Abstract

Focal electrical stimulation and glutamate microinjection in the nuclei reticularis gigantocellularis (NGC) and gigantocellularis pars alpha (NGC alpha) both inhibit the nociceptive tail-flick (TF) reflex in rats. The present experiments were undertaken to determine the transmitter(s) at the level of the lumbar spinal cord mediating descending inhibition of the TF reflex produced by activation of the NGC/NGC alpha. Intrathecal administration of atropine (7.2-57.6 nmol) produced a dose-dependent increase in the electrical stimulation threshold required for inhibition of the TF reflex. Phentolamine (47.2 or 94.4 nmol) and methysergide (32 or 64 nmol) also increased the stimulation threshold significantly, but only at the greater doses. Neither naloxone (27.5 or 55 nmol) nor mecamylamine (49.1 or 98.2 nmol) affected stimulation thresholds for inhibition of the TF reflex. Stimulation at threshold intensities for inhibition did not change the blood pressure significantly at most sites of stimulation in the NGC/NGC alpha (25/39). Intrathecal administration of atropine, phentolamine or methysergide did not affect resting blood pressure or changes associated with stimulation in most cases, although inhibition of the TF reflex by stimulation in the NGC/NGC alpha was affected consistently by these pretreatments. Similarly, glutamate (100 nmol, 0.5 microliter/1.5 min) microinjection produced a short-lasting inhibition (4.63 +/- 0.70 min, n = 19) of the TF reflex. Glutamate microinjection produced both pressor and depressor effects which were not affected by intrathecal pretreatment. Inhibition of the TF reflex by glutamate was attenuated significantly by intrathecal pretreatment with atropine, scopolamine, phentolamine and methysergide, but not naloxone or mecamylamine. These findings suggest that either a descending or local spinal cholinergic system, together with descending serotonergic and noradrenergic systems, are involved in the centrifugal inhibition of spinal nociceptive transmission from the NGC/NGC alpha.