Analgesic Action and Pharmacokinetics of Morphine and Diazepam in Man

Abstract

The analgesic actions of i.v. administered morphine, 0.14 mg/kg, diazepam, 0.14 mg/kg, and saline solution, 10 ml, were studied in 3 groups of volunteers by observing their responses to thermal stimulation for .apprx. 4 h. Serum concentrations of morphine, determined by radioimmunoassay, decreased with time from 30 min to 3 h, with a half life of .apprx. 120 min. Treatment of the data by traditional pain threshold techniques revealed a marked increase in the pain threshold in the group treated with morphine. Treatment of the data by nonparametric sencory decision theory revealed that morphine, and to a lesser extent diazepam, decreased discriminability, P(A), among the thermal stimuli. Apparently, less sensory information arrived centrally. Both drugs increased the subject''s response bias, B, fewer pain reports. The decrease in P(A) and the increase in B suggest that morphine and, to a lesser extent, diazepam, possess analgesic action. Subjects treated with saline injections showed no significant change in traditional pain threshold, discriminability or response bias over time. The changes in traditional pain threshold and sensory decision indices induced by morphine lasted at least 3 h after injection and did not correlate with the rapidly declining serum concentrations of morphine. The duration of analgesia was greater than that found clinically, presumably because the anxiety component was missing in experimental pain. The sensory, P(A), and psychological, B, components of sensory decision theory could prove useful in distinguishing between the analgesic and the mood-altering properties of analgesics used for the treatment of clinical pain.