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 α-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.

A spinal GABAergic mechanism is necessary for bladder inhibition by pudendal afferent stimulation

“…Post hoc paired comparisons with Bonferroni correction showed that while normalized bladder pressure was significantly higher with picrotoxin (*P Ͻ 0.001), there was no significant difference between control, paralytic, and washout trials. contributions of opioidergic mechanisms to stimulationevoked bladder inhibition (7,28). The present results reveal that a spinal GABAergic mechanism mediates the inhibitory pudendovesical pathway.…”

“…To block glycinergic receptors, increasing cumulative doses of strychnine (n ϭ 4, 0.01-0.1 mg/kg iv) were administered, including to two animals who received cumulative doses up to 0.25 mg/kg iv (40). Increasing cumulative doses of naloxone (0.1-4.0 mg/kg iv), a competitive opioid antagonist, were administered to identify any opioidergic contribution to bladder inhibition (n ϭ 3), as this was ambiguous from prior studies (7,28).…”

Electrical stimulation for the treatment of lower urinary tract dysfunction after spinal cord injury

“…132 Opioids were also found to contribute to the inhibitory pudendal-to-bladder reflex in cats. 133 In similar experiments, opioids were found to play a differential role in inhibition of nociceptive and non-nociceptive bladder contractions by tibial nerve stimulation. 134 Other experiments have demonstrated that metabotropic glutamate 5 receptors, 135,136 and serotoninergic receptors, 137 which may interact with opioid mechanisms, are involved in bladder inhibition by PNS and that the effects are primarily mediated by spinal, not supraspinal, processes.…”

Potential Use of Pudendal Nerve Stimulation for Voiding Dysfunction

“…The inhibitory pudendal-bladder reflex that promotes bladder storage is thought to be mediated by inhibitory neurotransmitters including glycine, γ-aminobutyric acid, and possibly enkephalins/opioid peptides. Chen et al [15] recently investigated the role of enkephalins in the pudendalbladder reflex by using an opioid receptor antagonist and pudendal nerve stimulation in cats. The researchers remarked that there was an intensity-and frequencydependent effect of pudendal nerve stimulation; a low frequency (5-10 Hz) suppressed isovolumetric bladder contractions, whereas a higher frequency or even lower frequency (1-3 Hz) facilitated bladder contraction, although not consistently.…”

“…The ultimate conclusion was that opioid receptors at least partially contribute to inhibition of reflex bladder activity by pudendal nerve stimulation. When the antagonist was given, the inhibition of reflex bladder activity was reduced, although it could be overcome by increasing the intensity of stimulation [15].…”