Involvement of spinal neurokinin-1 receptors in the maintenance but not induction of carrageenan-induced thermal hyperalgesia in the rat.

The study was undertaken to assess the antihyperalgesic effect of L-732,138, (N-acetyl-L-tryptophan-3,5-bistrifluoromethyl benzyl ester), a non-peptide neurokinin-1 (NK1) receptor antagonist in rats when given intrathecally. The peripheral inflammation associated with behavioral hyperalgesia to a thermal stimulus was induced by intraplantar (i.pl.) injection of carrageenan. The thermal hyperalgesia was measured by paw withdrawal latency. Intrathecal (i.t.) injection of L-732,138 (100 nmol) at 3h after carrageenan markedly attenuated the paw withdrawal latency of the inflamed paw, but not that of the non-inflamed paw. L-732,138 (100 nmol, i.t.) given 10 min prior to carrageenan injection had no effect on the carrageenan-induced decrease in paw withdrawal latency to noxious thermal stimulus. The results demonstrate that NK1 receptor is involved in the maintenance but not the induction and development of thermal hyperalgesia evoked by carrageenan.