B. Driessen et al., DEPRESSION OF C-FIBER-EVOKED ACTIVITY BY INTRATHECALLY ADMINISTERED REACTIVE RED-2 IN RAT THALAMIC NEURONS, Brain research, 796(1-2), 1998, pp. 284-290
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.