The role of mu-opioid receptors in inflammatory hyperalgesia and alpha 2-adrenoceptor-mediated antihyperalgesia.
The purpose of the present study was to investigate the role of mu-opioid receptor in inflammatory hyperalgesia in intact and in spinalized animals and the interaction between mu-opioid and alpha2-adrenergic receptor in acute pain and inflammatory hyperalgesia. Behavioral responses to mechanical and heat stimuli were studied in mu-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 microl) mechanical and heat hyperalgesia were compared in micro-opioid knockout and wildtype mice. The effect of systemically administered alpha2-adrenergic receptor agonist dexmedetomidine (1-10 microg/kg) was evaluated on mechanical and thermal withdrawal responses under normal and inflammatory state in knockout and wildtype mice. The role of micro-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 mu-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 mu-opioid knockout mice compared to the wildtype control mice. Thermal and mechanical withdrawal responses were similar between mu-opioid knockout and wildtype mice before and after mid-thoracic spinalization. Our observations indicate that the mu-opioid receptors do not play an important role in alpha2-adrenergic receptor agonist-mediated acute antinociception. In addition, micro-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, mu-opioid receptors play an important role in the antihyperalgesic actions of an alpha2-adrenergic receptor agonist.
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA. heikki.mansikka@tyks.fi
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H
Mansikka
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Zhou
D M
DM
Donovan
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Pertovaara
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Raja
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002351:Carrageenan; D003655:Decerebrate State; D020927:Dexmedetomidine / Q000494:pharmacology; D005528:Foot; D006614:Hindlimb; D006358:Hot Temperature; D006930:Hyperalgesia / Q000209:etiology* / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000150:complications*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009619:Nociceptors / Q000187:drug effects; D010812:Physical Stimulation; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000502:physiology*; D012016:Reference Values
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D011942:Receptors, Adrenergic, alpha; D017450:Receptors, Opioid, mu; C050701:atipamezole; D020927:Dexmedetomidine; D002351:Carrageenan