• D R Linden and V S Seybold.
• Program in Neuroscience, University of Minnesota, Minneapolis 55455, USA.
• Pain. 1999 Mar 1; 80 (1-2): 309-17.

AbstractAlthough intrathecally administered senktide, an agonist at the neurokinin3 receptor, attenuates withdrawal responses to noxious stimuli in the restrained animal, senktide increases motor neuron activity in spinal cords of neonatal rats and facilitates the electrically-evoked nociceptive flexor reflex in the adult rat. The present study examined the effects of intrathecal administration of senktide on withdrawal responses to noxious thermal and mechanical stimuli in awake, unrestrained, adult rats. Intrathecal administration of senktide (10 nmol) in chronically catheterized rats did not alter 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. Thermal hyperalgesia peaked 20-26 min following drug injection and returned to normal within 30 min. SR 142801 (60 nmol), a non-peptide neurokinin3 receptor antagonist, inhibited the senktide-induced hyperalgesia, providing further support that the effect of senktide is mediated by neurokinin3 receptors. Pretreatment with N(G)-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 skin temperature in the hind paw. Intravenous hexamethonium, a ganglionic nicotinic receptor antagonist, similarly increased paw temperature without decreasing withdrawal latency to radiant heat. Thus, the increased skin temperature associated with intrathecal senktide was insufficient to account for the thermal hyperalgesia observed. Collectively, the present work demonstrates that NK3 receptors mediate thermal but not mechanical hyperalgesia through a pathway that involves the production of NO.

40 keywords...

hide…