Spinal neurokinin(3) receptors mediate thermal but not mechanical hyperalgesia via nitric oxide

Although intrathecally administered senktide, an agonist at the neurokinin( 3) receptor, attenuates withdrawal responses to noxious stimuli in the rest rained animal, senktide increases motor neuron activity in spinal cords of neonatal rats and facilitates the electrically-evoked nociceptive flexor re flex in the adult rat. The present study examined the effects of intratheca l administration of senktide on withdrawal responses ro noxious thermal and mechanical stimuli in awake, unrestrained, adult rats. Intrathecal adminis tration of senktide (10 nmol) in chronically catheterized rats did not alte r the responses elicited by a noxious mechanical stimulus (508 mN, von Frey monofilament). Conversely, intrathecal senktide (10 nmol) induced thermal hyperalgesia, indicated by decreased withdrawal latency to radiant heat. Th ermal hyperalgesia peaked 20-26 min following drug injection and returned t o normal within 30 min. SR 142801 (60 nmol), a nonpeptide neurokinin(3) rec eptor antagonist, inhibited the senktide-induced hyperalgesia, providing fu rther support that the effect of senktide is mediated by neurokinin3 recept ors. Pretreatment with NG-nitro-L-arginine methyl ester (30 nmol), a nitric oxide synthase inhibitor, blocked the effect of senktide, indicating that senktide-induced thermal hyperalgesia is also mediated by the production of nitric oxide. Intrathecal senktide produced vasodilation and increased ski n temperature in the hind paw. Intravenous hexamethonium, a ganglionic nico tinic receptor antagonist, similarly increased paw temperature without decr easing withdrawal latency to radiant heat. Thus, the increased skin tempera ture associated with intrathecal senktide was insufficient to account for t he thermal hyperalgesia observed. Collectively, the present work demonstrat es that NK3 receptors mediate thermal but not mechanical hyperalgesia throu gh a pathway that involves the production of NO. (C) 1999 International Ass ociation for the Study of Pain. Published by Elsevier Science B.V.