Withdrawal responses to heat and mechanical stimuli applied to the plantar surface of the rat hindpaw were measured before and after an intraplantar injection of capsaicin. In separate groups of rats, capsaicin doses of 1, 10 and 30 μg, and the vehicle were given into the center of the plantar surface in a volume of 10 μl. Withdrawal latency evoked by radiant heat and the frequency of withdrawal evoked by mechanical stimuli (von Frey monofilaments) were obtained from both hindpaws before and after injection. Hyperalgesia to heat was defined as a decrease in withdrawal latency and mechanical hyperalgesia was indicated by an increase in withdrawal response frequency. Intraplantar injection of capsaicin evoked nocifensive behavior characterized by lifting and guarding the injected paw which typically lasted up to 3 min following injection. Capsaicin produced a decrease in withdrawal latency to heat and increased the frequency of withdrawal to mechanical stimuli in a dose-dependent manner. These effects were observed on the injected paw only. The duration of hyperalgesia produced by capsaicin was also dose-dependent. Withdrawal latencies to heat were decreased up to 45 min following capsaicin while withdrawal responses to mechanical stimuli remained elevated up to 4 h. The area of mechanical hyperalgesia included most of the plantar surface and extended approximately 9 mm proximal and distal to the injection. Injection of the vehicle did not significantly alter withdrawal responses to heat or mechanical stimuli. These studies demonstrate that intraplantar injection of capsaicin in rats produces hyperalgesia to heat and mechanical stimuli. This model should be useful for correlative behavioral, physiological and pharmacological studies of underlying mechanisms of capsaicin-evoked hyperalgesia.
Bibliographical noteFunding Information:
This work was supported by a grant from the Minnesota Medical Foundation and from the National Institutes of Health (NS31223) to D.A. Simone. H.D. Gilchrist was supported by a PHS pre-doctoral fellowship (DA05592). The authors thank Dr Glenn Geisler for critically reading an early version of the manuscript.