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 de velopment of peripheral inflammation. In this electrophysiological stu dy the ability of the nitric oxide synthase inhibitor 7-nitro indazole (7-NI), which does not block endothelial nitric oxide in vivo, to inh ibit the electrically evoked responses of dorsal horn neurones recorde d in both normal animals sind in animals 3 h after the injection of ca rrageenan into the ipsilateral hind paw, was investigated. In both nor mal and carrageenan inflamed animals, 7-NI (1-100 mu g), administered intrathecally, strongly inhibited the NMDA receptor mediated wind-up a nd post-discharge of the neurones, having relatively little effect on the acute C- or A beta-fibre evoked activity of the neurones. This inh ibitory action of 7-NI on the noxious evoked responses of the neurones was completely blocked by the prior intrathecal administration of 500 mu g of L-arginine. Inflammation did not alter the effects of 7-NI si nce there was no difference in the dose-response curve between the nor mal 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 g eneration of nitric oxide, which then participates in nociceptive tran smission. These effects appear to be independent of the vascular effec ts of NO. Inflammation-induced changes could facilitate activation of spinal NMDA receptors, such that nitric oxide is now generated by stim uli previously sub-threshold for this event. Previous studies, reporti ng a unique role of NO in nociceptive transmission following thr devel opment of peripheral inflammation, may have resulted from inadequate s timuli in the normal animal.