Responses of C-fiber low threshold mechanoreceptors and nociceptors to cold were facilitated in rats persistently inflamed and hypersensitive to cold

Neurosci Res. 2003 Dec;47(4):409-19. doi: 10.1016/j.neures.2003.08.003.


Cold allodynia is an annoying symptom in conditions of chronic inflammation such as rheumatoid arthritis. To examine whether primary afferent nerve activities are changed in association with hypersensitivity to cold, we recorded single nerve activities from the sural nerve in persistently inflamed rats in vivo. Inflammation was induced by an injection of complete Freund's adjuvant (CFA) solution into the tibio-tarsal joint. Inflamed rats showed an increased number of paw shakes to paw immersion in 25 degrees C water (pre-inflammation: 1.15+/-0.58, 2-week inflammation: 4.70+/-1.15). We also recorded cutaneous C-fiber activities under pentobarbital anesthesia and studied their responses to thermal and mechanical stimuli. The response of C-low threshold mechanoreceptors to cooling (total discharges between 27 and 23 degrees C) increased 1.8-fold (control group: 5.17+/-1.04 impulses, inflamed group: 9.38+/-1.47 impulses). In addition, the proportion of C-nociceptor units responding to cold down to 2 degrees C was significantly greater in the inflamed group (9 out of 18 units; threshold: 10.0+/-2.6 degrees C) than in the intact group (1 out of 14 units; threshold: 4.0 degrees C). These results suggest that the facilitated responses of these primary afferents are associated with cold hypersensitivity in chronically inflamed conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Arthritis, Experimental / physiopathology*
  • Cold Temperature*
  • Freund's Adjuvant / toxicity
  • Male
  • Mechanoreceptors / physiology*
  • Nerve Fibers, Unmyelinated / physiology*
  • Neurons, Afferent / physiology
  • Nociceptors / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Sural Nerve / pathology
  • Sural Nerve / physiology


  • Freund's Adjuvant