Screening and Optimization of Nerve Targets and Parameters Reveals Inhibitory Effect of Pudendal Stimulation on Rat Bladder Hypersensitivity

BACKGROUND AND OBJECTIVESNeuromodulation has been reported to reliably improve symptoms of bladder overactivity and sometimes pain. The effect of electrical stimulation of several nerve pathways demonstrated to alter cystometric responses to bladder distension was examined on nociceptive responses in models of bladder hypersensitivity. METHODSBladder hypersensitivity was produced by several published methods including neonatal inflammation, acute inflammation, and chronic stress. Effects of different sites of stimulation (L6 and T13 nerve roots, proximal and distal pudendal nerves [PNs]) on nociceptive reflex responses to urinary bladder distension in urethane-anesthetized female rats were assessed and a parametric analysis of parameters of stimulation was performed. RESULTSBilateral biphasic stimulation of the proximal PNs resulted in statistically significant inhibition of visceromotor and cardiovascular responses to bladder distension in rats made hypersensitive by neonatal bladder inflammation. We found a range of optimal stimulation frequencies (5–10 Hz) which produced robust inhibitory effects when using short pulse widths (100–240 μs). Onset of inhibition was within minutes and persisted for several minutes after the stimulus was discontinued. Use of bilateral PN stimulation in acute inflammation and stress-induced hypersensitivity models as well as unilateral stimulation, very distal PN cutaneous branch stimulation, and stimulation of the T13 and L6 nerve roots all proved ineffective with the parameters used. CONCLUSIONSThis study suggests that inhibitory effects of bilateral PN stimulation can be evoked in a rodent hypersensitivity model at relatively low frequencies with short pulse widths. The onset of effect is rapid, which suggests the potential for treating episodic pain in painful bladder disorders.