Antinociceptive Interactions Between Alphha2-Adrenergic and Opiate Agonists at the Spinal Level in Rodents

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Abstract
R systemic naloxone, an opioid antagonist. The effect of, tolerance to systematically administered morphine on responses to i.t. morphine and clonidine was examined in mice. Antinociception was determined by observing tin response to a clamp applied to the tail (Haffner test) in mice and by the tail-flick test in rats; log dose-response curves for antinociception were generated for morphine, clonidine, and each drug combination. Morphine and clonidine both produced dose-dependent antinociception when given i.t. in both species. The i.t. administration of yohimbine attenuated the antinociceptive effect of both clonidine and morphine, but naloxone attenuated only the response to morphine. Further, a sub-analgetic dose of i.t. clonidine potentiated the effect of i.t. morphine. In morphine-tolerant mice, i.t. morphine urns not efficacious whereas clonidine retained full efficacy, although potency urns slightly diminished. Thus, it appears that α2 adrenoceptor-mediated antinociception is independent of opiate receptor mechanisms. Clinical use of intrathecal combinations of α2,adrenergic and opiate receptor agonists to increase analgesia and use of intrathecal α2, agonists for pain relief in patients tolerant to opiates might deserve evaluation. Address correspondence to Dr. Ossipov, Anaquest, BOC Health Care, 100 Mountain Avenue, Murray Hill, NJ 07974. Accepted for publication September 19, 1988. © 1989 International Anesthesia Research Society...