INTRATHECAL METHYSERGIDE ANTAGONIZES THE ANTINOCICEPTION, BUT NOT THEHYPERALGESIA PRODUCED BY MICROINJECTION OF BACLOFEN IN THE VENTROMEDIAL MEDULLA OF THE RAT

Microinjection of baclofen, a gamma-aminobutyric acids (GABA(B)) recep tor agonist, in the nucleus raphe magnus (NRM) or nucleus reticularis gigantocellularis pars alpha (NGCp alpha) of the rat produces antinoci ception at doses of 0.1-1.0 ng and hyperalgesia at doses of 30-150 ng in the tail-flick test. The antinociception is proposed to result from disinhibition oi spinally-projecting neurons in this region that cont ain serotonin. The hyperalgesia is proposed to result either from inhi bition of these neurons or from disinhibition of a serotonergic pain f acilitatory pathway that also originates in this area of the ventromed ial medulla. To determine the involvement of bulbospinal serotonergic pathways in the biphasic effects of baclofen, rats were pretreated int rathecally with either 30 mu g of methysergide or saline. Ten minutes later, either saline, 0.5 ng or 150 ng of baclofen was microinjected i n the NRM and NGCp alpha, and alterations in nociceptive threshold wer e assessed by the tail-flick and hot-plate tests. Intrathecal pretreat ment with methysergide prevented the increase in tail-flick latency pr oduced by 0.5 ng of baclofen, but did not prevent the decrease in tail -flick latency produced by 150 ng of baclofen. Neither dose of baclofe n altered hot-plate latency and this lack of effect was unchanged by m ethysergide. These data support the idea that the antinociceptive effe ct of low doses of baclofen in the tail-flick test is mediated by disi nhibition of a bulbospinal serotonergic projection and release of sero tonin in the spinal cord. These data also suggest that the hyperalgesi a produced by high doses of baclofen does not result from disinhibitio n of a serotonergic pain facilitatory pathway, but rather from direct inhibition of tonically-active pain inhibitory neurons in the NRM and NGCp alpha. (C) 1998 Published by Elsevier Science Ireland Ltd.