The Relationship Among Pain, Sensory Loss, and Small Nerve Fibers in Diabetes
- 1 April 2006
- journal article
- Published by American Diabetes Association in Diabetes Care
- Vol. 29 (4), 883-887
- https://doi.org/10.2337/diacare.29.04.06.dc05-2180
Abstract
OBJECTIVE—Many individuals with diabetes experience neuropathic pain, often without objective signs of large-fiber neuropathy. We examined intraepidermal nerve fibers (IENFs) to evaluate the role of small nerve fibers in the genesis of neuropathic pain. RESEARCH DESIGN AND METHODS—Twenty-five diabetic subjects with neuropathic pain and 13 without were studied. The pain was present for at least 6 months for which no other cause could be found. Punch skin biopsies were obtained from the distal leg. IENFs were stained using antibody to protein gene product 9.5 and counted with confocal microscopy. Neuropathy was graded by vibration perception and cold detection thresholds and the Michigan Neuropathy Screening Instrument. RESULTS—In the total cohort, IENF density was significantly lower in those with pain compared with those without (3 [1–6] vs. 10 [3–19], respectively, P = 0.02). There were significant inverse correlations between IENF and severity of neuropathy, with the pain group having a flatter gradient than their pain-free counterparts (P < 0.02). The difference in IENF density was greatest in subjects with less objective evidence of neuropathy (P ≤ 0.01). CONCLUSIONS—More severe loss of IENF is associated with the presence of neuropathic pain only in those with little or no objective sign of neuropathy. Thus, loss of IENF cannot explain pain in all cases, suggesting that different mechanisms underpin the genesis of pain at various stages of neuropathy.Keywords
This publication has 25 references indexed in Scilit:
- Chronic painful peripheral neuropathy in an urban community: a controlled comparison of people with and without diabetesDiabetic Medicine, 2004
- Skin denervation in type 2 diabetes: correlations with diabetic duration and functional impairmentsBrain, 2004
- The time course of epidermal nerve fibre regeneration: studies in normal controls and in people with diabetes, with and without neuropathyBrain, 2004
- Diagnosis of CIDPNeurology, 2002
- Sensory nerves in skinNeurology, 1999
- Small‐fiber sensory neuropathies: Clinical course and neuropathology of idiopathic casesAnnals of Neurology, 1998
- Cutaneous innervation in sensory neuropathiesNeurology, 1995
- Quantitative measurement of cutaneous perception in diabetic neuropathyMuscle & Nerve, 1995
- The epidemiology of diabetic neuropathyJournal of Diabetes and its Complications, 1992
- Acute and remitting painful diabetic polyneuropathy: a comparison of peripheral nerve fibre pathologyPain, 1992