Variable patterned pudendal nerve stimuli improves reflex bladder activation

Abstract

We evaluated variable patterns of pudendal nerve (PN) stimuli for reflex bladder excitation. Reflex activation of the bladder has been demonstrated previously with 20-33 Hz continuous stimulation of PN afferents. Neuronal circuits accessed by afferent mediated pathways may respond better to physiological patterned stimuli than continuous stimulation. Unilateral PN nerve cuffs were placed in neurologically intact male cats. PN stimulation (0.5-100 Hz) was performed under isovolumetric conditions at bladder volumes up to the occurrence of distension evoked reflex contractions. Stimulus evoked reflex bladder contractions were elicited in eight cats. Across all experiments, bursting of 2-10 pulses at 100-200 Hz repeated at continuous stimulation frequencies evoked significantly larger bladder responses than continuous (single pulse) stimulation (52.0+/-44.5%). Bladder excitation was also effective at 1 Hz continuous stimuli, which is lower than typically reported. Variable patterned pulse bursting resulted in greater evoked reflex bladder pressures and increased the potential stimulation parameter space for effective bladder excitation. Improved bladder excitation should increase the efficacy of neuroprostheses for bladder control.

Fig. 1

(a) Schematic representation of variable “burst” stimulus pattern. Nomenclature: pw = pulse width; #_P = number of pulses; f_PU = pulse frequency; f_TR = train rate frequency. (b) Example traces for continuous (e.g., 33 Hz) and burst (e.g., 2 × 200 Hz @ 33 Hz) stimulation.

Fig. 2

Example of stimulus evoked bladder contraction, for a low-frequency bursting stimulus pattern (5 × 200 Hz @ 1 Hz). Measured parameters: P_BASE–AVE = 3 s pressure average prior to stimulus initiation; P_BASE–SD = 3 s pressure standard deviation prior to stimulus initiation; EVAL_TH = P_BASE–AVE + 3 · P_BASE–SD; P_AVE = av-erage pressure while above EVAL_TH(duration noted by horizontal line in figure); P_MAX = maximum pressure while above EVAL_TH; P_AVE–EV P_AVE – P_BASE–AVE; P_MAX–EV = P_MAX – P_BASE–AVE.

Fig. 3

Effective continuous stimulation frequencies for bladder activation. Average evoked pressures (P_AVE–EV) at 0.5, 1, 5, 10, 20, 33, and 50 Hz train rate frequencies (f_TR), for one pulse (#_P). Large squares indicate results averaged across all trials performed, with pooled standard deviations as error bars. Smaller icons at each frequency represent averages from individual experiments.

Fig. 4

Pulse bursting increased evoked pressure over continuous single pulse stimuli in every experiment. The multipulse stimulus parameter combination in each experiment that resulted in the largest evoked pressure was used for comparison. In each experiment, the average and standard deviation (error bars) of the average evoked pressure for single and multiple pulse stimulus patterns are normalized to the mean average evoked pressure for the single pulse stimulus pattern. Continuous stimulation frequencies were 1 Hz for lower frequency responders and 33 Hz for higher frequency responders. Bursting stimulation patterns were 5 × 100/200 Hz @ 1 Hz for lower frequency responders 1, 2, 3, and 5, and 10 × 100/200 @ 1 Hz for lower frequency responder 4. Bursting stimulation patterns were 2 × 200 Hz @ 20, 25, and 33 Hz for higher frequency responders 1, 2, and 3, respectively. Asterisks indicate experiments in which average pressures were significantly different (p < 0.05), using student's t-test. The evoked pressure increase average across experiments was also significantly different (p < 0:005), according to a t-test for two dependent samples. The standard deviation for bursting stimulation in lower frequency responder #1 was 123%.

Fig. 5

Contour plots of average evoked pressure (P_AVE–EV) against number of pulses (#_P) and train rate frequency (f_TR), for (a) lower frequency responding and (b) higher frequency responding experiments. Preferred ranges indicate that the addition of pulses results in greater evoked pressures than that evoked by continuous frequency stimulation at #_P = 1. The dots indicate locations of stimulus parameter combinations that were included; 280 trials across 27 stimulus parameter combinations in (a) and 293 trials across 47 stimulus parameter combinations in (b). The region outside the solid line indicates the limit of the parameter space where adding pulses leads to a continuous stimulation frequency, equal to or greater than the pulse frequency (f_PU), for a pulse frequency of 200 Hz.