Journal
NEUROSCIENCE
Volume 114, Issue 2, Pages 291-299Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0306-4522(02)00372-X
Keywords
diabetic neuropathy; resinoferatoxin; nociceptors; ectopic activity; myelinated afferents; hypersensitivity
Categories
Funding
- NIGMS NIH HHS [GM 64830] Funding Source: Medline
- NINDS NIH HHS [NS 41178] Funding Source: Medline
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM064830] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R21NS041178] Funding Source: NIH RePORTER
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Both myclinated and unmyclinated afferents are implicated in transmitting diabetic neuropathic pain. Although unmyclinated afferents are generally considered to play a significant role in diabetic neuropathic pain, pathological changes in diabetic neuropathy occur mostly in myclinated A-fibers. In the present study, we first examined the role of capsaicin-sensitive C-fibers in the development of allodynia induced by diabetic neuropathy. We then studied the functional changes of afferent nerves pertinent to diabetic neuropathic pain. Diabetes was induced in rats by i.p. streptozotocin. To deplete capsaicin-sensitive C-fibers, rats were treated with i.p. resiniferatoxin (300 mug/kg). Mechanical and thermal sensitivities were measured using von Frey filaments and a radiant heat stimulus. Sing-le-unit activity of afferents was recorded from the tibial nerve. Tactile allodynia, but not thermal hyperalgesia, developed in diabetic rats. Resiniferatoxin treatment did not alter significantly the degree and time course of allodynia. Post-treatment with resiniferatoxin also failed to attenuate allodynia in diabetic rats. The electrophysiological recordings revealed ectopic discharges and a higher spontaneous activity mainly in Adelta- and Abeta-fiber afferents in diabetic rats regardless of resiniferatoxin treatment. Furthermore, these afferent fibers had a lower threshold for activation and augmented responses to mechanical stimuli. Thus, our study suggests that capsaicin-sensitive C-fiber afferents are not required in the development of allodynia in this rat model of diabetes. Our electrophysiological data provide substantial new evidence that the abnormal sensory input from Adelta- and Abeta-fiber afferents may play an important role in diabetic neuropathic pain. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.
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