Nerve damage caused by prolonged high blood sugar levels in diabetes. Often begins as small fiber neuropathy before progressing to affect larger nerve fibers. Most common cause of peripheral neuropathy.
Distal
Refers to areas farthest from the center of the body, typically hands and feet. SFN symptoms usually begin distally and progress proximally (toward the center).
DRG
(Dorsal Root Ganglion)
Nerve cell clusters near the spinal cord containing sensory neuron cell bodies. Important in neuropathic pain research and potential target for SFN treatments.
Dysautonomia
Dysfunction of the autonomic nervous system causing orthostatic intolerance, GI changes, and altered sweating, commonly reported with SFN.
Dysesthesia
Unpleasant abnormal sensations (burning, stinging, electric) characteristic of neuropathic pain in SFN.
Denervation
Loss of nerve supply; reduced epidermal innervation is seen on skin biopsy in SFN.
Differential Diagnosis
Systematic process to distinguish SFN from other causes of pain/numbness like large fiber neuropathy, radiculopathy, or entrapment.
E
EMG
(Electromyography)
Test measuring electrical activity in muscles and large nerve fibers. Often normal in pure small fiber neuropathy since it doesn't detect small fiber damage, requiring specialized tests like skin biopsy.
Erythromelalgia
Condition causing episodes of burning pain, warmth, and redness in hands and feet. Can be associated with small fiber neuropathy and mutations in sodium channels like Nav1.7.
Ehlers-Danlos Syndrome
(EDS)
Connective tissue disorder often associated with dysautonomia and sometimes small fiber neuropathy.
Etiology
The underlying cause of a condition. SFN has diverse etiologies including diabetes, autoimmune, genetic, toxic, and idiopathic.
I
IENFD
(Intraepidermal Nerve Fiber Density)
Measurement of small nerve fibers within the skin's epidermis obtained through skin biopsy. Gold standard diagnostic test for small fiber neuropathy, with reduced density indicating nerve damage.
Idiopathic
Of unknown cause. Approximately 40-60% of small fiber neuropathy cases are idiopathic, meaning no underlying condition can be identified despite thorough investigation.
IVIG
(Intravenous Immunoglobulin)
Treatment using pooled antibodies from donors, showing promise for immune-mediated small fiber neuropathy. Research suggests it may help improve nerve fiber density and reduce neuropathic pain.
Inflammation
Immune activation that can injure small fibers and contribute to neuropathic pain and autonomic dysfunction in SFN.
Immunotherapy
Immunomodulator
A therapy that adjusts immune responses, potentially reducing small fiber injury in immune-mediated SFN.
IgG Subclass
Subtypes of IgG antibodies sometimes measured when evaluating autoimmune causes of SFN.
G
Gabapentin
Anticonvulsant medication commonly used as first-line treatment for neuropathic pain in SFN. Works by reducing abnormal nerve firing and can help with burning pain, shooting sensations, and allodynia.
Genetic Testing
Glucose Intolerance
Prediabetes that can injure small fibers and precede diabetes. Early detection and glycemic control may prevent progression of SFN.
Gastrointestinal Dysmotility
Autonomic dysfunction of the gut leading to bloating, constipation, or diarrhea, often seen with SFN.
Glycemic Control
Managing blood glucose through diet, exercise, and medication to limit ongoing nerve injury in diabetic/prediabetic SFN.
L
LDN
(Low Dose Naltrexone)
Ultra-low dose (1.5-4.5mg) of naltrexone used off-label for neuropathic pain and autoimmune conditions. May help reduce inflammation and modulate immune system in some SFN patients, though research is still emerging.
Length-Dependent
Pattern where longest nerves are affected first, typically starting in toes and progressing upward. Most common pattern in small fiber neuropathy, following a "stocking-glove" distribution as nerve damage spreads proximally.
Large Fiber Neuropathy
Neuropathy affecting myelinated large fibers with vibration/proprioception loss and reduced reflexes; distinct from but may coexist with SFN.
Lidocaine Patch
Topical local anesthetic used to reduce localized neuropathic pain in SFN.
N
Nav1.7, Nav1.8, Nav1.9
Voltage-gated sodium channels found in C-fibers and pain-sensing neurons. Mutations or dysfunction in these channels can cause inherited neuropathic pain conditions. Targets for new pain medications.
NCS
(Nerve Conduction Study)
Test measuring speed and strength of electrical signals in large nerve fibers. Typically normal in pure small fiber neuropathy, as it cannot detect small fiber damage.
Neuropathic Pain
Pain caused by damage or dysfunction in the nervous system itself, rather than from tissue injury. Characterized by burning, shooting, or electric-like sensations. Hallmark of small fiber neuropathy.
Nociceptor
Specialized nerve endings that detect harmful stimuli and transmit pain signals. Small fiber neuropathy affects these receptors, leading to altered pain sensation and allodynia.
Non–Length-Dependent SFN
(NLD-SFN)
Pattern of SFN with patchy or proximal involvement (e.g., trunk, face) not following a stocking-glove distribution.
Nerve Growth Factor
(NGF)
Protein crucial for small fiber development and survival; dysregulation may contribute to pain signaling in SFN.
Neuropathy Disability Score
(NDS)
Clinical scale grading signs of neuropathy. Complements symptom measures to monitor severity and progression.
Neuropathy Symptom Score
(NSS)
Patient-reported questionnaire assessing symptoms of neuropathy, including burning, tingling, and pain severity.
P
Paresthesia
Abnormal sensations like tingling, "pins and needles," or numbness without external stimulation. Common early symptom in small fiber neuropathy, often affecting feet first.
Peripheral Neuropathy
General term for damage to nerves outside the brain and spinal cord. Small fiber neuropathy is a specific type affecting only the smallest nerve fibers.
PGP 9.5
(Protein Gene Product 9.5)
Protein marker used to stain nerve fibers in skin biopsies. Allows visualization and counting of intraepidermal nerve fiber density for SFN diagnosis.
POTS
(Postural Orthostatic Tachycardia Syndrome)
Condition causing rapid heart rate increase when standing, often associated with autonomic neuropathy. Can occur alongside small fiber neuropathy in some patients.
Pregabalin
Anticonvulsant medication similar to gabapentin but often more potent for neuropathic pain. FDA-approved for treating diabetic peripheral neuropathy and can be effective for burning pain and allodynia in SFN patients.
Pruritus
Chronic itch mediated by small sensory fibers; may accompany SFN even without visible skin changes.
Polyneuropathy
Diffuse involvement of many peripheral nerves. SFN represents a small-fiber predominant polyneuropathy.
Plasma Exchange
(PLEX)
Procedure that filters circulating autoantibodies; occasionally used for severe immune-mediated SFN.
Postherpetic Neuralgia
(PHN)
Persistent neuropathic pain after shingles; can mimic or coexist with SFN symptoms.
Q
QST
(Quantitative Sensory Testing)
Specialized testing measuring response to thermal and vibration stimuli. Can detect small fiber dysfunction by testing temperature sensation thresholds, complementing skin biopsy results.
QSART
(Quantitative Sudomotor Axon Reflex Test)
Test of sweat output assessing sudomotor function of small autonomic fibers, useful in evaluating autonomic neuropathy in SFN.
S
SFN
(Small Fiber Neuropathy)
Condition affecting the smallest nerve fibers responsible for pain, temperature sensation, and autonomic functions. Causes burning pain, temperature sensitivity, and potentially autonomic symptoms.
Skin Biopsy
3mm punch biopsy typically taken from leg to measure intraepidermal nerve fiber density. Gold standard diagnostic test for small fiber neuropathy, showing reduced nerve fiber count in affected patients.
Sudomotor
Relating to sweat gland function controlled by small autonomic nerve fibers. Sudomotor testing can detect autonomic neuropathy through evaluation of sweat response.
Stocking-Glove Distribution
Classic pattern of length-dependent SFN with symptoms starting in feet/hands and progressing proximally.
Sympathetic Nervous System
(SNS)
Branch of the autonomic nervous system involved in vasomotor control and sweating; dysfunction contributes to SFN symptoms.
T
Thermal Threshold Testing
Part of quantitative sensory testing measuring ability to detect warm and cool temperatures. Abnormal results suggest small fiber dysfunction, as these fibers transmit temperature sensation.
TTR
(Transthyretin)
Protein that can form amyloid deposits causing hereditary amyloidosis. TTR mutations can lead to progressive peripheral neuropathy including small fiber involvement.
V
VAS
(Visual Analog Scale)
0-10 pain rating scale used to measure neuropathic pain intensity. Standard tool in clinical trials and patient care for tracking pain severity in small fiber neuropathy.
Voltage-Gated Sodium Channels
Proteins in nerve cell membranes essential for electrical signal transmission. Dysfunction in channels like Nav1.7 can cause inherited pain disorders and are targets for new neuropathic pain treatments.