Effects of stimulation site and stimulation parameters on bladder inhibition by electrical nerve stimulation

What's known on the subject? and What does the study add? Electrical stimulation of the dorsal nerve of the penis, the compound pudendal nerve and the S1 sacral nerve have been used clinically to treat the symptoms of overactive bladder, but the relative efficacy of the three locations was unclear and the optimal stimulation parameters across locations had not been determined. In the present paper we quantified the effects of acute electrical stimulation location, frequency and amplitude on isovolumetric reflex bladder contractions and maximum cystometric capacity in anaesthetized male cats. Our results could influence the selection of anatomical targets for clinical neuromodulation and how neuromodulation devices are programmed.

To quantify the effects of acute electrical stimulation frequency and amplitude at the dorsal nerve of the penis (DNP), pudendal nerve (PN) and S1 sacral nerve (S1) on isovolumetric reflex bladder contractions and maximum cystometric capacity in anaesthetized male cats.

Experiments were conducted in 14 adult male cats anaesthetized with α-chloralose. The effects of stimulation on the pressure - time integral of reflex bladder contractions were evaluated using a randomized block design with the following factors randomized: stimulation intensity (0.8, 1, or 2 × the threshold for evoking a reflex electromyogram response in the external anal sphincter [T]), frequency (2 Hz, 5 Hz, 7.5 Hz, 10 Hz, 15 Hz, 20 Hz, or 33 Hz) and location (PN, S1 or DNP). The effects of stimulation (with parameters that produced maximum inhibition of isovolumetric bladder contractions) on cystometric capacity were evaluated using a randomized block design, with the order of stimulation location randomized and control trials interleaved with stimulation trials.

Inhibition of isovolumetric bladder contractions was significantly dependent on stimulation location, frequency, amplitude and the interactions between any two of these variables. Stimulation of the DNP, at 5 Hz, 7.5 Hz or 10 Hz, and at 2T caused greater reductions in normalized bladder contraction area than any other location, frequency or amplitude tested. Stimulation of the PN or S1 at 7.5 Hz or 10 Hz and 2T, or of the DNP at 5 Hz, 7.5 Hz or 10 Hz and 0.8T, 1T or 2T generated maximum inhibition of isovolumetric bladder contractions. Cystometric capacity was significantly larger with stimulation (10 Hz, 1T-2T) than control. There was no significant difference in cystometric capacity based upon stimulation location.

There was no significant difference in the maximum degree to which the respective optimum parameters inhibited bladder contractions or increased cystometric capacity by location. The range of amplitudes and frequencies that caused maximum inhibition was larger for DNP stimulation than for PN or S1 stimulation. These findings have implications on the selection of anatomical target and device programming for clinical neuromodulation for treatment of the symptoms of overactive bladder.