Influence of naloxone on inhibitory pudendal-to-bladder reflex in cats

Abstract

To determine the involvement of opioid receptors in the inhibitory pudendal-to-bladder reflex, the effect of naloxone (0.01-1 mg/kg, i.v.), an opioid receptor antagonist, on the inhibition of bladder activity evoked by pudendal nerve stimulation was investigated in alpha-chloralose anesthetized cats. The inhibition of reflex isovolumetric bladder contractions induced by pudendal nerve stimulation (5-10 Hz) at intensity threshold (T) for producing complete inhibition was significantly suppressed by naloxone at a high dose (0.3 mg/kg). However, the inhibition elicited at higher intensities (1.5-3 T) was not changed. Naloxone (1 mg/kg) did not alter the frequency dependence of the inhibitory effect of pudendal stimulation. During cystometrograms (CMGs) pudendal nerve stimulation significantly increased bladder capacity to 155.1+/-24.5% and 163.4+/-10% of the control at stimulation intensities of 1 T and 1.5-3 T, respectively. After administration of naloxone (1 mg/kg), the bladder capacity during pudendal nerve stimulation at inhibition threshold (1 T) was not significantly different from control, but it was significantly increased at higher intensities (1.5-3 T). Naloxone alone markedly reduced bladder capacity to 43+/-11.1% of the control, and pudendal stimulation completely reversed this facilitatory effect. This study revealed that activation of opioid receptors contributes to or facilitates the inhibitory pudendal-to-bladder reflex. The reduction in bladder capacity after naloxone treatment also indicates that endogenous opioid peptides mediate a tonic inhibition of micturition. Understanding the neurotransmitter mechanisms involved in the inhibitory pudendal-to-bladder reflex could promote the development of new treatments for bladder overactivity and incontinence.