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.