Effect of systemic morphine on the responses of convergent neurons to noxious heat stimuli applied over graded surface areas

Background Stimulus intensity is a major determinant of the antinociceptive activity of opiates. This study focused on the influence of the spatial ch aracteristics of nociceptive stimuli, on opiate-induced depressions of noci ceptive transmission at the level of the spinal cord. Methods: Anesthetized rats were prepared to allow extracellular recordings to be made from convergent neurons in the lumbar dorsal horn. The effects o f systemic morphine (1 and 10 mg/kg) were compared with those of saline for thermal stimuli of constant intensity, applied to the area of skin surroun ding the excitatory receptive field (1.9 cm(2)) or to a much larger adjacen t area (18 cm(2)), Results: The responses (mean +/- SD) elicited by the 1.9-cm(2) stimulus wer e not modified by 1 mg/kg intravenous morphine, although they were decrease d by the 10-mg/kg dose (to 11 +/- 4% of control values compared with saline ; P < 0.05), In contrast, when the 18-cm(2) stimulus was applied, 1 mg/kg i ntravenous morphine produced a paradoxical facilitation of the neuronal res ponses (159 +/- 36% of control values; P < 0.05) and 10 mg/kg intravenous m orphine resulted in a weaker depression of the responses (to 42 +/- 24% of control values; P < 0.05) than Tvas observed with the smaller stimulus. Conclusions: Doses of systemic morphine in the analgesic range for rats had dual effects on nociceptive transmission at the level of the spinal cord, depending on the surface area that was stimulated Such effects are difficul t to explain in terms of accepted pharmacodynamic concepts and may reflect an opioid-induced depression of descending inhibitory influences triggered by spatial summation.