Effects of transcutaneous tibial nerve stimulation on anorectal physiology in fecal incontinence: a double-blind placebo-controlled cross-over evaluation

Authors

  • G. Bouguen,

    Corresponding author
    1. Service des Maladie de l'Appareil Digestif, Centre Hospitalier Pontchaillou et Université de Rennes 1, Rennes, France
    2. INSERM U991, Université de Rennes 1, Rennes, France
    • Address for Correspondence

      Dr Guillaume Bouguen, Service des Maladies de l'Appareil Digestif, CHU Pontchaillou, 2 rue Henri le Guilloux, Rennes Cedex 35033, France.

      Tel: + 33 2 99 28 43 17; fax: + 33 2 99 28 41 89;

      e-mail: gbouguen@free.fr

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  • A. Ropert,

    1. Service des Explorations Fonctionnelles, Centre Hospitalier Pontchaillou et université de Rennes 1, Rennes, France
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  • F. Lainé,

    1. Unité d'investigation Clinique, Centre Hospitalier Pontchaillou et université de Rennes 1, Rennes, France
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  • P. Pequin,

    1. Service des Explorations Fonctionnelles, Centre Hospitalier Pontchaillou et université de Rennes 1, Rennes, France
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  • J. Morcet,

    1. Unité d'investigation Clinique, Centre Hospitalier Pontchaillou et université de Rennes 1, Rennes, France
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  • J.-F. Bretagne,

    1. Service des Maladie de l'Appareil Digestif, Centre Hospitalier Pontchaillou et Université de Rennes 1, Rennes, France
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  • L. Siproudhis

    1. Service des Maladie de l'Appareil Digestif, Centre Hospitalier Pontchaillou et Université de Rennes 1, Rennes, France
    2. INSERM U991, Université de Rennes 1, Rennes, France
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Abstract

Background

Transcutaneous electrical tibial nerve stimulation (TENS) is of growing interest for the treatment of fecal incontinence (FI), but its mechanism of action remains uninvestigated. We aimed to further assess the anorectal response to TENS in a dynamic model.

Methods

We performed a placebo-controlled, randomized, double-blinded crossover study in 19 patients suffering from FI to assess the effects of TENS on anorectal function. Anorectal physiology and perception were recorded through two sequences of rectal isobaric distension using an electronic barostat device to measure anal and rectal pressures, rectal volumes, and perception scores.

Key Results

Maximal rectal pressure and volume variation were affected by TENS, with higher mean maximal rectal pressure (5.33 and 4.06 mmHg in the active and sham TENS respectively, p < 0.0001) and lower volume variation (11.45 and 14.7 mL in the active and sham stimulation respectively, p < 0.05). Rectal compliance was not modified by active TENS. Pressure of the upper anal canal was significantly lower with raised isobaric distension in sequences assigned to active TENS.

Conclusions & Inferences

Acute TENS modified anorectal physiology by strengthening the myogenic response to distension rather than increasing muscle relaxation and related rectal compliance in patients with FI.

Key Messages

  • Mechanisms of action of transcutaneous electrical tibial nerve stimulation on anorectal function remain unknown.
  • Using a model of isobaric distension in a placebo-controlled, randomized, double-blinded crossover study design, we showed that transcutaneous electrical tibial nerve stimulation impact on rectal and pressure as well as rectal volume variation.
  • These findings suggest a strengthening of the anorectal myogenic response during transcutaneous electrical tibial nerve stimulation.
Abbreviations
FI

fecal incontinence

SNS

sacral nerve stimulation

TENS

transcutaneous electrical nerve stimulation

Introduction

Fecal incontinence (FI) is a frequent condition of diverse etiology leading to significant impairment of quality-of-life related to its devastating psychosocial implications.[1, 2] Multiple mechanisms may be involved in its pathophysiology such as stool habits, defecation disorders, abnormal rectal capacity or compliance, decreased anorectal sensation, and pelvic floor or anal sphincter dysfunction.[1]

By avoiding invasive surgical procedures, electrical stimulation has received increasing attention for patients with persistent FI despite conservative therapies (e.g. biofeedback, diet modification, laxatives or anti-diarrheal drugs). Sacral nerve stimulation (SNS) was demonstrated to drastically improve patients in both the short and long term. In patients that responded to a short period of test stimulation, SNS decreased FI episodes, ability to postpone defecation, and eventually improved quality of life.[3, 4] This technique remains relatively expensive, however, and requires a minimally invasive surgical procedure for neurostimulator implant that could result in some adverse events such as pain, infections, or paresthesias.

Sharing the common purpose of sacral nerve simulation, transcutaneous electrical tibial nerve stimulation (TENS) is of growing interest to treat FI by overcoming disadvantages of SNS. Based on traditional Chinese practices using acupuncture points over the posterior tibial nerves, TENS aims to indirectly modulate the sacral plexus by reflex pathways. The method applies a current via a transcutaneous, positive stick-on electrocardiograph-type electrode with foam backing placed over the posterior tibial nerve and a ground electrode placed over the same nerves ipsilaterally.[5] Transcutaneous electrical tibial nerve stimulation is a non-invasive technique that can suppress detrusor instability or hyperreflexia and consequently was approved to treat overactive bladder.[5-8]

Whether this approach impacts FI, and in particular the symptom of urgency, remains debated.[9-11] Of note, no study has been conducted to directly assess change in anorectal function following TENS and the mechanism of action of electrical stimulations remains incompletely understood. Sacral nerve stimulation treatment seems to result in a variety of physiological effects that involve sensorimotor rectal and anal responses to distension, bowel motility, and brain perception.[3, 12-14]

A better understanding of physiological targets of acute TENS would be helpful to define its rule in the management of FI. The aim of this study was therefore to investigate mechanisms involved in the anorectal response induced by TENS.

Methods

Study population

Nineteen patients naïve to TENS or SNS that suffered from FI were enrolled with at least one liquid and/or solid stool leakage per week and an incontinence score above 8.[15] At baseline, each patient underwent a standard questionnaire assessing their level of incontinence (Cleveland Clinic Florida—Fecal Incontinence score [CCF-FI]) quality of life scale (Gastrointestinal Quality of Life Index – Fecal Incontinence Quality of Life) and a physical examination. All patients experienced previous failure to conservative medical therapy including dietary counseling and retraining sessions. Patients were excluded if they were pregnant or had a recent delivery (less than 4 months prior), diabetes, stool impaction, high-grade rectal prolapse (apparent on straining), previous rectal surgery, congenital abnormality of the anus or rectum, or a pacemaker.

Study design

The study protocol was reviewed and approved by the committee for ethical research (registration number 2008-A00842-53, Comité de Protection des Personnes, University Hospital of Pontchaillou, Rennes, France), and all patients provided written informed consent before entering the study.

This was a placebo-controlled, randomized, double-blind crossover study that included two consecutive rectal isobaric distension sequences. Baseline visit and each sequence were separated from the next one by at least a 7-day washout period. During each sequence, active or sham TENS was applied to the patients in a randomized order.

Stimulation procedure

Stimulation was carried out using self-adhesive surface stimulation electrodes without an implanted needle electrode. The stimulator was a TENS Eco Program P3 (Schwa Medico France 68250 Rouffach France). Contact electrodes were placed on the patient's skin with electrode gel with the negative electrode behind the internal malleolus and the positive electrode 10 cm above the negative electrode. To maintain the double-blind design, the intensity level for stimulation was set during the baseline visit as the intensity immediately under the threshold determining electrical sensation. Stimulation frequency was then applied at 10 Hz and a pulse width of 200 ms in continuous mode. Patients were unable to use the TENS between the inclusion visit and the beginning of the first sequence and were also unable to use it between sequences. Nerve stimulation was applied before isobaric distension by an independent investigator according to the randomization and was hidden to the operating investigator.

Rectal isobaric distension

Distension procedures were performed with a highly compliant polyethylene bag placed within the rectum and connected to the electronic barostat (ABS, Saint Die, France) as previously described.[16, 17] Briefly, once the bag was introduced into the rectum, the barostat maintained a constant preselected pressure within the rectal bag by an electronic feedback mechanism. When the rectum accommodated or relaxed completely, air was injected and bag volume increased. The compliant polyethylene bag had a maximal capacity of 600–650 mL. Phasic distensions were performed by rapid inflation of the bag to successive predetermined ascending levels of pressure (increments of 2 mmHg until a level of 16 mmHg, then by 4 mmHg until the end of the procedure). Pressure at each level was maintained for 60 s and separated from the next level by a 60 s waiting period at 0 mmHg.

Anal manometry

Anal manometry was performed at baseline and before each sequence using a 4-lumen, water-perfused catheter (R3B and PIP4-4; Mui Scientific, Mississauga, ON, Canada) to record mean maximal resting pressures at both the upper and lower portions of the anal canal (Computerized Motility System; Sandhill, Highlands Ranch, CO, USA). Mean squeeze pressure at the lower anal part was obtained during a 30 s long squeeze effort. Rectal perception thresholds were recorded using isovolumetric distension with balloon air inflation. During isobaric distension of the rectum, rectal and anal pressures were recorded continuously.

Experimental protocol

A 200 mL water enema was administered 2 h before the onset of the procedure. Each subject was placed in the left lateral position, in a quiet environment. The bag and the catheter for manometry were lubricated and inserted into the rectum 30 min before the procedure. A resting state of 20 min was used to obtain accommodation of the anorectal area to the device. Baseline anal pressures were recorded. Active or sham TENS was then applied in a random order: both patient and investigator were blinded to the nature of the stimulation during the phasic distension which began 5 min after starting the TENS. The distension was stopped when the pain or the defecation score was equal to or above 4 for one of them on a 5-point likert scale (see below), or a barostat pressure above 60 mmHg.

Study parameters and outcomes measures

In response to the rectal distension protocol, the following parameters were monitored or derived from the recorded data.

Anal pressures in the upper and lower anal canal

Conventionally, the upper part is thought to reflect the manometric activity of the internal anal sphincter and the lower part the activity of the external anal sphincter. At each pressure step, the anal pressure was expressed as the residual and maximal pressure recorded at the level investigated.

Maximum rectal pressure

Rectal pressure was recorded by the manometric device during each step of distension in order to analyze the occurrence of rectal contractions.

Maximum volume of the rectum

Maximum rectal volume was recorded at the end of each step of preselected pressure.

Volume related to compliance

This was defined by a volume variation in response to an ascending pressure. It represents the difference between the resting state (0 mL) and the measured volume when the preselected pressure was just reached. Because this was a volume variation over the variation of two levels of pressure, this phase may reflect rectal compliance.[16, 17]

Volume related to tone

This was a volume variation in response to a stabilized preselected pressure at the end of the distension step; it describes rectal tone in this phasic isobaric distension model.[16, 17]

Sensation intensity

Pain score was assessed at each pressure step (when rectal pressure was just stabilized) using a 5-point likert scale ranging from no sensation to intolerable pain. Similarly, need to defecation during isobaric rectal distension was assessed using a 5-point likert scale ranging from no perception of defecation to urgent need to defecate.

Statistical analysis

Data were analyzed using SAS software V9.2 (SAS Institute, Cary, NC, USA). Reported values are mean values (SD). All patients were included in the analysis. Changes in the levels of distending pressure and treatment/pressure interaction were analyzed using four-way anova (subject, pressure, treatment, sequence order or treatment order). p < 0.05 was considered to be statistically significant. When treatment effects were significant, Student's t-tests were used for pairwise comparisons between mean values computed throughout all levels of distending pressure (in contrast to the analysis following the mixed model of repeated measures anova).

Results

Characteristics of the patients

One patient withdrew consent after the first sequence of isobaric distension. Demographic and baseline characteristics of the 19 patients are listed in Table 1. All women had a history of pregnancy with vaginal delivery. Fecal incontinence failed to improve after biofeedback alone or with adjunctive treatments for stools habits for all patients. Six patients had prior anal surgery that included sphincter repair for one patient, Milligan-Morgan hemorrhoidectomy for four patients and hemorrhoid band ligation for one patient. Endoanal ultrasound performed in 18 out of 19 patients showed sphincter defects for four patients, including two patients with previous anal surgery. Abdominal surgery consisted of segmental colectomy proximal to the rectum for two patients, hysterectomy for six patients, and cholecystectomy or appendectomy for the others. The mean CCF-FI score corresponded to moderate to severe incontinence among the population study impacting quality of life. A total of 15 patients had incontinence with urgency. Leakage was associated with urgency for 14 out of the 15 patients. The four remaining patients experienced passive incontinence. There were no differences across groups receiving stimulation or sham TENS during the first sequence and consecutively for the second sequence (Table 1). Baseline anal physiology is reported in Table 2.

Table 1. Baseline characteristics
VariableOverall cohort (N = 19)Active tens 1st sequence (N = 10)Sham tens 1st sequence (N = 9)p acitive/sham
  1. SEM, standard error of the mean; CCF-FI, Cleveland Clinic Florida—Fecal Incontinence score; TENS, Transcutaneous Electrical Nerve Stimulation; GIQLI, Gastrointestinal Quality of Life Index.

Female gender – n (%)18 (94.7)9 (90.0)9 (100.0)1.00
Smoking – n (%)1 (5.3)0 (0.0)1 (11.0)0.47
Age – mean (SD)64.7 (9.5)63.5 (10.0)66.1 (9.3)0.57
Prior surgery – n (%)
Abdominal surgery13 (68.4)7 (70.0)6 (33.3)1.00
Colonic resection2 (10.5)1 (10.0)1 (33.3)1.00
Anal surgery6 (31.6)2 (20.0)4 (44.4)0.35
Incontinence items – n (%)
Solid leakage12 (63.2)6 (60.0)6 (66.7)1.00
Liquid leakage19 (100.0)10 (100.0)9 (100.0)1.00
Urgency without leakage12 (63.2)8 (60.0)4 (44.4)0.17
Urgency with leakage14 (73.7)8 (60.0)6 (66.7)0.63
Urinary Incontinence11 (57.9)6 (60.0)4 (44.4)1.00
Dyschezia8 (42.0)4 (40.0)4 (44.4)1.00
CCF-FI13.0 (2.8)13.0 (3.2)12.9 (2.4)0.93
GIQLI87.1 (32.8)86.7 (17.1)87.4 (45.8)0.96
Prior treatments– n (%)
Biofeedback19 (100.0)10 (100.0)9 (100.0)1.00
Stool softener and bulking agents11 (57.9)5 (50.0)6 (66.7)0.65
Anti-diarrheal drugs4 (21.1)1 (10.0)3 (33.3)0.30
Table 2. Baseline anal physiology before stimulation
VariableMean (SD); range
  1. RAIR, recto-anal inhibitory reflex; SD, standard deviation.

Functional anal canal length (mmHg)18.16 (6.31); 10–30
Resting pressure (upper part; mmHg)43.32 (20.11); 10–82
Resting pressure (lower part; mmHg)41.89 (21.49); 10–92
Squeeze pressure (mmHg)23.37 (17.49); 0–55
Threshold volume RAIR (mmHg)21.58 (6.38); 10–40
Straining pressure (mmHg)28.37 (10.75); 10–68

After the study period, all patients were treated with TENS and followed according to the standard of care. The mean duration of active TENS was 5 months (4.18) and 10 out of 19 patients (52.6%) reported some improvement of fecal incontinence.

Pressure effect and TENS stimulation-pressure interaction

A significant pressure effect was observed for each investigated variable, except for the mean pressure in the upper (p = 0.07) and lower portions (p = 0.7) of anal canal. Initial and maximal rectal volumes, maximal rectal pressure, defecation sensation, and pain significantly increased (p = 0.0001 for the five variables) whereas residual pressure at the upper anal canal (p = 0.0001) significantly decreased with increasing rectal distension. There was no significant TENS stimulation-pressure interaction for any variable.

Isobaric distension and defecation score

Both pain and defecation scores rose with increasing levels of rectal distension. Distension was discontinued up to maximum defecation score. The mean level of pressure step reached by barostat distension was 26 mmHg (6.4; range 16–40) in both sequences and did not differ according to the stimulation procedure (mean distension step: 25.7(6.3) mmHg for active TENS vs 26.3(6.7) mmHg for sham procedure, p = 0.55). Mean pain score at the discontinuation step did not vary according to the stimulation procedure (mean pain score: 1.11(1.74) mmHg for active TENS vs 1.08(1.71) mmHg for sham procedure, p = 0.38).

Effects of TENS on rectal volume, tone, and compliance

As expected, increasing isobaric distention steps were highly correlated with rectal pressure (κ = 0.79, p < 0.0001), volume related to compliance (κ = 0.67, p < 0.0001), and maximal rectal volume (κ = 0.67, p < 0.0001). Figure 1 shows the measured and calculated variables of the rectal wall according to each step of isobaric rectal distension. Maximal rectal pressures were higher during TENS (5.33 (6.15) mmHg) as compared to sham procedure (4.06 (5.08) mmHg respectively, p < 0.0001; Fig. 1A). Variation of rectal volumes at a stabilized pressure (which is related to the rectal tone) significantly differed according to the TENS procedure. The mean change was 11.45 mL (15.3) in the active TENS and 14.7 (19.2) in the sham stimulation (p < 0.05). The mean rectal compliance (2.86 (3.52) mmHg/mL) did not change according to the TENS stimulation.

Figure 1.

Maximal rectal pressures and volume related to tone recorded for each step of isobaric rectal distension. There was a significant pressure effect of transcutaneous electrical nerve stimulation with higher maximal rectal pressure (p < 0.0001). Variation of rectal volumes at stabilized pressure were significantly lower in active SHAM sequences (p < 0.05). Mean and SEM are represented for each step of isobaric distension.

Anal canal pressures

As compared to the sham procedure, TENS stimulation did not significantly modify the following anal pressures to rectal distension: mean upper anal canal pressure (42.5 (24.4) mmHg; stimulation effect: p = 0.24); mean lower anal canal pressure (37(17.8) mmHg; stimulation effect: p = 0.69); mean residual pressure (29(23.8) mmHg; stimulation effect: p = 0.97). Figure 2 shows the recorded maximal pressures in the anal canal during rectal distention. A significant stimulation effect (p = 0.0005) was observed: it was overall significantly lower in the active TENS sequence 26.87(17.56) than in the sham TENS sequence 29.75(18.24) mmHg (p = 0.0005).

Figure 2.

Maximal anal pressure for each step of isobaric rectal distension. There was a significant decrease of maximal anal pressure after active transcutaneous electrical nerve stimulation (p = 0.0005). Mean and SEM are represented for each step of isobaric distension.

Discussion

This is the first study offering insight into the anorectal changes induced by transcutaneous tibial nerve electrical stimulation. The impact of TENS on rectal wall led to decrease rectal adaptation and maximum anal pressure in a model of isobaric distension. These conclusions contrast with the observed effect in overactive bladder, but are consistent with the fact that this method also acts on bladder retention.

The mechanism by which TENS acts on FI remains unknown. TENS may alter the somato-visceral pathway through the sacral plexus, analogous to SNS.[18] Data suggest a mixed mechanism of action on anal muscle and rectal sensory function and central neurologic effects.[19] In fact, SNS and TENS have been shown to increase rectal compliance.[20] However, our results did not support a similar effect on rectal wall, without significant effect on rectal compliance. Using a similar assessment based on a validated procedure, Roman et al. found no difference of rectal compliance after chronic SNS (3 months) assessed by the same sensitive method.[21]

Clinical efficacy of TENS remains highly debated. Several prospective open-label and retrospective studies and a randomized controlled trial on a small number of patient showed promising results with a profound improvement for up to 80% of patients suffering from FI.[11, 22] However, a recent multicenter randomized, double-blind, sham-controlled trial, including 144 patients failed to demonstrate any benefits of TENS over sham stimulation in the number of incontinence and urgency episodes (primary endpoint), whereas the reduction in FI episodes per week was significantly higher in the active group with a trend toward lower CCF-FI scores at 3 months.[9] Both in this trial and in our study, stimulation intensity was determined immediately under the threshold of electrical sensation to maintain the blind design. Although a suprasensory rather than a subsensory SNS stimulation have been linked to clinical outcomes, the level of stimulation has not been assessed for TENS and our results support that objective effects occur even with subsensory stimulation do not determine whether the effects would be greater with higher level of stimulation.[23] We previously described a discrepancy between variation of symptomatic scores and the clinically relevant benefit of TENS perceived by patients. Two-third of patients had decided by their own initiative to pursue the treatment, whereas CCF-FI was improved only in 23% of patients.[10] These results demonstrated that TENS enhanced quality-of-life regardless of the improvement of continence. Although some improvements were reported by half of patients after study period, the current study was performed to assess physiological changes induced by a single TENS stimulation and was not powered to assess clinical outcomes that would ultimately insure the association between such changes and outcomes of fecal incontinence. We did not find any difference in defecation score with or without stimulation in these single stimulations inefficient to modify the complex network of spinal and supraspinal response involved after neurostimulation.

Interestingly, we found a raised rectal maximal pressure and accordingly lower rectal volume variation after active stimulation related to higher isobaric distension. These results could explain the myogenic response and trophic effect on the rectal muscle led by increasing neurotransmission activity during active TENS. Incontinence may be improved by TENS by the way of a better reinforcement of the rectal wall properties and rectal emptying. Similar findings and conclusions were observed for a similar treatment approach with dorsal genital nerve stimulation in subjects with spinal cord injury.[24] Worsoe et al. found that acute stimulation in these subjects results in a significant smaller rectal pressure/rectal cross-sectional area (assessed by impedance planimetry) relation during rectal distensions, meaning a reduced rectal compliance, and an increase of rectal motor activity.[24] These results are consistent with a recent prospective European study showing a decrease in time spent toileting, straining, and perception of incomplete evacuation after SNS.[25] Usually feces remain in the rectum in healthy subjects after defecation without persistent urge to defecate, whereas stools are mostly retracted to the left side of the colon that is potentiated during SNS.[25-27] In either way by raising retrograde stools transport in association with increased colonic storage or by improving defecation, SNS may result in better rectal emptying by increasing rectal motor activity. Similarly, TENS acts on both bladder over-activity and retention suggesting a mixed effect. During bladder retention, SNS and electro-acupuncture increased detrusor pressure and contractibility, enhanced sphincter relaxation, and decreased bladder capacity and residual urine that led to improve voiding function. Taken together it emphasized paradoxical effects of TENS on FI.[28-30] Improvement in anorectal function by TENS could lead to achieve a better rectal emptying by improving the anal sampling reflex, rectal strength, low anal pressure, and control avoiding further incontinence episode. Increasing rectal volumes usually involves an amplification of the recto anal inhibitory reflex and a decrease in resting pressure of the anal canal. In the present study using a stepwise pressure distension, a biphasic response of anal pressure was observed in the sham but not in the TENS group. In fact, the mean anal pressure primarily decreases and secondarily remains stable or increases with higher steps of rectal distension. This has been reported in previous works using a similar methodology in healthy subjects.[31] By contrast, TENS group experienced a stepwise relaxation of the anal sphincter. This effect may be related to non-cholinergic pathways as cholinergic agents modify anal pressures independently to the level of rectal distension.[31] Finally, a previous work experienced that incontinent patients with hypersensitive rectum significantly increased maximal rectal pressure and decreased anal pressure to stepwise distension as compared to several control groups.[32] One hypothesis is that acute TENS may modulate rectal and anal tone through a neurological central pathway.

Collectively, our results underlined paradoxical but objective effects of TENS on anorectal function during FI that had never been reported. The absence of rectal compliance change may highlight the low objective benefit observed in clinical studies. Outcome of rectal tone after TENS suggests another way to explain patient satisfaction after stimulation that needs further investigation. Finally, this therapeutic option needs to be tested in patients suffering from constipation, due to the observed effect on both rectal tone and in patients suffering from bladder retention.

Funding

This work was funded by a research grant from the French Society of Colo-Proctology.

Conflicts of Interest

GB has received lecture fees from AbbVie, Ferring, and MSD Pharma. LS has received consulting fees from AbbVie and lecture fees from AbbVie MSD. J-FB has received lecture fees from Abbvie. AR, FL, JM declare no competing interest.

Author Contribution

GB, FL, AR, and LS study design; GB, LS, AR interpretation and analysis of data, editing of the manuscript; AR, LS, GB data collection; JM statistical analysis; all authors reviewed the paper and approved the final submitted draft.