GABAergic modulation of nociceptive threshold: effects of THIP and bicuculline microinjected in the ventral medulla of the rat

Neurons of the nucleus raphe magnus (NRM) and nucleus reticularis gigantocellularis pars alpha (NGCpα) have been implicated in the regulation of nociceptive threshold and production of antinociception. Previous studies have shown that the activity of these neurons is modulated by noradrenergic, cholinergic and serotonergic afferents. The present study examined whether these neurons are additionally subject to regulation by a GABAergic input. Microinjection of the GABA A receptor agonist 4 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP; 0.3 or 1.0 μg) in the NRM or NGCpα significantly decreased tail flick latency (TFL) and increased responsiveness to noxious pinch. Hot plate latency (HPL) was not affected by microinjection of 0.3 μg THIP. Although HPL was increased after microinjection of 1.0 μg THIP, this effect may reflect motoric disturbances. In contrast to the hyperalgesia produced by THIP, microinjection of the GABA A receptor antagonist bicuculline methiodide (0.04 or 0.1 μg) produced a small, but significant increase in TFL. Responsiveness to noxious pinch and HPL were not affected by either dose. These findings indicate that neurons of the NRM or NGCpα involved in the regulation of nociceptive threshold are subject to an inhibitory GABAergic input mediated by a GABA A receptor. However, in contrast to previously described inhibitory inputs, the GABAergic influence does not appear to be tonically active to a substantial extent in the unanesthetized rat.