Capsaicin desensitization to plasma extravasation evoked by antidromic C-fiber stimulation is not associated with antinociception in the rat

The relationship of capsaicin desensitization to the antinociception produced by acute capsaicin administration was studied in the rat. Cutaneous application of 1 % capsaicin (3 × /day) for 1 day antagonized plasma extravasation evoked by either 5 % capsaicin applied to the dorsal surface of the hindpaw or antidromic stimulation of the saphenous nerve. Treatment with either 1 % or 5 % capsaicin (3 ×/day) for up to 4 days failed, however, to produce thermal antinociception as measured by the rat paw-withdrawal procedure. In contrast, intracutaneous injection of 100 μg capsaicin produced marked increases in paw-withdrawal response latencies for up to six hours after injection. These data demonstrate a dissociation between block of cutaneous plasma extravasation and thermal antinociception in the rat. The data provide in vivo evidence that desensitization of peripheral nociceptors by capsaicin cannot account for the antinociception observed following acute capsaicin administration. Finally, these data support the notion that some pharmacologic actions of capsaicin in the rat can be dissociated from frank neurotoxicity on the basis of concentration or dose.