Functional changes in the descending antinociceptive system of morphine-dependent rats

Functional changes of the descending antinociceptive system were studied in morphine-dependent rats by two types of experiments: (a) by recording the effects produced on nociceptive responses of the somesthetic thalamus by stimulation of the nucleus raphe magnus (NRM), and (b) by analyzing changes in the tonic activity of neurons in the periaqueductal gray matter (PAG). Poststimulus time histograms indicated that the input of A-alpha, A-delta, and C fibers into the spinal cord was conveyed via the spinothalamic tract (STT) to particular neurons of the nucleus ventralis posterolateralis (nVPL). Spikes of their responses were grouped in a short-latency burst followed by late spikes that occurred at the appropriate intervals for the arrival of the excitations originally initiated in the A-delta and C fibers. Only the histograms with late peaks were evaluated for the influence of the antinociceptive system. Stimulation of the NRM prior to stimulation of the sciatic nerve promptly suppressed the late A-delta and C-fiber) peaks in morphine-naive animals. In morphine-dependent rats, NRM stimulation had little or no effect on the histograms. 5-Hydroxytryptophan (5-HTP) had no effect on the nVPL neurons in morphine-naive rats, but in the morphine-dependent rats it renewed the ability of NRM stimulation to suppress the late activity. The tonic activity of the PAG neurons was significantly higher in morphine-dependent compared with that of the morphine-naive animals. Naloxone had a differential effect on the activity of the PAG neurons with regard to the two types of animals: it decreased the PAG activity drastically in the morphine-dependent rats. Apparently, the high tonic activity induced in the PAG by repeated administration of morphine acts on the descending antinociceptive fibers of the NRM and exhausts the synaptic transmitter substance, serotonin, in the NRM terminals, thus decreasing the ability of these terminals to block A-delta and C-fiber excitation of the STT. By assisting the synthesis of serotonin, 5-HTP renews the capacity of the NRM fibers to counteract STT excitation, and thus reinstates the normal function of the antinociceptive system.