Modulation of the micturition reflex pathway by intravesical electrical stimulation: an experimental study in the rat.

Intravesical electrical stimulation (IVES) is used clinically to improve bladder evacuation in patients with inadequate micturition contractions. The procedure involves field stimulation of Adelta bladder mechanoreceptor afferents resulting in a prolonged enhancement of the micturition reflex. The aim of the present experimental study in the rat was to identify the site for this neuromodulation, whether it was due to sensitization of bladder mechanoreceptors, to enhancement of transmission in the central micturition reflex pathway, or to improved effectiveness of the peripheral motor system of the bladder. The experiments were performed on female rats, anesthetized by alpha-chloralose. Multi-unit afferent or efferent activity was recorded from bladder pelvic nerve branches during repeated cystometries before and after IVES. The specific antagonist CPPene was used to block central glutaminergic receptors of NMDA type. Micturition threshold volume decreased significantly after IVES. The afferent threshold volume, peak response, and pressure sensitivity were unchanged as were the peak efferent activity and bladder contractility. There was no efferent activity until just before the micturition contraction. The IVES-induced decrease in micturition threshold was blocked by prior administration of the NMDA (N-methyl-D-aspartic acid) antagonist CPPene (3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphonic acid). The findings indicate that the IVES-induced modulation of the micturition reflex is due to an enhanced excitatory synaptic transmission in the central micturition reflex pathway. The observed modulation may account for the clinical beneficial effect of IVES treatment.