Antinociception induced by local injections of carbachol into the nucleus raphe magnus in rats: alteration by intrathecal injection of monoaminergic antagonists.

Electrical stimulation of neurons located in the nucleus raphe magnus (NRM) produces antinociception which appears to result from inhibition of spinothalamic tract neurons located in the spinal cord dorsal horn. Iontophoretic application of acetylcholine also activates NRM neurons and microinjection of cholinergic agonists such as carbachol into the NRM produces a profound, long-lasting antinociception. Since the antinociception induced by electrical stimulation of NRM neurons is mediated, at least in part, by bulbospinal serotonergic and noradrenergic neurons, the role of these monoaminergic neurons in mediating the antinociception induced by microinjecting carbachol in the NRM was examined in the present study. To this end, various antagonists of serotonin and norepinephrine were injected into the spinal cord subarachnoid space following the induction of antinociception by the local injection of carbachol into the NRM. The serotonergic antagonist methysergide had no effect on carbachol-induced antinociception. However, the alpha 2-noradrenergic antagonist yohimbine attenuated, while the alpha 1-noradrenergic antagonists prazosin and WB4101 increased the effects of carbachol. The non-selective noradrenergic antagonist phentolamine also attenuated the effects of carbachol. These results lead to the suggestion that the antinociception induced by the local injection of carbachol into the NRM is mediated by selective activation of bulbospinal noradrenergic neurons. Furthermore, the antinociception resulting from the activation of these descending noradrenergic neurons appears to be mediated by alpha 2-noradrenergic receptors located in the spinal cord dorsal horn. Finally, the local injection of carbachol into the NRM also appears to activate another population of noradrenergic neurons which produces hyperalgesia mediated by alpha 1-noradrenergic receptors.