Modulation of carbachol-induced antinociception from the rat periaqueductal gray.

The tail-flick latency (TFL) and the vocalisation test (VT) thresholds were all increased by microinjecting CCh into the dorsal periaqueductal gray (dPAG) of rats. The effects on the TFL were mimicked by dimethyl-phenylpiperazinium, and inhibited by local mecamylamine or intraperitoneal (i.p.) phenoxybenzamine. The effects on the VT were mimicked by bethanechol and inhibited by local mecamylamine, atropine or naloxone. The effects on the thresholds for motor defence reaction were inhibited by i.p. methysergide or naloxone, and prolonged by i.p. phenoxybenzamine. The effects on the threshold for vocalisation during the stimulation were blocked by i. p. methysergide and shortened by i.p. phenoxybenzamine or naloxone. No significant effect of CCh was found on open arm exploration of rats in the elevated plus maze paradigm. We conclude that the effects of CCh from the dPAG is not due to an anxiolytic effect, and depends on the activation of local cholinergic and opioid sites for the supraspinal modulation of "affective" component of pain response, and nicotinic sites for the activation of descending pain pathways.