1. Activation of CB1 and CB2 receptors attenuates the induction and maintenance of inflammatory pain in the rat.
- Author
-
Elmes SJR, Winyard LA, Medhurst SJ, Clayton NM, Wilson AW, Kendall DA, and Chapman V
- Subjects
- Analgesics administration & dosage, Animals, Carrageenan, Dronabinol administration & dosage, Drug Combinations, Hyperalgesia etiology, Hyperalgesia prevention & control, Inflammation chemically induced, Inflammation complications, Inflammation physiopathology, Male, Rats, Treatment Outcome, Weight-Bearing, Cannabinoids administration & dosage, Dronabinol analogs & derivatives, Hyperalgesia drug therapy, Hyperalgesia physiopathology, Inflammation drug therapy, Receptor, Cannabinoid, CB1 agonists, Receptor, Cannabinoid, CB2 agonists
- 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.
- Published
- 2005
- Full Text
- View/download PDF