The role of μ-opioid receptors in inflammatory hyperalgesia and α2-adrenoceptor-mediated antihyperalgesia

The purpose of the present study was to investigate the role of μ-opioid receptor in inflammatory hyperalgesia in intact and in spinalized animals and the interaction between μ-opioid and α2-adrenergic receptor in acute pain and inflammatory hyperalgesia. Behavioral responses to mechanical and heat stimuli were studied in μ-opioid receptor knockout mice and wildtype control mice. Thermal nociception was evaluated by measuring paw withdrawal latencies to radiant heat applied to the hindpaws. Mechanical nociception was measured by von Frey monofilament applications to the hindpaws. Intraplantar carrageenan-induced (1 mg/40 μl) mechanical and heat hyperalgesia were compared in μ-opioid knockout and wildtype mice. The effect of systemically administered α2-adrenergic receptor agonist dexmedetomidine (1-10 μg/kg) was evaluated on mechanical and thermal withdrawal responses under normal and inflammatory state in knockout and wildtype mice. The role of μ-opioid receptor in descending modulation of nociception was studied by assessing mechanical and heat withdrawal responses before and after mid-thoracic spinalization. Withdrawal responses to radiant heat and von Frey monofilaments were similar in μ-opioid knockout and wildtype mice before and after the carrageenan induced hindpaw inflammation. Also, antinociceptive effects of dexmedetomidine in thermal and mechanical nociceptive tests were similar before carrageenan induced hindpaw inflammation. However, the potency of dexmedetomidine was significantly reduced in carrageenan-induced mechanical hyperalgesia in μ-opioid knockout mice compared to the wildtype control mice. Thermal and mechanical withdrawal responses were similar between μ-opioid knockout and wildtype mice before and after mid-thoracic spinalization. Our observations indicate that the μ-opioid receptors do not play an important role in α2-adrenergic receptor agonist-mediated acute antinociception. In addition, μ-opioid receptors are not tonically involved in the modulation of inflammation-induced mechanical and thermal hyperalgesia, and the supraspinal control of spinal reflexes. However, in the presence of inflammation, μ-opioid receptors play an important role in the antihyperalgesic actions of an α2-adrenergic receptor agonist.