Administration of endocannabinoids prevents a referred hyperalgesia associated with inflammation of the urinary bladder

Background: Referred hyperalgesia to a somatopically appropriate superficia l site is a cardinal symptom of visceral inflammatory pain and has been dem onstrated after turpentine-induced urinary bladder inflammation in the rat. The authors examined the effect of the endocannabinoids anandamide and pal mitoylethanolamide oil the referred hyperalgesia associated with this model . Methods After measurement of baseline limb withdrawal latencies to a noxiou s heat stimulus, the bladders of 50 female Wistar rats mere inflamed by int ravesical administration of 0.5 ml 50% turpentine. Ten or 25 mg/kg of anand amide or palmitoylethanolamide or vehicle were administered immediately bef ore introduction of turpentine, Antagonists to both the cannabinoid CB1 and CB2 receptors mere coadministered with the higher dose of endocannabinoids . Latencies were recorded 2, 4, 6, 8, and 24 h after removal of turpentine. The difference between fore limb and hind limb withdrawal latencies was pl otted against time, and areas under these curves were compared. Results: Inflammation of the urinary bladder was associated with a relative thermal hyperalgesia referred to the hind limb. Anandamide and palmitoylet hanolamide attenuated this referred;hyperalgesia at doses of 10 and 25 mg/k g, The CB, receptor antagonist SR141716A reduced the antihyperalgesic effec t of anandamide, but the CB, antagonist SR144528 did not. Coadministration of SR141716A with palmitoylethatlolamide did not affect the antihyperalgesi c effect but was reduced by SR144528. Conclusions: Anandamide (via CB1 receptors) and palmitoylethanolamide (puta tively via CB, receptors) attenuated a referred hyperalgesia in a dose-depe ndent fashion. CB, and CB, receptors are strategically situated to influenc e the nerve growth factor-driven referred hyperalgesia associated with infl ammation of the urinary bladder. These data implicate cannabinoids as a nov el treatment for vesical pain,