EFFECTS OF SYSTEMIC MORPHINE ON RESPONSES OF PRIMATES TO FIRST OR 2NDPAIN SENSATIONS

Despite evidence that systemic morphine preferentially attenuates seco nd pain sensations that are presumed to result from activation of unmy elinated (C) nociceptors, most animal models of nociception elicit sen sations that result from or are dominated by activation of myelinated (A-delta) nociceptors. Therefore, methods were developed to directly c ompare the effects of morphine on late (second) pain sensations and ea rly onset (first) pain sensations in an animal model. In order to esta blish appropriate stimulus parameters, human psychophysical experiment s compared characteristics of sensations evoked by brief(pulsed) therm al stimulation and ramp-and-hold thermal stimulation. Brief (500 msec) contact of a pre-heated thermode with the skin produced late pain sen sations with peripheral conduction velocities in the range of C affere nts, as estimated by latencies from stimulation of proximal and distal sites on the leg. The sensations evoked by brief contact increased wi th successive contacts (pulses) at 0.4 Hz, demonstrating temporal summ ation of sensation intensity. Pretreatment of the skin with capsaicin enhanced the late pain sensations from pulsed stimulation. In contrast , peak sensations evoked by ramp-and-hold thermal stimulation were evo ked at similar latencies from disparate sites on the leg, and capsaici n pretreatment of the skin did not increase the magnitude of these sen sations. The pulsed and ramp-and-hold forms of stimulation were used i n a paradigm designed to test for differential effects of systemic mor phine on operant responses of non-human primates. Low doses of morphin e reduced operant responding to pulsed thermal contact, while higher d oses were required to affect responses to ramp-and-hold thermal stimul ation. The low doses of morphine did not suppress non-nociceptive (int ertrial) motor responses, indicating that motor inhibition was not res ponsible for the effects on escape responses to pulsed stimulation. Me asurements of skin temperature 10 cm from the site of stimulation show ed that morphine had no effect on baseline temperature but attenuated changes in skin temperature that were elicited by pulsed and by ramp-a nd-hold stimulation. This effect of morphine on skin temperature respo nses could not account for the reduction of operant responsivity to th ermal stimulation. These results support previous findings that system ic morphine preferentially attenuates second pain sensations, and a ne w animal model of morphine-sensitive thermal nociception is establishe d. These findings demonstrate the importance of defining the sources o f afferent input and the response measures in experiments which attemp t to measure antinociceptive effects of pharmacological agents.