Activation of CB1 and CB2 receptors attenuates the induction and maintenance of inflammatory pain in the rat.
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.
Elmes
Steven J R
SJR
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.
Winyard
Lisa A
LA
Medhurst
Stephen J
SJ
Clayton
Nick M
NM
Wilson
Alex W
AW
Kendall
David A
DA
Chapman
Victoria
V
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
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