Role of primary afferent nerves in allodynia caused by diabetic neuropathy in rats

Neuroscience. 2002;114(2):291-9. doi: 10.1016/s0306-4522(02)00372-x.


Both myelinated and unmyelinated afferents are implicated in transmitting diabetic neuropathic pain. Although unmyelinated afferents are generally considered to play a significant role in diabetic neuropathic pain, pathological changes in diabetic neuropathy occur mostly in myelinated 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 microg/kg). Mechanical and thermal sensitivities were measured using von Frey filaments and a radiant heat stimulus. Single-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Afferent Pathways / drug effects
  • Afferent Pathways / pathology
  • Afferent Pathways / physiopathology*
  • Animals
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetic Neuropathies / pathology
  • Diabetic Neuropathies / physiopathology*
  • Disease Models, Animal
  • Diterpenes / pharmacology
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / pathology
  • Ganglia, Spinal / physiopathology*
  • Hyperalgesia / pathology
  • Hyperalgesia / physiopathology*
  • Male
  • Microscopy, Electron
  • Nerve Fibers, Myelinated / drug effects
  • Nerve Fibers, Myelinated / pathology
  • Nerve Fibers, Myelinated / physiology*
  • Nerve Fibers, Unmyelinated / drug effects
  • Nerve Fibers, Unmyelinated / pathology
  • Nerve Fibers, Unmyelinated / physiology*
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / pathology
  • Neurons, Afferent / physiology*
  • Nociceptors / drug effects
  • Nociceptors / physiopathology*
  • Pain Threshold / drug effects
  • Pain Threshold / physiology
  • Physical Stimulation
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Tibial Nerve / pathology
  • Tibial Nerve / physiology
  • Tibial Nerve / ultrastructure


  • Diterpenes
  • resiniferatoxin