Spinal neurokin(3) receptors facilitate the nociceptive flexor reflex via a pathway involving nitric oxide

The present study examined the effects of intrathecal administration of neu rokinin(3) receptor agonists on the electrically-evoked nociceptive flexor reflex in decerebrate and spinalized adult rats. The reflex was evoked by s timulating the isolated sural nerve at an intensity that activates C fibers and was measured by recording the number of compound potentials in the ips ilateral hamstring muscles. Intrathecal senktide (1-30 nmol), a neurokinin3 receptor agonist, dose-dependently facilitated the reflex reaching a maxim um effect of 230% of the baseline reflex at 10 nmol. SR 142801 (60 nmol), a non-peptide neurokinin3 receptor antagonist, blocked facilitation of the r eflex induced by 10 nmol senktide, providing further support that the effec t of senktide is mediated by neurokinin3 receptors. The intrathecal adminis tration of senktide (10 nmol) did not alter the monosynaptic reflex elicite d by stimulating the L5 dorsal root at an intensity that was at the thresho ld for activating A fibers. This indicates that the senktide-induced facili tation of the nociceptive flexor reflex was not at the level of the motor n euron. Pretreatment with NG-nitro-L-arginine methyl ester (30 nmol), a nitr ic oxide synthase inhibitor, attenuated the effect of senktide, indicating that facilitation of the reflex by senktide is also mediated by the product ion of nitric oxide. Data from the present work have shown that spinal neur okinin3 receptors facilitate the nociceptive flexor reflex through a pathwa y that involves interneurons and the production of NO. Therefore, neurokini n3 receptors are likely to be involved in enhancing nociceptive neurotransm ission at the level of the spinal cord. (C) 1999 International Association for the Study of Pain. Published by Elsevier Science B.V.