title: The alpha2A-adrenoceptor subtype is not involved in inflammatory hyperalgesia or morphine-induced antinociception.
abstract: The purpose of the present study was to investigate the role of the alpha(2A)-adrenoceptor subtype in inflammatory hyperalgesia, and in adrenergic-mu-opioid interactions in acute pain and inflammatory hyperalgesia. Behavioral responses to mechanical and thermal stimuli were studied in alpha(2A)-adrenoceptor knockout mice and their wild-type controls. Thermal nociception was evaluated as paw withdrawal latencies to radiant heat applied to the hindpaws. Mechanical nociception was measured using von Frey monofilament applications to the hindpaws. Mechanical and thermal hyperalgesia, induced with intraplantar carrageenan (1 mg/40 microl) were compared in alpha(2A)-adrenoceptor knockout and wild-type mice. The effects of the systemically administered mu-opioid receptor agonist morphine (1-10 mg/kg) were evaluated on mechanical withdrawal responses under normal and inflammatory conditions in knockout and wild-type mice. Withdrawal responses to radiant heat and von Frey monofilaments were similar in alpha(2A)-adrenoceptor knockout and wild-type mice before and after the carrageenan-induced hindpaw inflammation. Also, the antinociceptive effects of morphine in mechanical nociceptive tests were similar before and after carrageenan-induced hindpaw inflammation. Our observations indicate that alpha(2A)-adrenoceptors are not tonically involved in the modulation of inflammation-induced mechanical and thermal hyperalgesia. In addition, alpha(2A)-adrenoceptors do not appear to play an important role in mu-opioid receptor-mediated antinociception or antihyperalgesia.
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland.
authors.forename: Janne
authors.initials: J
authors.lastname: Lähdesmäki
authors.forename: Mika
authors.initials: M
authors.lastname: Scheinin
authors.forename: Antti
authors.initials: A
authors.lastname: Pertovaara
authors.forename: Heikki
authors.initials: H
authors.lastname: Mansikka
mesh_terms: D000698:Analgesia; D000818:Animals; D002351:Carrageenan / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced* / Q000150:complications / Q000188:drug therapy; D007249:Inflammation / Q000139:chemically induced* / Q000150:complications / Q000188:drug therapy; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009020:Morphine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects; D010147:Pain Measurement; D010812:Physical Stimulation; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000502:physiology
chemical_list: D018341:Receptors, Adrenergic, alpha-2; D017450:Receptors, Opioid, mu; D009270:Naloxone; D009020:Morphine; D002351:Carrageenan