DEPRESSION OF C-FIBER-EVOKED ACTIVITY BY INTRATHECALLY ADMINISTERED REACTIVE RED-2 IN RAT THALAMIC NEURONS

To investigate the possible role of spinal purinoceptors in nociceptio n, the potent P-2-purinoceptor antagonist reactive red 2 was studied i n rats under urethane anesthesia in which nociceptive activity was eli cited by electrical stimulation of afferent C fibers in the sural nerv e and recorded from single neurons in the ventrobasal complex of the t halamus. Intrathecal (i.t.) application of reactive red 2 (6-200 mu g) caused a dose-dependent reduction of the evoked activity in thalamic neurons. The estimated ED50 was 30 mu g, and the maximum depression of nociceptive activity amounted to about 70% of the control activity at a dose of 100 mu g. Morphine, administered i.t. at a maximally effect ive dose (80 mu g), inhibited the evoked nociceptive activity by only up to 55% of the control activity. An i.t. co-injection of reactive re d 2 (100 mu g) and morphine (80 mu g) caused a maximum reduction of th e evoked thalamic activity by up to 85% of the control activity, thus, exceeding significantly the effect elicited by either drug alone. Sim ilarly, i.t. co-injection of almost equipotent dosages of reactive red 2 (30 mu g) and morphine (30 mu g) caused a maximum reduction of the evoked activity by up to 72% of the control activity, which again exce eded significantly the effect of either drug alone. The results sugges t that in rats reactive red 2 exerts antinociception by blockade of P- 2-purinoceptors in the spinal cord and, hence, support the idea that A TP may play an important role in spinal transmission of nociceptive si gnals. An activation of the spinal opioid system does not seem to cont ribute to the effect of reactive red 2 but might act additive or even synergistically with its antinociceptive action. (C) 1998 Elsevier Sci ence B.V. All rights reserved.