Spinal neurokin3 receptors facilitate the nociceptive flexor reflex via a pathway involving nitric oxide

The present study examined the effects of intrathecal administration of neurokinin3 receptor agonists on the electrically-evoked nociceptive flexor reflex in decerebrate and spinalized adult rats. The reflex was evoked by stimulating the isolated sural nerve at an intensity that activates C fibers and was measured by recording the number of compound potentials in the ipsilateral hamstring muscles. Intrathecal senktide (1-30 nmol), a neurokinin3 receptor agonist, dose-dependently facilitated the reflex reaching a maximum effect of 230% of the baseline reflex at 10 nmol. SR 142801 (60 nmol), a non-peptide neurokinin3 receptor antagonist, blocked facilitation of the reflex induced by 10 nmol senktide, providing further support that the effect of senktide is mediated by neurokinin3 receptors. The intrathecal administration of senktide (10 nmol) did not alter the monosynaptic reflex elicited by stimulating the L5 dorsal root at an intensity that was at the threshold for activating A fibers. This indicates that the senktide-induced facilitation of the nociceptive flexor reflex was not at the level of the motor neuron. Pretreatment with N(G)-nitro-L-arginine methyl ester (30 nmol), a nitric oxide synthase inhibitor, attenuated the effect of senktide, indicating that facilitation of the reflex by senktide is also mediated by the production of nitric oxide. Data from the present work have shown that spinal neurokinin3 receptors facilitate the nociceptive flexor reflex through a pathway that involves interneurons and the production of NO. Therefore, neurokinin3 receptors are likely to be involved in enhancing nociceptive neurotransmission at the level of the spinal cord.