Amplification of spinal nociceptive transmission depends on the generation of nitric oxide in normal and carrageenan rats.

It has been proposed that nitric oxide (NO) is involved in the spinal transmission of nociceptive information, particularly following the development of peripheral inflammation. In this electrophysiological study the ability of the nitric oxide synthase inhibitor 7-nitro indazole (7-NI), which does not block endothelial nitric oxide in vivo, to inhibit the electrically evoked responses of dorsal horn neurones recorded in both normal animals and in animals 3 h after the injection of carrageenan into the ipsilateral hind paw, was investigated. In both normal and carrageenan inflamed animals, 7-NI (1-100 micrograms), administered intrathecally, strongly inhibited the NMDA receptor mediated wind-up and post-discharge of the neurones, having relatively little effect on the acute C- or A beta-fibre evoked activity of the neurones. This inhibitory action of 7-NI on the noxious evoked responses of the neurones was completely blocked by the prior intrathecal administration of 500 micrograms of L-arginine. Inflammation did not alter the effects of 7-NI since there was no difference in the dose-response curve between the normal and carrageenan animals. In normal animals, stimuli of sufficient duration/intensity to enable the activation of NMDA receptors to occur, shown in this study by the occurrence of wind-up, also lead to the generation of nitric oxide, which then participates in nociceptive transmission. These effects appear to be independent of the vascular effects of NO. Inflammation-induced changes could facilitate activation of spinal NMDA receptors, such that nitric oxide is now generated by stimuli previously sub-threshold for this event. Previous studies, reporting a unique role of NO in nociceptive transmission following the development of peripheral inflammation, may have resulted from inadequate stimuli in the normal animal.