1) 2 Hz sacral nerve stimulation was more effective than 14 Hz stimulation at reversing changes in anal evoked potentials caused by pudendal nerve injury in a rodent model. 2) While 14 Hz stimulation restored evoked potentials to baseline levels after injury, 2 Hz stimulation potentiated potentials beyond baseline levels. 3) Therefore, lower stimulation frequencies like 2 Hz may be more effective in improving anal sensation in patients with fecal incontinence compared to the standard 14 Hz frequency currently used.

1. 2 Hz sacral nerve stimulation is more effective than 14 Hz in reversing changes in anal evoked potentials caused by
pudendal nerve injury in a rodent model
Evers J1, O’Connell PR1,2, Jones JFX1
1School of Medicine and Medical Science, University College Dublin, Dublin, Ireland
2Centre for Colorectal Disease, St Vincent’s University Hospital, Dublin, Ireland
Abstract
The common clinical stimulation frequency in sacral nerve stimulation (SNS) may not be the optimal one. Therefore, this study compares the efficacy of 2Hz SNS, as was previously shown to be most effective in the potentiation of anal evoked potentials (EPs) in the rat (Evers et al., 2014), to restore anal EPs diminished by pudendal nerve injury in a rodent model. While 14Hz SNS restored EPs to their baseline, 2Hz SNS potenti- ated EPs well beyond baseline. Therefore, 2Hz SNS may be more effective in improving anal sensation in faecal incontinence (FI) patients.
Methods
Thirty-two female nulliparous Wistar rats (body mass: 189g-268g) were used in this study. Experiments were carried out in accordance to protocols approved by the UCD Animal Ethics Research Committee and licenced by the Irish Department of Health and Children. Experiments were performed under urethane an- aesthesia (1.5g*kg-1, i.p.) and vital signs were stable throughout the procedure. Four groups (N=8) were studied: Balloon control, Sham, 2Hz SNS and 14Hz SNS. A craniotomy was performed over the right pri- mary somatosensory cortex. A flexible 32-channel multi-electrode array, placed extra-durally, recorded EPs created by electrical anal canal stimulation. A laparotomy was performed and two Foley catheters were inserted in the retro-uterine space. The balloons were inflated (1.5ml each) for 60min. SNS was per- formed utilizing a custom made rodent lead (Medtronic Inc.) placed in the left first sacral foramen and ap- plied at the motor threshold (5.6V±0.7V), 2 or 14Hz and 1ms pulse duration for 10min. EPs were recorded every 10min before, during and after balloon inflation. Values were expressed as a percentage of the baseline value. A two-way repeated-measures ANOVA and Bonferroni post-test were used for analysis. All values are expressed as mean ± sem; the criterion for statistical significance was P<0.05.
Introduction
Although SNS is commonly used in the treatment of FI, when conservative treatment options fail, on an in- tention-to-treat basis it is successful only in 58% of patients (< 50% reduction in incontinence episodes; Thin et al., 2013). Optimisation of stimulation parameters, like stimulation frequency, may improve treatment out- come. Our group has previously shown, that SNS at 2Hz maximally potentiates anorectal inputs to the so- matosensory cortex in a rodent model (Evers et al., 2014). This study compares the potency of 2Hz and the clinically used 14Hz stimulation in an acute rodent model of childbirth related FI.
Conclusion
This study has demonstrated, that (1) pudendal nerve injury caused by intra-pelvic balloon inflation reduces anal EP amplitude; (2) SNS applied after the injury occurred restores anal EP amplitude; (3) 2Hz SNS is more effective in ameliorating EP amplitude than 14Hz SNS. Therefore, a reduction in stimulation frequency may improve treatment outcomes in SNS.
Results
Anal EPs consisted of one upwards deflection followed by a less marked downwards deflection with an onset latency of 10.3ms±0.4ms and an amplitude of 52.1μV±4.4μV. During balloon inflation EP ampli- tudes decreased to -69%±7% in the balloon control group, to -73%±6% in the 14Hz group and to -64% ±5% in the 2Hz group. In the balloon control group EPs recovered to -35%±2% after balloon deflation. Compared to the balloon control group EPs during the recovery period were increased by SNS. 14Hz stimulation increased EPs to –3%±4% and 2Hz stimulation increased EPs to 33%±4%. Evoked potential amplitude in the Sham group was stable; the coefficient of variation for one animal over the 150min was 7%±1%. A two-way repeated-measures ANOVA showed that groups were significantly different (Treatment factor: P<0.0001, Time factor: P<0.0001, Interaction: P<0.0001). A Bonferroni post-test showed that in all groups with balloon inflation (balloon control, 14Hz SNS and 2Hz SNS group) EP ampli- tude was diminished during balloon inflation compared to the Sham group. The response to balloon infla- tion in these three groups was not significantly different.
The recovery period (100-150min) was analysed separately to study the effect of SNS. The results of a two-way repeated-measures ANOVA showed that the Treatment factor (P<0.0001) was highly significant (Time factor: P=0.36, interaction: P=0.91). A Bonferroni post-test confirmed that compared to the balloon control group 14Hz and 2Hz increased EP amplitude. Evoked potentials in the 2Hz SNS groups had a larger amplitude than EPs in the 14Hz group and Sham group (P=0.05), while EPs in the 14Hz and Sham group were not significantly different.
Acknowledgements
The authors wish to acknowledge the support of
Science Foundation Ireland and Medtronic.
References
Evers J, Devane L, Carrington EV, Scott SM, et al., The effect of stimulation frequency and intensity in sacral neuromodulation on anorectal inputs to the somatosensory cortex. BJS 2014 Sep;101(10):1317-28.
Thin NN, Horrocks EJ, Hotouras A, Palit S, et al. Systematic review of the clinical effectiveness of neuromod- ulation in the treatment of faecal incontinence. The British journal of surgery. 2013;100(11):1430-47.
Peirce C, O'Herlihy C, O'Connell PR, Jones JF. Effect of injury on S1 dorsal root ganglia in an experimental model of neuropathic faecal incontinence. BJS 2011;98(8):1155-9.
Figure 2
Study design. Timeline and in- terventions in the 4 groups.
Figure 4 Group traces (N=8) and representative col- our maps at base- line, after 60min balloon inflation and during the re- covery period from the 14Hz (A) and 2Hz restoration groups (B). Colour maps encode the maximal ampli- tude.
Figure 1 A. Experimental set-up. B. Sketch illustrating the balloon model. Deflated and inflated bal- loons (Bal), uterus (U), rectum (R) and anal canal (AC)) are shown. C. Relationship between percent increase in EP amplitude after SNS and stimulation frequency (log2) (adapted from Evers et al., 2014).
Figure 3 Group data (N=8) showing the restorative action of SNS on anorectal EP amplitude.
C.
B.
A.
Custom made rodent lead (Medtronic Inc.)