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

SS Negus, ER Butelman, Y Al and JH Woods

Department of Pharmacology, University of Michigan, Ann Arbor.

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.

Volume 266, Issue 3, pp. 1355-1363, 09/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics

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