DEPRESSION OF A-FIBER-EVOKED AND C-FIBER-EVOKED SEGMENTAL REFLEXES BYMORPHINE AND CLONIDINE IN THE IN-VITRO SPINAL-CORD OF THE NEONATAL RAT

1 Population synaptic responses of motoneurones were recorded from a v entral root following electrical stimulation of the corresponding lumb ar dorsal root in neonatal rat hemisected spinal cord preparations in vitro. Two levels of electrical stimulation were used to elicit dorsal root compound action potentials that contained either an A fibre comp onent alone or both A and C fibre components. The effects of centrally acting analgesics and an N-methyl-D-aspartate (NMDA) receptor antagon ist were tested on synaptic responses produced by these two levels of stimulation. 2 At stimulus intensities below four times threshold (T) there was no C fibre component in the dorsal root compound action pote ntial. Responses to a single pulse at 3T (the low intensity excitatory postsynaptic potential (e.p.s.p.)), a train of five pulses at 2T (the train e.p.s.p.) and a single supramaximal pulse (the high intensity e .p.s.p.) were used to compare the depressant actions of morphine, clon idine and the competitive NMDA antagonist CGP40116 (D-(E)-2-amino-4-me thyl-5-phosphono-pentenoic acid). The train e.p.s.p. (mean half-time t o decay 5+/-0.6 s, n=6) had a similar profile to the high intensity e. p.s.p. (mean half-time to decay 6.8+/-0.7, n=8). 3 The monosynaptic co mpound action potential of motoneurones (MSR) was resistant to all thr ee drugs irrespective of the intensity of dorsal root stimulation. The low intensity e.p.s.p., the train e.p.s.p. and the high intensity e.p .s.p. were depressed by all three drugs. The EC(50) values for depress ion by morphine were 79+/-1 nM (n=8) for the high intensity e.p.s.p. a nd 99+/-1 nM (n=4) for the low intensity e.p.s.p. The corresponding va lues for clonidine were 25+/-1 nM (n=8) and 9+/-1 nM (n=4) and those f or CGP40116 were 860+/-1.3 nM (n=4) and 76+/-1.1 nM (n=4). 4 The depre ssant profile of the NMDA antagonist, having the least depressant acti vity on the C fibre-mediated response, was different from that of the two analgesics. CGP40116 (3 mu M) depressed the high intensity e.p.s.p . to 62+/-8%, the low intensity e.p.s.p. to 22+/-4% and the train e.p. s.p. to 16+/-2% of control values. 5 The depressant actions of morphin e were fully reversed by naloxone (1 mu M) and those of clonidine were fully reversed by atipamezole (1 mu M). 6 These results show that, in contrast to previous findings, activation of primary afferent C fibre s in dorsal roots is not required for generation of morphine- or cloni dine-sensitive synaptic responses in ventral roots of this in vitro pr eparation.