TRPA1 Agonists and Bladder Nociception in Female Rats Suggest Potential for Nutraceutical Benefit from Cinnamon

Abstract

TRPA1-related drugs alter sensation, particularly in conditions of inflammation. To further characterize the role of these drugs in bladder sensation, the TRPA1 agonist cinnamaldehyde (CMA) and oral true cinnamon spice were examined in preclinical models of bladder pain. Female adult rats, with and without acute zymosan-induced cystitis, were anesthetized and visceromotor (VMR) and cystometric responses to urinary bladder distension (UBD) were determined following either the intravesical administration of CMA/vehicle solutions or the oral administration of true cinnamon/vehicle. ELISA measures of bladder TRPA1 content were also determined. Acute cystitis resulted in increases in bladder TRPA1 content and produced an increased vigor of the VMRs to UBD and a lowering of micturition volume thresholds for activation of a micturition response. Intravesical CMA produced a robust inhibition of VMRs to UBD in rats with cystitis but not in those without. Micturition volume thresholds were lowered by CMA in rats without cystitis but had no additional effect in rats with cystitis. Oral cinnamon also produced a robust inhibition of VMRs to UBD in rats with cystitis and a mild augmentation of VMRs to UBD in rats without cystitis. A potentially analgesic effect of the spice, true cinnamon, in the treatment of the pain of acute cystitis was suggested by these preclinical studies. Human studies are indicated.