title: Activation of CB1 and CB2 receptors attenuates the induction and maintenance of inflammatory pain in the rat.
abstract: The aim of the present study was to investigate the effects of cannabinoid agonists on established inflammatory hyperalgesia. We have compared the effects of pre-administration versus post-administration of a potent non-selective cannabinoid agonist HU210 and a selective CB2 receptor agonist JWH-133 on hindpaw weight bearing and paw oedema in the carrageenan model of inflammatory hyperalgesia. For comparative purposes we also determined the effects of the mu-opioid receptor agonist morphine and the COX2 inhibitor rofecoxib in this model. At 3 h following intraplantar injection of carrageenan (2%, 100 microl) there was a significant (P < 0.001) reduction in weight bearing on the ipsilateral hindpaw, compared to vehicle treated rats and a concomitant increase in ipsilateral hindpaw volume (P < 0.001), compared to vehicle treated rats. Systemic administration of HU210 (10 microg/kg) and JWH-133 (10 mg/kg) at 3 h following injection of carrageenan, significantly attenuated decreases in ipsilateral hindpaw weight bearing (P < 0.05 for both) and paw volume (P < 0.001 for both). Pre-administration of HU210 and JWH-133 had similar effects on weight bearing in this model. Pre-administered HU210 also significantly decreased carrageenan-induced changes in paw volume (P < 0.001), this was not the case for JWH-133. Effects of post-administered HU210 and JWH-133 on ipsilateral hindpaw weight bearing and paw volume were comparable to the effect of systemic post-administration of morphine and rofecoxib (3 mg/kg for both). In summary, both HU210 and JWH-133 attenuated established inflammatory hypersensitivity and swelling, suggesting that cannabinoid-based drugs have clinical potential for the treatment of established inflammatory pain responses.
authors.affiliation: Institute of Neuroscience, School of Biomedical Sciences, E Floor, Medical School, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK Neurology and GI CEDD, GlaxoSmithKline, Third Avenue, Harlow, Essex CM19 5AW, UK.
authors.forename: Steven J R
authors.initials: SJR
authors.lastname: Elmes
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Winyard
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Medhurst
authors.forename: Nick M
authors.initials: NM
authors.lastname: Clayton
authors.forename: Alex W
authors.initials: AW
authors.lastname: Wilson
authors.forename: David A
authors.initials: DA
authors.lastname: Kendall
authors.forename: Victoria
authors.initials: V
authors.lastname: Chapman
mesh_terms: D000700:Analgesics / Q000008:administration & dosage; D000818:Animals; D002186:Cannabinoids / Q000008:administration & dosage*; D002351:Carrageenan; D013759:Dronabinol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004338:Drug Combinations; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D007249:Inflammation / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists*; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists*; D016896:Treatment Outcome; D016474:Weight-Bearing
chemical_list: D000700:Analgesics; D002186:Cannabinoids; C469526:Cnr2 protein, rat; D004338:Drug Combinations; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D013759:Dronabinol; D002351:Carrageenan; C062018:HU 211; C432747:1,1-dimethylbutyl-1-deoxy-Delta(9)-THC