title: Selective activation of cannabinoid CB(2) receptors suppresses spinal fos protein expression and pain behavior in a rat model of inflammation.
abstract: Activation of cannabinoid CB(2) receptors attenuates thermal nociception in untreated animals while failing to produce centrally mediated effects such as hypothermia and catalepsy [Pain 93 (2001) 239]. The present study was conducted to test the hypothesis that activation of CB(2) in the periphery suppresses the development of inflammatory pain as well as inflammation-evoked neuronal activity at the level of the CNS. The CB(2)-selective cannabinoid agonist AM1241 (100, 330 micrograms/kg i.p.) suppressed the development of carrageenan-evoked thermal and mechanical hyperalgesia and allodynia. The AM1241-induced suppression of carrageenan-evoked behavioral sensitization was blocked by the CB(2) antagonist SR144528 but not by the CB(1) antagonist SR141716A. Intraplantar (ipl) administration of AM1241 (33 micrograms/kg ipl) suppressed hyperalgesia and allodynia following administration to the carrageenan-injected paw but was inactive following administration in the contralateral (noninflamed) paw, consistent with a local site of action. In immunocytochemical studies, AM1241 suppressed spinal Fos protein expression, a marker of neuronal activity, in the carrageenan model of inflammation. AM1241 suppressed carrageenan-evoked Fos protein expression in the superficial and neck region of the dorsal horn but not in the nucleus proprius or the ventral horn. The suppression of carrageenan-evoked Fos protein expression induced by AM1241 was blocked by coadministration of SR144528 in all spinal laminae. These data provide evidence that actions at cannabinoid CB(2) receptors are sufficient to suppress inflammation-evoked neuronal activity at rostral levels of processing in the spinal dorsal horn, consistent with the ability of AM1241 to normalize nociceptive thresholds and produce antinociception in inflammatory pain states.
authors.affiliation: Neuroscience and Behavior Program, Department of Psychology, The University of Georgia, 30602, Athens, GA, USA.
authors.forename: A G
authors.initials: AG
authors.lastname: Nackley
authors.forename: A
authors.initials: A
authors.lastname: Makriyannis
authors.forename: A G
authors.initials: AG
authors.lastname: Hohmann
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001892:Camphanes / Q000494:pharmacology; D002186:Cannabinoids / Q000494:pharmacology*; D002351:Carrageenan / Q000494:pharmacology; D004195:Disease Models, Animal; D004347:Drug Interactions / Q000502:physiology; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009619:Nociceptors / Q000187:drug effects* / Q000378:metabolism; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077285:Rimonabant
chemical_list: C439263:AM 1241; D000700:Analgesics; D001892:Camphanes; D002186:Cannabinoids; C469526:Cnr2 protein, rat; D010880:Piperidines; D016760:Proto-Oncogene Proteins c-fos; D011720:Pyrazoles; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C110630:SR 144528; D002351:Carrageenan; D000077285:Rimonabant