Prostaglandin E2-induced thermal hyperalgesia and its reversal by morphine in the warm-water tail-withdrawal procedure in rhesus monkeys.

Four monkeys were seated in primate restraint chairs and the terminal 10 cm of their shaved tails were dipped into water maintained at a series of temperatures ranging from 38-54 degrees C. The latency to tail withdrawal from several temperatures was measured and temperature-effect curves for each monkey were generated. When administered s.c. into the tail, prostaglandin E2 (PGE2; 0, 1.58, 5.0 and 15.8 micrograms) produced a dose-dependent hyperalgesia manifested as dose-dependent leftward shifts in the temperature-effect curves. This hyperalgesia peaked 15 to 45 min after administration and lasted for approximately 2 hr. PGE2-induced hyperalgesia was mediated locally, because administration of 15.8 micrograms of PGE2 into the back had no effect on the temperature-effect curve. The hyperalgesic effects of PGE2 were reversed potently by morphine (0.32-3.2 mg/kg), and the effects of morphine were antagonized in a surmountable manner by both the opioid antagonist quadazocine (0.1 mg/kg) and by systemic administration of the charged opioid antagonist quaternary naltrexone (3.2 mg/kg). These results indicate that PGE2 produces thermal hyperalgesia in rhesus monkeys and also suggests that this hyperalgesia may be reversed by activation of peripheral opioid receptors. PGE2-induced hyperalgesia in the warm-water tail-withdrawal procedure may provide a useful assay for evaluating the effects of pharmacological and nonpharmacological treatments on hyperalgesia associated with inflammation in primates.