Effects of Endocannabinoids on Referred Hyperalgesia in the Rat Investigated.Farquhar-Smith and Rice(page 507)
Using an established model of turpentine-induced urinary bladder inflammation, Farquhar-Smith and Rice investigated the effect of administration of the endocannabinoids anandamide and palmitoylethanolamide on referred hyperalgesia in the rat. The investigators first measured limb withdrawal latencies to thermal stimulus (baseline) in 50 female Wistar rats. Bladder inflammation was provoked by instillation of turpentine (0.5 ml, 50%, in olive oil) via urethral catheters. Then, the rats were assigned randomly to 1 of 10 groups. Twenty animals divided into four groups of five were assigned to administration of 25 mg/kg anandamide, an equivalent volume of soya emulsion vehicle control, 25 mg/kg palmitoylethanolamide, or an equivalent volume of a 2:3 vehicle control of dimethyl sulphoxide–saline via the intraperitoneal route. Two other groups (five animals each) were assigned to administration of 10 mg/kg of either anandamide or palmitoylethanolamide, also via the intraperitoneal route. The last four groups of animals (n = 5) were assigned to administration of higher doses of either endocannabinoid coadministered with one of two receptor antagonists.
Latencies to withdrawal of hind limbs to thermal stimuli were recorded 2, 4, 6, 8, and 24 h after removal of turpentine, with the forepaw latencies of each animal serving as control measurements. At doses of 10 and 25 mg/kg, both anandamide and palmitoylethanolamide attenuated the referred hyperalgesia in the hind limbs of the rats after bladder inflammation. The CB1receptor antagonist SR14176A reduced the antihyperalgesic effect of anandamide, but the CB2antagonist SR144528 did not. Coadministration of SR141716A with palmitoylethanolamide did not affect the antihyperalgesic effect but was reduced by SR144528. CB1and CB2receptors, the investigators state, are situated strategically to influence the nerve growth factor–driven referred hyperalgesia associated with inflammation of the urinary bladder.