Differential effects of α2-adrenoceptors in the modulation of the thermoregulatory response in mice induced by meperidine

Abstract

Background: Meperidine proved to be more effective in treatment of shivering than equianalgesic doses of other opioids, especially pure μ-agonists. Further, meperidine has well known nonopioid actions including agonistic effects at α2-adrenoceptors in vitro. Accordingly, the authors investigated nonopioid receptor-mediated effects of meperidine on thermoregulation using a mice model of nonshivering thermogenesis. To differentiate conceivable α2-adrenoceptor subtype specific interactions the authors analyzed wild-type mice and knock-out mice with deletion of the α2A-, α2B-, or α2C-adrenoceptor. Methods: Ten mice per group (n = 60) were injected with saline, meperidine (20 mg/kg), saline plus naloxone (125 μg/kg), meperidine plus naloxone, fentanyl (50 μg/kg) plus naloxone, or meperidine plus atipamezole (2 mg/kg) intraperitoneally. Each mouse was subjected to the six different treatments. Then they were positioned into a plexiglas chamber where rectal temperature and mixed expired carbon dioxide were measured while whole body cooling was performed. Maximum response intensity and thermoregulatory threshold temperature of nonshivering thermogenesis were analyzed. Results: Meperidine decreased the thermoregulatory threshold temperature in wild-type mice and α2B- and α2C-adrenoceptor knock-out mice. This effect ended after injection of the α2-adrenoceptor antagonist atipamezole. In wild-type and α2B-adrenoceptor knock-out mice, the decrease of thermoregulatory threshold was not reversible by administration of the opioid receptor antagonist naloxone. In contrast, in α2A- adrenoceptor knock-out mice, no decline of thermoregulatory threshold following meperidine injection was detectable. Maximum response intensity of nonshivering thermogenesis was comparable in all groups. Conclusions: The authors' results suggest a major role of α2-adrenoceptors, especially the α2A subtype, in the mediation of thermoregulatory effects caused by meperidine in mice. Copyright © 2008 The American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.