ORIGINAL CONTRIBUTION

Electrical Stimulation of Anal Sphincter or

Pudendal Nerve Improves Anal Sphincter Pressure
Margot S. Damaser, Ph.D.1,2,3 • Levilester Salcedo, M.D.1 • Guangjian Wang, Ph.D.5
Paul Zaszczurynski, B.S.3 • Michelle A. Cruz, B.S.1 • Robert S. Butler, M.S.6
Hai-Hong Jiang, Ph.D.1 • Massarat Zutshi, M.D.4
1 Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio
2 Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio
3 Advanced Platform Technology Center, Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio
4 Department of Colorectal Surgery, Cleveland Clinic, Cleveland, Ohio
5 American Medical Systems Inc., Minnetonka, Minnesota
6 Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio

OBJECTIVE: Stimulation of the pudendal nerve or
the anal sphincter could provide therapeutic options
for fecal incontinence with little involvement of other
organs. The goal of this project was to assess the effects
of pudendal nerve and anal sphincter stimulation on
bladder and anal pressures.
DESIGN: Ten virgin female Sprague Dawley rats
were randomly allocated to control (n = 2), perianal
stimulation (n = 4), and pudendal nerve stimulation
(n = 4) groups. A monopolar electrode was hooked to
the pudendal nerve or placed on the anal sphincter.
A balloon catheter was inserted into the anus to measure
anal pressure, and a catheter was inserted into the
bladder via the urethra to measure bladder pressure.
Bladder and anal pressures were measured with different
electrical stimulation parameters and different timing
of electrical stimulation relative to spontaneous anal
nerve at stimulation values of 1 mA or 2 mA. No increase
in anal pressure was observed for lower current values.
Bladder pressure increased at high current during
anal sphincter stimulation, but not as much as during
pudendal nerve stimulation. Increased bladder pressure
during anal sphincter stimulation was due to contraction
of the abdominal muscles.
CONCLUSION: Electrical stimulation caused an increase
in anal pressures with bladder involvement only at
high current. These initial results suggest that electrical
stimulation can increase anal sphincter pressure,
enhancing continence control.
KEY WORDS: Electrical stimulation; Anal sphincter;
Bladder; Pudendal nerve; Pressure; Neuromodulation; Rat.

sphincter contractions.
RESULTS: Increasing stimulation current had the most
dramatic effect on both anal and bladder pressures. An
immediate increase in anal pressure was observed when
stimulating either the anal sphincter or the pudendal
Funding/Support: This research was supported in part by American
Medical Systems, The Cleveland Clinic Foundation, and the Rehabilita-
tion Research & Development Service of the Department of Veterans
Affairs.
Financial Disclosure: Dr Damaser acted as a consultant to American
Medical Systems in 2008 when this work was performed.
Correspondence: Massarat Zutshi, M.D., Cleveland Clinic Foundation,
9500 Euclid Ave, A30, Cleveland, OH 44195. E-mail: zutshim@ccf.org
Dis Colon Rectum 2012; 55: 1284–1294
DOI: 10.1097/DCR.0b013e31826ae2f8
© The ASCRS 2012
1284
F
ecal incontinence is a debilitating condition that
often occurs in conjunction with urinary inconti-
nence.1,2 It affects both men and women, but it is
more common among women because of childbirth inju-
ry resulting from an episiotomy, stretch injury to the anal
sphincter, and/or pudendal nerve injury.3,4
Neuromodulation has been used to stimulate the
periurethral musculature and anal sphincter via the sacral
nerve routes as they emerge from the spinal canal.5,6 Sacral
nerve stimulation is approved by the US Food and Drug
Administration for urinary incontinence6,7 and recently for
fecal incontinence.8–11 A small study in urinary incontinence
compared sacral and pudendal stimulation and found that
patients preferred pudendal stimulation.12 Additionally, a
recent study demonstrated that a small number of patients
with fecal incontinence in whom sacral nerve stimulation
failed improved with pudendal nerve stimulation, although
this must be studied with a larger sample size.13
DISEASES OF THE COLON & RECTUM VOLUME 55: 12 (2012)
DISEASES OF THE COLON & RECTUM VOLUME 55: 12 (2012)
Stimulation of the pudendal nerve or of the anal sphinc-
ter for fecal incontinence has been recently investigated.13
Pudendal nerve stimulation could provide anal sphincter
contraction without involvement of other organ systems.
­Either stimulation type could potentially provide an efficient
method of increasing anal sphincter pressure. The objective
of this study was to investigate the effects on anal sphinc-
ter and bladder pressures after electrical stimulation of the
­pudendal nerve or the anal sphincter in female rats.
METHODS
The experimental protocol was approved by the Institu-
tional Animal Care and Use Committee of the Cleveland
Clinic. Ten virgin Sprague Dawley rats (240–260 g) were
randomly allocated into 3 groups: control (n = 2), anal
sphincter stimulation (n = 4), and pudendal nerve stimula-
tion (n = 4). Anal sphincter function was assessed according
to previously described methods.12 Under intraperitoneal
anesthesia with ketamine (100 mg/kg) and xylazine (10
mg/kg), a small balloon (Kent Scientific, Torrington, CT;
size 4, diameter 4 mm) attached to a water-filled catheter
(PE-90 tubing, inside diameter 86 mm, outside diameter
1.27 mm) was pressurized and shallowly inserted into the
rat’s rectum. Balloon pressure was referenced to zero at
the level of the anus. Anal pressures were then measured
continuously throughout the experiment via the catheter
with the use of a pressure transducer (Grass Astromed,
PT300, Warwick, RI) connected to an amplifier (Astromed
Inc, model P-122/ and digital data recording system (Dash
8x, Astromed Inc) as in our previous study.12 Anal pres-
sure recordings were analyzed with the use of Astroview X
software (Astromed Inc, version 1.3) for differences in am-
plitude before and after electrical stimulation.
Bladder pressure was recorded simultaneously with
anal sphincter pressures via a saline-filled catheter (PE-50
tubing, inside diameter 0.58 mm, outside diameter 0.965
mm) transurethrally.14 The bladder was filled at 5 mL/h
with room-temperature saline via the urethral catheter.
Bladder pressure recordings were similarly analyzed for
differences in amplitude and characteristic shape before
and after electrical stimulation. Control animals were
anesthetized for the same time as experimental animals
but underwent no stimulation.
Direct electrical stimulation of the anal sphincter
was performed by using a monophasic signal on 4 ani-
mals via platinum needle electrodes (Grass, Warwick, RI;
12 mm, 30 gauge) placed shallowly into the anal sphinc-
ter muscle bilaterally without disturbing the abdomi-
nal musculature. Electrical stimulation of the pudendal
nerve was performed on 4 animals with the use of bent
platinum electrodes (0.8 mm distance between poles, 0.25
mm ­diameter, PB AD08100; FHC, Bowdoin, ME) hooked
­directly on the nerve as it traverses the ischiorectal fossa,
distal to the branching of the pudendal nerve at the sciatic
1285
notch and proximal to the location where the pudendal
nerve branches into many fine nerves. The anode and
cathode for each pair were placed in close proximity. To
obtain access to the pudendal nerve, the ischiorectal fossa
was dissected bilaterally and accessed from the ventral
side after opening the abdominal muscle and pubic sym-
physis (Fig 1).14 In our preliminary studies, we found little
to no difference in the response to biphasic and mono-
phasic stimulation. Therefore, for pudendal nerve stimu-
lation, we used bilateral monophasic stimulation.
Three experiments were performed on each animal.
The first investigated the effect of varying current, pulse
duration, frequency, and duration of stimulation on blad-
der and anal pressures during baseline pressure recordings
between spontaneous anal sphincter contractions. Four
current levels (0.25, 0.5, 1.0, and 2.0 mA), 3 stimulus du-
rations (1.0, 5.0, and 10.0 seconds), 3 frequencies (20, 30,
and 40 Hz), and 3 pulse durations (50, 75, and 100 μs)
were investigated with both anal sphincter and pudendal
nerve stimulation.
Testing of all possible combinations of these vari-
ables would have required 108 stimulations in each ani-
mal; which could fatigue the anal sphincter and reduce the
reliability of the results. Therefore, D-optimal design15,16
construction was used to identify 12 experimental com-
binations that would permit an investigation of the linear
and curvilinear effects of changes in current, duration, fre-
quency, and pulse duration. These 12 stimulations were
performed twice in randomized order in each animal.
A second experiment was performed in the same
animals to investigate the effects of timing of stimulation
relative to spontaneous anal sphincter contractions. Elec­
trical stimulation was randomly initiated at the beginning,
middle, and end of a spontaneous contraction and be­
tween spontaneous contractions (Fig. 2). The timing of
stimulation was obtained from anal pressure recordings in
unstimulated animals and experience from our previous
studies,12,17 which showed spontaneous anal contractions
that were very consistent. Stimulation was performed with
the stimulating needle in place while viewing the anal
contractions on the recorder in real time.
The stimulation parameters were held constant dur-
ing this experiment at 2 mA amplitude, 10 seconds dura-
tion, 30 Hz frequency, and 100 μs pulse duration.
To determine whether abdominal muscle contrac-
tion from anal sphincter stimulation contributed to the
rise in bladder pressure, electrical stimulation of the anal
sphincter was performed before and after abdominal mus-
cle transection which reduces intraperitoneal pressure to
zero. A high current value (4 mA) that would produce a
bladder pressure response to stimulation was used in this
experiment with 20 Hz, 100 µs pulse duration, and 5 sec-
onds duration stimulation.
To determine whether the effects of pudendal nerve
stimulation were due to signal transmission via the
1286
FIGURE 1. Illustration of the anatomy of the pudendal nerve in a rat. A, Sacral plexus containing pudendal nerve. * = the location of elec­
trodes hooking the pudendal canal which contains both sensory and motor branches of the pudendal nerve. B, Ventral view of the stimulation
location for the pudendal nerve in a female rat (ischiorectal fossa opened after separating pubic symphysis). C, The boxed area in B is enlarged
to demonstrate the pudendal canal.
pudendal nerve or to spread of the electrical signal via
surrounding tissues, the same stimulation settings were
used as above 3 times before and 3 times after bilateral
pudendal nerve transection proximal to the stimulating
electrode. The pudendal nerve was then transected dis-
tal to the electrode, leaving a small isolated piece of pu-
dendal nerve sitting across the bipolar electrode, which
was stimulated, and pressures were recorded.
The changes in anal and bladder baseline and contrac-
tion pressures with stimulation were calculated. Because
anal pressure contained spontaneous contractions, the
maximum, minimum, and mean changes in pressure were
calculated for anal sphincter pressure during spontaneous
contractions. The average value of each variable at each
setting for each animal was obtained and used to create a
group mean that was used for statistical comparisons.
To determine the effect of varying electrical stim­
ulation parameters, each outcome was analyzed by using
linear regression, and the results were summarized in the
form of a regression equation relating significant variables
to the measured response, with p < 0.05 indicating a
statistically significant difference. To determine the effect
of timing of stimulation, each outcome was analyzed by
using a 1-way ANOVA, followed by a Tukey-Kramer post
hoc pairwise means comparison, with p < 0.05 indicating
a statistically significant difference. Change in anal
sphincter or bladder pressure resulting from changing
each stimulation variable is expressed as mean ± SEM of
data from 4 animals.
DAMASER ET AL: ELECTRICAL STIMULATION: ANAL SPHINCTER
RESULTS
There was no significant change in anal sphincter or bladder
pressure in control animals while they were anesthetized.
Effect of Varying Stimulation Parameters
Increasing the current had the most dramatic effect on both
anal and bladder pressures of all stimulation variables test-
ed. Anal pressure increased significantly during 1- or 2-mA
stimulation of either the anal sphincter or pudendal nerve.
In contrast, there was little to no increase in anal pressure
observed during 0.5- or 0.25-mA stimulation. Increased
current significantly increased the maximum (2.9 ± 0.4 cm
H2O, p < 0.001), minimum (1.0 ± 0.5 cm H2O, p = 0.046),
and average (2.6 ± 0.3 cm H2O, p < 0.001) change in anal
sphincter pressure with both anal sphincter and pudendal
nerve stimulation (Fig. 3).
Increasing frequency significantly decreased the maxi-
mum change in anal sphincter pressure (0.8 ± 0.4 cm H2O,
p = 0.047) during anal sphincter stimulation only (Fig. 3A).
Anal sphincter baseline pressure also increased significant-
ly with increased current (0.7 ± 0.3 cm H2O, p = 0.04) and
changed nonlinearly with increased frequency (–1.3 ± 0.6
cm H2O, p = 0.04; Figs. 3C and D). The maximum (–1.0 ±
0.4 cm H2O, p = 0.005), minimum (0.7 ± 0.3 cm H2O, p =
0.008), and average (1.8 ± 0.3 cm H2O, p < 0.0001) change
in anal sphincter baseline pressure due to anal sphincter
stimulation decreased significantly with increases in pulse
duration (Fig. 3C). The minimum change in anal sphinc-
ter baseline pressure due to nerve stimulation decreased
DISEASES OF THE COLON & RECTUM VOLUME 55: 12 (2012)
Pressure
80
70
60
50
Middle of
40 spontaneous
contraction
30
Rest period Beginning of End of
20 between 2 spontaneous spontaneous
spontaneous contraction contraction
contractions
10
0 10 20 30 40 50
Time (sec)
FIGURE 2. Example of a spontaneous anal sphincter (upper
trace) and simultaneous bladder (lower trace) pressure recording
demonstrating the experimental design to investigate the effects of
varying timing of electrical stimulation with respect to spontaneous
anal sphincter contractions. Timing choices are at the beginning,
middle, or end of a spontaneous contraction or during the rest
period between 2 spontaneous contractions.
(4.4 ± 0.1 cm H2O, p < 0.001) with increasing duration of
stimulation, whereas the average change in anal sphincter
baseline pressure due to nerve stimulation decreased with
increases in current.
Because stimulation was timed to occur between anal
sphincter contractions, increases in bladder pressure di-
rectly related to stimulation were difficult to demonstrate,
because spontaneous bladder contractions were not con-
sistently timed with stimulation. Nonetheless, maximal
change in bladder pressure due to either anal sphincter or
pudendal nerve stimulation was significantly increased by
increases in both current (9.7 ± 3.4 cm H2O, p = 0.001) and
pulse duration (5.5 ± 1.2 cm H2O, p < 0.001; Figs. 3E and F).
Average change in bladder pressure due to pudendal nerve
stimulation was also significantly increased by increases in
current (3.8 ± 0.9 cm H2O, p = 0.001), pulse duration (1.9
± 0.7 cm H2O, p = 0.01), and frequency. There were no sig-
nificant effects on baseline bladder pressure due to either
anal sphincter or pudendal nerve stimulation.
Effect of Varying Timing of Stimulation
A noticeable increase in anal pressure was observed with
all stimulations regardless of timing, although this could
be difficult to discern when stimulation was performed
during a spontaneous anal sphincter contraction (Fig. 4).
Bladder pressure was also relatively responsive to electri-
cal stimulation; however, the changes in bladder pressure
were not significantly dependent on the timing of stimula-
tion relative to anal sphincter contraction with either anal
1287
sphincter or pudendal nerve stimulation, demonstrat-
ing the independence of spontaneous bladder and anal
sphincter contractions (Fig. 4).
The increase in anal sphincter pressure was significant-
ly greater if anal sphincter stimulation was initiated at the
beginning of a spontaneous anal sphincter contraction than
if it was initiated at the end of a spontaneous anal sphincter
contraction (Fig. 5). The minimal increase in anal sphincter
pressure was significantly greater if anal sphincter stimu-
lation was initiated in the middle of a spontaneous anal
sphincter contraction (31.8 ± 3.7 cm H2O) than if it was
initiated at the end of a spontaneous anal sphincter contrac-
tion (20.5 ± 3.7 cm H2O, p = 0.003; Fig. 5). Anal sphincter
stimulation initiated at the end of a spontaneous contrac-
tion caused on average a small decrease in minimum anal
sphincter pressure relative to baseline values. This was not
typical of anal sphincter stimulation initiated at any other
time relative to spontaneous anal sphincter contractions.
Maximal, minimal, and average baseline anal sphincter
pressure increased significantly with anal sphincter stimu-
lation at the beginning of a spontaneous anal sphincter con-
traction in comparison with stimulation at the middle or
end of a spontaneous anal sphincter contraction (Fig. 5).
Both maximal and average increase in anal sphincter
pressure were significantly greater if the pudendal nerve was
stimulated at the beginning of a spontaneous anal sphinc-
ter contraction (maximum, 24.1 ± 2.8 cm H2O; average,
20.2 ± 3.1 cm H2O) than if it was stimulated at the end of a
spontaneous anal sphincter contraction (maximum, 16.3 ±
2.8 cm H2O; average, 14.48 ± 3.1 cm H2O; Fig. 6). Similarly,
nerve stimulation initiated at the end of a spontaneous anal
sphincter contraction resulted in a small drop in anal sphinc-
ter pressure relative to baseline values. Average baseline anal
sphincter pressure significantly increased if stimulation was
initiated at the beginning (10.1 ± 3.0 cm H2O) of a sponta-
neous anal sphincter contraction in comparison with stimu-
lation initiated at either the middle or end (20.7 ± 3.0 cm
H20; p = 0.001; 16.0 ± 3.0 cm H2O, p = 0.03). Both maximal
(20.2 ± 3.1 cm H2O) and minimal (12.8 ± 2.8 cm H2O) anal
sphincter pressure significantly decreased if stimulation was
initiated at the end of a spontaneous anal sphincter contrac-
tion in comparison with stimulation initiated at the begin-
ning of a spontaneous contraction (p < 0.05; Fig. 6).
Effect of Muscle and Nerve Transection
At the end of the anal sphincter stimulation studies, the
anal sphincter was stimulated before and after the ab-
dominal musculature was cut. Muscle transection resulted
in a significant decrease (to zero) of the bladder pressure
response to anal sphincter stimulation, indicating that the
increase in bladder pressure from anal sphincter stimula-
tion was due to increased pressure on the bladder from
abdominal muscle contraction (Figs. 7A and B).
The pudendal nerve was stimulated before and after
transecting the pudendal nerve proximal and then distal to
1288 DAMASER ET AL: ELECTRICAL STIMULATION: ANAL SPHINCTER

FIGURE 3. Phase plots showing the effect of change of current, pulse duration, and frequency on anal contraction pressures. A, Increased anal
sphincter contraction pressure with anal sphincter stimulation occurs with increase in both current and frequency. B, Increase in anal sphincter
contraction pressure with pudendal nerve stimulation occurs with increase in current alone. Increase in anal sphincter baseline pressure with
anal sphincter stimulation occurs with increase in current as well as pulse duration and frequency. The data shown are at frequency of 20 Hz
(C) and 40 Hz (D). E, Increase in bladder pressure with anal sphincter stimulation occurs with increase in current and pulse duration. F, Increase
in bladder pressure with pudendal nerve stimulation occurs with increase in current and pulse duration.
DISEASES OF THE COLON & RECTUM VOLUME 55: 12 (2012) 1289

A B
Pressure (cm H2O) Pressure (cm H2O)
60 Bladder pressure
45
Bladder pressure Anal sphincter pressure
Anal sphincter pressure
50 40

35
40
30
30
25
20
20

10
15

0 10 20 30 40 50 60 0 10 20 30 40 50 60
Times (seconds) Times (seconds)

C D
Pressure (cm H2O) Pressure (cm H2O)
24 30
22
20 25
18
16 20
14
12 15
10
8 10
6

0 10 20 30 40 50 60 70 0 10 20 30 40 50 60 70
Times (seconds) Times (seconds)

FIGURE 4. Example of the anal sphincter (dotted line) and bladder (solid line) pressure before, during, and after electrical stimulation of the
anal sphincter (A, B) and pudendal nerve (C, D) during the experiment to assess the effect of varying the timing of stimulation. Stimulation was
performed between (A), at the end (B), at the beginning (C), and in the middle (D) of a spontaneous anal sphincter contraction. Stimulation
parameters consisted of 2 mA, 30 Hz, and 100 μs pulse duration and were of 10 seconds duration. The thick horizontal bar indicates timing and
duration of stimulation. Stimulation settings for each example are given above the graph. ma = current (mA); pps = frequency (Hz); s = duration
(seconds); us = pulse duration (µsec).

the site of stimulation. Nerve transection proximal to the
stimulating electrode did not alter bladder and anal pressure
responses to pudendal nerve stimulation. Nerve transection
distal to the stimulating electrode resulted in a significant
decrease (to zero) of the anal sphincter pressure response to
nerve stimulation (Figs. 7C and D), indicating that the effects
of pudendal nerve stimulation were via transmission of the
signal along the motor branch of the pudendal nerve rather
than by reflex action or spread of signal to nearby tissues.
DISCUSSION
Incontinence to solid and liquid stool are the result of anal
dysfunction, 18–20 which, in women, can often be attributed
to direct anal sphincter laceration and repeat stretching of
the pudendal nerve during childbirth.21 The current array
of therapeutic options includes conservative treatment and
surgical options.22 However, long-term results after sphinc-
ter repair are not satisfactory23,24 whereas sacral nerve stim-
ulation has gained acceptance in selected patients.9–11,25 We
investigated electrical stimulation as an alternative treat-
ment for fecal incontinence.
There is some nonspecificity associated with stimula-
tion of the sacral nerves demonstrated by the knowledge
that sacral nerve stimulation affects not only fecal incon-
tinence, but also urinary incontinence, urinary reten-
tion, constipation, and pain in the pelvic floor because of
the combined effects on the central, sensory, and motor
1290 DAMASER ET AL: ELECTRICAL STIMULATION: ANAL SPHINCTER

A B C
Pressure (cm H2O) Pressure (cm H2O) Pressure (cm H2O)
25 8 16
*
6 * 14
*
20
12
4
15 10
2
8
10 0 6

–2 4
5
2
–4

Beginning Middle End Rest Beginning Middle End Rest Beginning Middle End Rest

D E F
Pressure (cm H2O) Pressure (cm H2O) Pressure (cm H2O)
+ 12 20
* +
20
8
* 15

10
10 4
5

0 0 0

–4 5
–10

Beginning Middle End Rest Beginning Middle End Rest Beginning Middle End Rest

FIGURE 5. Anal sphincter pressure changes due to anal sphincter stimulation. Change in maximum (A), minimum (B), and average (C) anal
sphincter spontaneous contraction pressure and maximum (D), minimum (E), and average (F) anal sphincter baseline pressure. * = a significant
difference in comparison with stimulation at the end of anal sphincter contraction; + = a significant difference in comparison with stimulation
in the middle of anal sphincter contraction. Each bar represents the mean ± SEM of data from 4 animals.

pathways.26 The pudendal nerve shares common sensory-
motor innervation to the clitoris, urethra, and the striated
muscle of the anal sphincter.27 Thus, it could potentially
be used as a specific target when using electrical stimula-
tion for fecal incontinence, limiting and focusing its ef-
fects to the lower urinary tract and anal sphincter without
unwanted side effects. This study focused on anal sphinc-
ter and bladder pressure after stimulation of the puden-
dal nerve or the anal sphincter. Although increases in anal
sphincter pressure have not been proven to indicate con-
tinence of stool, anal pressures reflect the strength of the
anal sphincter and can be used as a functional surrogate
for fecal incontinence.28,29 To this end, we investigated the
effects of changing stimulation parameters and timing of
stimulation on anal and bladder pressures.
Of all the parameters used in the study, current and
frequency were identified as the parameters that had the
greatest impact on anal and bladder pressures attributed
to electric stimulation, as other studies of stimulation and
in various organs have demonstrated previously.30–33 Anal
sphincter stimulation required less current than pudendal
nerve stimulation to generate similar responses, particu-
larly at higher currents, perhaps because of the stimula-
tion of nerve branches in the sphincter, the muscle itself,
or the combination of the 2. In addition, anal sphincter
stimulation generated less bladder pressure involvement,
presumably because the anal sphincter stimulation elec-
trodes were in direct contact with the muscle causing an
immediate and strong anal sphincter contraction. When
higher currents were used for anal sphincter stimulation,
bladder pressure also increased. This was secondary to
stimulation of abdominal muscles causing increased pres-
sure on the bladder, as demonstrated by the lack of blad-
der response after transection of the abdominal muscles.
Electrical stimulation reliably resulted in changes in
anal sphincter pressure, although changes were also noted
in bladder pressure. Significant anal sphincter pressure in-
creases were observed to achieve their greatest extent when
stimulation was applied at the beginning of anal sphincter
contraction. This could be the result of electric stimulation
DISEASES OF THE COLON & RECTUM VOLUME 55: 12 (2012) 1291

A B C
Pressure (cm H2O) Pressure (cm H2O) Pressure (cm H2O)
10 *
–12 –6
*
8 4 *
5
4
2

0
0 0

–4
–2

Beginning Middle End Rest Beginning Middle End Rest Beginning Middle End Rest

D E F
Pressure (cm H2O) Pressure (cm H2O) Pressure (cm H2O)
+
10
+ 10 *
*
8
5 4
4
0
0
0
–5
–5
–4
–10

Beginning Middle End Rest Beginning Middle End Rest Beginning Middle End Rest

FIGURE 6. Anal sphincter pressure changes due to pudendal nerve stimulation. Change in maximum (A), minimum (B), and average (C) anal
sphincter spontaneous contraction pressure and maximum (D), minimum (E), and average (F) anal sphincter baseline pressure. * Indicates a
significant difference in comparison with stimulation at the end of anal sphincter contraction. + Indicates a significant difference in comparison
with stimulation in the middle of anal sphincter contraction. Each bar represents the mean ± SEM of data from 4 animals.

facilitating the spontaneous anal sphincter contraction
that was already beginning.34 Stimulation at the end of a
spontaneous anal sphincter contraction did not result in
a significant increase in anal sphincter pressure, probably
because, at the end of a muscle contraction, the closing
of Na+ channels coupled with the opening of K+ chan-
nels makes muscle cells less responsive to the incoming
electrical stimulus.35 Our results suggest that the timing of
stimulation may be considered as an important factor for
optimal stimulation of anal sphincter and restoration of fe-
cal incontinence.
Few other investigators have measured anal sphincter
pressures in experimental animals,35,36 and even fewer have
investigated the effects of electrical stimulation on these
pressures.37 We used rats in our experiment because of their
availability and the extensive information available regard-
ing the innervation and physiology of the anal sphincter in
rats.12,17 However, rats are small, increasing the possibility
of spread of the electrical stimulation to other tissues, par-
ticularly at higher currents. For this reason, we transected
the pudendal nerve proximal and distal to the stimulat-
ing electrodes to investigate if the observed effects on anal
sphincter and bladder pressure were due to current trans-
mission along the pudendal nerve or via spread of the sig-
nal to other tissues. The increase in anal sphincter pressure
was eliminated by transection of the pudendal nerve distal
to the electrodes in all animals, demonstrating that the pri-
mary means of stimulation-activated signal transmission is
via stimulation of the motor branch of the pudendal nerve,
which innervates the anal sphincter,27 and that spread of the
electrical signal had only a negligible effect.
We performed a similar experiment on animals un-
dergoing anal sphincter stimulation by transecting the ab-
dominal musculature to determine whether the increase
in bladder contraction was due to contraction of abdomi-
nal muscles pressing on the bladder, rather than via direct
stimulation of the bladder. Abdominal muscle transec-
tion eliminated the bladder pressure increase due to anal
sphincter stimulation in all animals, indicating that, at high
currents, stimulation spread from the anal sphincter to the
1292 DAMASER ET AL: ELECTRICAL STIMULATION: ANAL SPHINCTER

A B
Pressure (cm H2O) Pressure (cm H2O)
100 80

80 60

60 40

40 20

20 0

0 10 20 30 40 50 60 70 0 20 40 60 80
Times (seconds) Times (seconds)

C D
Pressure (cm H2O) Pressure (cm H2O)
30 35

30
25
25
20
20

15 15

10
10
5
5
0

0 20 40 60 80 100 0 10 20 30 40 50 60 80
Times (seconds) Times (seconds)

FIGURE 7. Bladder (solid line) and anal sphincter (dashed line) pressure in response to anal sphincter stimulation before (A) and after (B)
transecting abdominal muscles as well as in response to pudendal nerve stimulation before (C) and after (D) transecting the pudendal nerve
distal to the stimulation. Muscle transection eliminated the increase in bladder pressure due to anal sphincter stimulation. Distal nerve
transection eliminated the increase in anal sphincter pressure due to stimulation of the pudendal nerve. The thick horizontal bar indicates
timing and duration of stimulation. Stimulation settings for each example are given above the graph. ma = current (mA); pps = frequency (Hz);
s = duration (seconds); us = pulse duration (µsec); AS = anal sphincter stimulation; NS = pudendal nerve stimulation.

abdominal muscles in these small experimental animals.
For clinical utilization of direct anal sphincter stimulation,
stimulation current values could be set below the threshold
for abdominal muscle involvement.
The anesthesia used in this experiment could have
affected bladder and anal sphincter pressures and may
potentially not well represent these values in a conscious
animal. We used a standard method of anesthetizing ani-
mals for physiological recordings, and we have previously
demonstrated that this anesthetic successfully maintains
spontaneous anal sphincter contractions.12,17 Because an-
esthesia is needed for measurement of anal sphincter pres-
sure in rats, we included assessment of 2 control rats. These
animals maintained consistent bladder and anal sphincter
pressures throughout the anesthesia period, demonstrat-
ing that the effects observed in the experimental animals
were not time dependent.
Animal models have been previously used to test new
therapeutic options for both urinary and fecal inconti-
nence.38–41 Although this study focuses on a short stimula-
tion, continuous stimulation of the sacral nerve has been
investigated both in animal models and clinical studies for
both urinary and fecal incontinence.10,42–44 Furthermore,
chronic pudendal nerve stimulation has been attempted
DISEASES OF THE COLON & RECTUM VOLUME 55: 12 (2012)
with a small number of patients. 13 Therefore, chronic
stimulation of the anal sphincter or pudendal nerve may
be useful to investigate in the future both preclinically in
chronic animal models and in clinical trials. Currently
there is an interest in pursuing pudendal nerve stimula-
tion as a therapeutic option, and this study could be the
basis for future clinical research.
ACKNOWLEDGEMENTS
The authors thank Brian Balog and David Sypert for their
assistance.
REFERENCES
1. Altman D, Ekström A, Forsgren C, Nordenstam J, Zetterström
J. Symptoms of anal and urinary incontinence following cesar-
ean section or spontaneous vaginal delivery. Am J Obstet Gyne-
col. 2007;197:512.e1–512.e7.
2. Handa VL, Zyczynski HM, Burgio KL, et al; Pelvic Floor Disor-
ders Network. The impact of fecal and urinary incontinence on
quality of life 6 months after childbirth. Am J Obstet Gynecol.
2007;197:636.e1–636.e6.
3. Kapoor DS, Thakar R, Sultan AH. Combined urinary and
faecal incontinence. Int Urogynecol J Pelvic Floor Dysfunct.
2005;16:321–328.
4. Lien KC, Morgan DM, Delancey JO, Ashton-Miller JA. Puden-
dal nerve stretch during vaginal birth: a 3D computer simula-
tion. Am J Obstet Gynecol. 2005;192:1669–1676.
5. Goldman HB, Amundsen CL, Mangel J, et al. Dorsal geni-
tal nerve stimulation for the treatment of overactive bladder
symptoms. Neurourol Urodyn. 2008;27:499–503.
6. Starkman JS, Wolter CE, Scarpero HM, Milam DF, Dmochows-
ki RR. Management of refractory urinary urge incontinence
following urogynecological surgery with sacral neuromodula-
tion. Neurourol Urodyn. 2007;26:29–36.
7. Gill BC, Swartz MA, Firoozi F, et al. Improved sexual and uri-
nary function in women with sacral nerve stimulation. Neuro-
modulation. 2011;14:436–443.
8. Altomare DF, Rinaldi M, Petrolino M, et al. Permanent sacral
nerve modulation for fecal incontinence and associated uri-
nary disturbances. Int J Colorectal Dis. 2004;19:203–209.
9. Matzel KE, Lux P, Heuer S, et al. Sacral nerve stimulation for
faecal incontinence: long-term outcome. Colorect Dis. 2009;11:
636–641.
10. Mellgren A, Wexner SD, Coller JA, et al; SNS Study Group.
Long-term efficacy and safety of sacral nerve stimulation for
fecal incontinence. Dis Colon Rectum. 2011;54:1065–1075.
11. Wexner SD, Coller JA, Devroede G, et al. Sacral nerve stimula-
tion for fecal incontinence: results of a 120-patient prospective
multicenter study. Ann Surg. 2010;251:441–449.
12. Zutshi M, Salcedo LB, Zaszczurynski PJ, Hull TL, Butler RS,
Damaser MS. Effects of sphincterotomy and pudendal nerve
transection on the anal sphincter in a rat model. Dis Colon Rec-
tum. 2009;52:1321–1329.
13. George AT, Dudding TC, Nicholls RJ, Vaizey CJ. A new mini-
mally invasive technique for pudendal nerve stimulation.
Colorectal Dis. 2012;14:98–103.
1293
14. Damaser MS, Broxton-King C, Ferguson C, Kim FJ, Kerns
JM. Functional and neuroanatomical effects of vaginal dis-
tention and pudendal nerve crush in the female rat. J Urol.
2003;170:1027–1031.
15. Butler R. Experimental designs. In: Kattan M, ed. The Encyclo-
pedia of Medical Decision Making. Vol 1. Thousand Oaks, CA:
Sage Publications; 2009:489–493.
16. Schmidt SR, Launsby RG. Understanding Industrial Designed
Experiments. 4th ed. Colorado Springs, Colorado: Air Academy
Press; 2004.
17. Salcedo L, Damaser M, Butler R, Jiang HH, Hull T, Zutshi M. Long-
term effects on pressure and electromyography in a rat model of
anal sphincter injury. Dis Colon Rectum. 2010;53:1209–1217.
18. Bharucha AE, Zinsmeister AR, Locke GR, et al. Risk factors for
fecal incontinence: a population-based study in women. Am J
Gastroenterol. 2006;101:1305–1312.
19. Nelson RL. Epidemiology of fecal incontinence. Gastroenterol-
ogy. 2004;126(1 suppl 1):S3–S7.
20. Uustal Fornell E, Wingren G, Kjølhede P. Factors associated
with pelvic floor dysfunction with emphasis on urinary and
fecal incontinence and genital prolapse: an epidemiological
study. Acta Obstet Gynecol Scand. 2004;83:383–389.
21. Donnelly V, Fynes M, Campbell D, Johnson H, O’Connell PR,
O’Herlihy C. Obstetric events leading to anal sphincter dam-
age. Obstet Gynecol. 1998;92:955–961.
22. Safioleas M, Andromanakos N, Lygidakis N. Anorectal incon-
tinence: therapeutic strategy of a complex surgical problem.
Hepatogastroenterology. 2008;55:1320–1326.
23. Malouf AJ, Norton CS, Engel AF, Nicholls RJ, Kamm MA.
Long-term results of overlapping anterior anal-sphincter re-
pair for obstetric trauma. Lancet. 2000;355:260–265.
24. Zutshi M, Tracey TH, Bast J, Halverson A, Na J. Ten-year out-
come after anal sphincter repair for fecal incontinence. Dis Co-
lon Rectum. 2009;52:1089–1094.
25. Altomare DF, Ratto C, Ganio E, Lolli P, Masin A, Villani RD.
Long-term outcome of sacral nerve stimulation for fecal incon-
tinence. Dis Colon Rectum. 2009;52:11–17.
26. Dudding TC. Future indications for sacral nerve stimulation.
Colorectal Dis. 2011;13(suppl 2):23–28.
27. Pastelín CF, Zempoalteca R, Pacheco P, Downie JW, Cruz
Y. Sensory and somatomotor components of the “sensory
branch” of the pudendal nerve in the male rat. Brain Res.
2008;1222:149–155.
28. Norton C, Gibbs A, Kamm MA. Randomized, controlled trial
of anal electrical stimulation for fecal incontinence. Dis Colon
Rectum. 2006;49:190–196.
29. Vaizey CJ, Kamm MA, Turner IC, Nicholls RJ, Woloszko J. Effects
of short term sacral nerve stimulation on anal and rectal func-
tion in patients with anal incontinence. Gut. 1999;44:407–412.
30. Dudding TC, Vaizey CJ, Gibbs A, Kamm MA. Improving the ef-
ficacy of sacral nerve stimulation for faecal incontinence by al-
teration of stimulation parameters. Br J Surg. 2009;96:778–784.
31. Moreau C, Defebvre L, Destée A, et al. STN-DBS frequency ef-
fects on freezing of gait in advanced Parkinson disease. Neurol-
ogy. 2008;71:80–84.
32. Wachter D, Wrede A, Schulz-Schaeffer W, et al. Transcranial di-
rect current stimulation induces polarity-specific changes of cor-
tical blood perfusion in the rat. Exp Neurol. 2011;227:322–327.
33. Hamani C, Hodaie M, Chiang J, et al. Deep brain stimulation
of the anterior nucleus of the thalamus: effects of electrical
1294
stimulation on pilocarpine-induced seizures and status epilep-
ticus. Epilepsy Res. 2008;78:117–123.
34. Goodman BE. Channels active in the excitability of nerves
and skeletal muscles across the neuromuscular junction: b ­ asic
function and pathophysiology. Adv Physiol Educ. 2008;32:
127–135.
35. Healy CF, O’Herlihy C, O’Brien C, O’Connell PR, Jones JF.
Experimental models of neuropathic fecal incontinence: an
animal model of childbirth injury to the pudendal nerve
and external anal sphincter. Dis Colon Rectum. 2008;51:
1619–1626.
36. Tieppo J, Kretzmann Filho NA, Seleme M, Fillmann HS,
Berghmans B, Possa Marroni N. Anal pressure in experimental
diabetes. Int J Colorectal Dis. 2009;24:1395–1399.
37. Song GQ, Zhu H, Chen JD. Effects and mechanisms of vaginal
electrical stimulation on rectal tone and anal sphincter pres-
sure. Dis Colon Rectum. 2007;50:2104–2111.
38. Berkley KJ, Robbins A, Sato Y. Functional differences between
afferent fibers in the hypogastric and pelvic nerves innervating
female reproductive organs in the rat. J Neurophysiol. 1993;69:
533–544.
DAMASER ET AL: ELECTRICAL STIMULATION: ANAL SPHINCTER
39. Brading AF, Ivancheva C, Radomirov R. Functional coordina-
tion of motor activity in colonic and recto-anal smooth muscles
in rat experimental model. Methods Find Exp Clin Pharmacol.
2008;30:201–207.
40. Chang HY, Cheng CL, Chen JJ, Peng CW, de Groat WC. Re-
flexes evoked by electrical stimulation of afferent axons in the
pudendal nerve under empty and distended bladder condi-
tions in urethane-anesthetized rats. J Neurosci Methods. 2006;
150:80–89.
41. Scheepens WA, de Bie RA, Weil EH, van Kerrebroeck PE. Uni-
lateral versus bilateral sacral neuromodulation in patients with
chronic voiding dysfunction. J Urol. 2002;168:2046–2050.
42. Brazzelli M, Murray A, Fraser C. Efficacy and safety of sacral
nerve stimulation for urinary urge incontinence: a systematic
review. J Urol. 2006;175(3 pt 1):835–841.
43. Leroi AM, Michot F, Grise P, Denis P. Effect of sacral nerve
stimulation in patients with fecal and urinary incontinence.
Dis Colon Rectum. 2001;44:779–789.
44. Oerlemans DJ, van Kerrebroeck PE. Sacral nerve stimulation for
neuromodulation of the lower urinary tract. Neurourol Urodyn.
2008;27:28–33.