The capsaicin analogue SDZ249-665 attenuates the hyper-reflexia and referred hyperalgesia associated with inflammation of the rat urinary bladder

This study assessed the effects of the systemically administered capsaicin analogue SDZ249-665 in an animal model of visceral pain and hyper-reflexia. The effects: of prophylactic administration of SDZ249-665 (in the dose ran ge 0.05-1 mg/kg) on the viscero-visceral hyperreflexia (VVH) and the referr ed viscero-somatic hyperalgesia to mechanical stimuli (VSH) associated with turpentine inflammation of the rat urinary bladder were evaluated. SDZ249- 665 attenuated both the VVH and the VSH in a dose related fashion. In the V VH model, following solvent control administration, intra-vesical turpentin e administration was associated with a significant reduction in micturition threshold to 43.7% (SEM 6.3) of baseline, indicating the presence of a VVH . This effect was not observed when animals were prophylactically treated w ith SDZ249-665 alone. At a dose of 0.1 mg/kg the micturition threshold was 90.7% (SEM 10.2) of baseline at 1 h after intra-vesical instillation of tur pentine. In the VSH model, curves were plotted of the difference in fore an d hind limb withdrawal latencies from a mechanical stimulus and the area un der these curves (AUCs) were compared between different treatment protocols . Intra-vesical turpentine was associated with a negative deflection of the curve (AUC -5.2 x 10(3) SEM 1.7) in comparison with naive animals (AUC -0. 02 x 10(3) SEM 0.6), indicative of a referred hyperalgesia. This was preven ted, in a dose-related manner, by prophylactic administration of SDZ249-665 . For example, at a dose of 0.5 mg/kg the AUC was +0.4 x 10(3) (SEM 0.8). T hese findings support previous wort indicating that capsaicin sensitive neu rones participate in patho-physiological events occurring following inflamm ation of the bladder, and provides evidence that systemically active capsai cin based compounds may be developed for use in the clinical setting. (C) 2 001 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.