Hypoalgesia following microinjection of noradrenergic antagonists in the nucleus raphe magnus.

The influence of the noradrenergic input to the nucleus raphe magnus (NRM) on the capacity of this nucleus to modulate nociceptive threshold was investigated in rat by microinjection of noradrenergic (NA) antagonists in the NRM. The distribution of NA terminals associated with the NRM was visualized histochemically using a glyoxylic acid-induced fluorescence technique. Microinjection of 5.0 and 10.0 micrograms phentolamine at sites within the NRM, which was found to be densely innervated by NA terminals, produced a dose-related hypoalgesia as assessed by both the tail flick and hot plate tests. Microinjection of these doses at sites close to yet outside the NRM, in areas less densely innervated with NA terminals, was either ineffective or produced hypoalgesia only after a substantial delay. Similar results were obtained following microinjection of 10.5 micrograms azapetine, another NA antagonist. The correspondence between the distribution of NA terminals associated with the NRM and the distribution of active sites for hypoalgesia in this area suggests that hypoalgesia was caused by blockade of the NA input to the NRM. These results indicate that those cells of the NRM involved in the modulation of nociceptive threshold are themselves subject to a tonic, inhibitory NA input, the suppression of which produces hypoalgesia.