Effects of neonatal capsaicin treatment on nociceptive thresholds in the rat

The responsiveness to noxious thermal, mechanical, and chemical stimuli was examined in adult rats that had been treated neonatally with capsaicin. A range of capsaicin doses was employed to determine whether the neurotoxicity of capsaicin to primary afferent fibers would be manifested behaviorally in a selective effect on nociceptive thresholds to specific stimuli. Animals were given 5 to 100 mg/kg of capsaicin at 2 days of age and were examined 2 to 4 months later using the tail flick and hot plate tests to determine thermal thresholds, the paw pressure test to determine mechanical thresholds, and the formalin test to determine chemical thresholds. Significant impairments of treated animals' responses to all three types of stimuli were found at high doses of capsaicin and at doses which seem to lead to the depletion of only unmyelinated primary afferent fibers. Slightly higher doses of capsaicin were required to increase thermal nociceptive thresholds in the tail flick test as compared with the other tests, and mechanical nociception seemed to be the most sensitive to the effects of capsaicin. At any particular dose of capsaicin, considerable variability was found in the responsiveness of animals to noxious stimuli. This may partly explain the inconsistencies in studies of nociceptive thresholds in capsaicin-treated animals. The results also demonstrate the difficulty of correlating the degree of analgesia exhibited by these animals with the extent of loss of primary afferent fibers or with the depletion of afferent putative peptide transmitters.