Optimal Frequency Used in Transcutaneous Electrical Nerve Stimulation (TENS) for Treating Pelvic Pain in Adults
Phase: NA
Conditions: Chronic Pelvic Pain
Sponsor: Albany Medical College

 
 
 
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Version Date: 5/14/2022 
 
 
 
 
Optimal Frequency Used in Transcutaneous Electrical Nerve 
Stimulation (TENS) for Treating Pelvic Pain in Adults 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PRINCIPAL INVESTIGATOR: 
 
 
Elise JB De, MD 
 
Department of Surgery, Division of Urology 
 
 
 
Albany Medical College 
 
 
 
23 Hackett Boulevard 
 
 
 
Albany, NY  12208 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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A. STUDY BACKGROUND AND PURPOSE 
Pelvic pain can be a debilitating and often frustrating condition as its origin is not always 
known. Pelvic pain can present as interstitial cystitis/bladder pain syndrome, sexual pain 
syndrome, prostate pain syndrome, scrotal pain syndrome, urethral pain syndrome, vaginal and 
vulvar pain syndromes, myofascial pain syndromes, and prolapse/incontinence mesh pain. These 
conditions can be multidisciplinary in nature involving overlap of etiology: urologic, 
gynecologic, gastroenterological, neurologic and even psychiatric. There are dozens of etiologies 
of pelvic pain, and causes can be multiple or unknown (1).  
 
Each different pain modality has potential treatment targets. Historically treatments have 
been differentiated, rather than on etiology, but with a blanket approach: anti-inflammatories 
such as steroids or NSAIDs if pain was of the “-itis” etiology and treated with antibiotics if 
presumed to be of an infectious nature (4). We currently know much more about pain as a 
disease state and as we continue to unravel more about chronic pelvic pain. Treatment modalities 
have likewise become more accurate in their scope. Currently the AUA/EAU has treatment 
specific guidelines for how to algorithmically approach each different lineage of pelvic pain 
based on its origin and likely nature of the primary cause. Some modalities of pain have more 
rigorous data then others for their treatment. However, one new emerging therapy for the 
treatment of pelvic pain across many etiologies is the use of the TENS unit and transcutaneous 
stimulation of the posterior tibial nerve (1,3,4). The literature on the use of this modality for 
pelvic pain is still emerging. Traditionally TENS units in chronic pain have been extensively 
studied to show benefit in conditions such as knee, back, shoulder and even menstrual pains. 
Less studied is the use of TENS units as a noninvasive and low risk modality to help alleviate 
chronic pelvic pain of heterogeneous etiologies. Importantly, it also puts control into the 
participants’ hands, can be used as an adjunct to existing strategies, and expands the options for 
regaining quality of life. 
 
A systematic review identified 8 Randomized controlled trials, 1 Crossover trial, 4 
Randomized trials, 18 Prospective cohort studies, 5 Retrospective case series investigating 
neuromodulation for pelvic pain, including implanted sacral nerve stimulators, needle-based 
posterior tibial nerve stimulators, and transcutaneous TENS units. The 8 RCTs showed a 
significant reduction in pain following twelve weeks of treatment for pain conditions including 
dysmenorrhea and chronic pelvic pain by a variety of objective and subjective measures. 
However, there appeared to be conflicting evidence when it came to QoL measures. The 
beneficial effects specifically of a course of TENS may be sustained beyond 12 weeks; one study 
showed a persistent benefit at 43 months in 73% of men with chronic pelvic pain and another 
demonstrated a prolonged significant improvement in women with provoked vestibular pain at 
ten months post-trial for those who opted to continue therapy. Overall, there were few adverse 
events cited. In sum, neuromodulation in general and TENS in particular have been shown to be 
successful for chronic pelvic pain (3). Stronger data, however, is needed, in particular for the 
non-invasive transcutaneous electrical nerve stimulation as an option for participants with 
chronic pelvic pain.  Its applications in general have not been explored fully and specifically the 
technical parameters – settings and placement sites - have not been delineated for optimal results.  
 
 

 
 
 
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Placement: The studies in the table below have used TENS or some other form of 
neuromodulation for chronic pelvic pain. One used the posterior tibial nerve transcutaneously, 
and many others used the sacral region or pelvic region (15,16,17). Based on a recent study in 
manuscript submission demonstrating superior outcomes for posterior tibial placement in 
bedwetting, we will study the tibial site of application. 
 
Our proposal is to study pain outcomes with different frequencies of stimulation. We will 
employ the posterior tibial nerve location and by varying the frequency (pulse rate, Hz) will 
identify the most effective setting for pelvic pain modulation by application of a TENS Unit.  We 
will use a fixed pulse width of 200 microseconds, with continuous rather than biphasic 
stimulation, based on expert input from 5 colleagues with experience in electrophysiology and 
usage of TENS. Frequencies and pulse widths previously studied are summarized as follows (3): 
 
Study 
Frequency 
(Pulse 
Rate, Hz) 
Width (Pulse 
Width, 
Microseconds) 
Amplitude 
Comments 
Effect 
Bai 
2–100 
 
 
Transcutaneous 
Posterior Tibial, 
Dysmenorrhea, 
frequency not 
controlled or 
compared  
Efficacious 
for 
Dysmenorrhe
a 
Lauretti 
85 
 
variable 
Transcutaneous 
Suprapubic, 
Dysmenorrhea 
Efficacious 
for 
dysmenorrhea 
pain and 
QOL 
Lee 
100 
100 
 
TENS lower 
abdomen and 
thermotherapy for 
Dysmenorrhea 
Efficacious 
for 
dysmenorrhea 
pain and 
QOL 
Buffenoir 
100-200 
1.4-8.7 
 
Implanted spinal 
cord stimulation 
for pudendal 
neuralgia 
Efficacious 
for 
decreasing 
pain 
Comiter 
16 
210 
 
Sacral nerve 
stimulation, 
Interstitial cystitis 
Effective to 
reduce pain 
Ghazwani 
14 
200 
 
Sacral nerve 
stimulation, 
Bladder pain 
syndrome 
Effective to 
reduce pain 

 
 
 
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Kaplan  
100 
95 
50 
TENS, 
Dysmenorrhea, 
Effective for 
pain 
Kim 
20 
 
10 
PTENS(Percutane
ous electrical 
nerve 
stimulation), 
chronic pelvic 
pain 
May be 
helpful for 
pain but was 
not 
statistically 
significant 
Maher 
15 
210 
 
Percutaneous S3 
Sacral Nerve 
Stimulation, 
Interstitial Cystitis 
Improved 
pelvic pain, 
nocturia 
Schneider 
80 
150 
 
Transcutaneous 
penile electrodes, 
pain scale and 
QOL 
Reduced pain 
and increased 
QOL 
Tugay 
120 
100 
 
Transcutaneous 
Lower Back, 
Dysmenorrhea 
Not 
statistically 
significant for 
dysmenorrhea 
Vallinga 
80 
50-180 
 
TENS (Location 
not specified), 
Vestibulodinia 
Reduced 
Vulvar pain 
Van 
Balken 
20 
200 
0-10 
Percutaneous, 
Posterior tibial 
nerve, Chronic 
pelvic pain 
Reduced pain 
and improved 
QOL 
 
The goal of the current study is to determine which pulse rate (Hz) is the most effective to use in 
posterior tibial transcutaneous electric nerve stimulation for treating pelvic pain given a set 
location (posterior tibial nerve) and Pulse Width (200 microseconds) on continuous stimulation. 
 
 
Specific Aim:  To determine if a low (Group 1, 20 Hz), medium (Group 2, 50Hz), or high 
(Group 3, 100 Hz) pulse rate (frequency) used in posterior tibial TENS is better in improving 
pelvic pain (as measured by decreased Visual Analog Scale (VAS) scores and improved pain, 
urinary and QOL scales on the validated Genitourinary Pain Index (GUPI). 
 
Hypothesis:  A high frequency (100 Hz) used in TENS will show the most improvement in 
pelvic pain compared to low and medium frequencies.  
 
B. STUDY DESIGN 
Adults ages 18-90 years old referred to the Urology and Multidisciplinary Pelvic Health clinics 
at Albany Medical Center for chronic refractory pelvic pain will be screened for enrollment and 
offered participation. Participants who have first been given the standard of care therapy 

 
 
 
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according to the AUA/EUA guidelines depending on their specific pain modality, first line 
treatments based on suspected etiology (for example pelvic floor physical therapy for high tone 
pelvic floor muscle dysfunction or amitriptyline for interstitial cystitis) without success will be 
defined as refractory. Participants who have plateaued on their response to current intervention 
strategies will be offered the TENS unit as an adjunct.  
 
Participation will be offered by mail or in person.  If by mail, we will send the consent with the 
letter and questionnaires asking participants to call or bring the material if they would like to 
enroll. If we speak to the subject over the phone, we will discuss the study as comprehensively as 
if they were in the clinic. This will include explaining the concept of the TENS unit, the study 
itself, and clarifying any questions the participant has. Subsequently if they are interested in the 
study, we will ask them to sign the consent and return it to us via mail or email.  Once we receive 
the consent we will sign and document the reason for the difference in signature dates.  
 
Those whose pain symptomatology is above a threshold and who choose TENS therapy will be 
included in the study (4).  Participants who have recently initiated new pharmacologic treatment 
or alternative therapy for pelvic pain (or related urologic disorders) within the past 30 days, who 
cannot work a TENS unit, or who report prior use of a TENS unit or other neuromodulation for 
chronic pain, and those who have any contraindications to usage of a TENS unit (such as having 
a pacemaker or an adhesive allergy) will be excluded.   
 
The participants will be randomized into three groups of 25 participants each. The randomization 
will occur in blocks so that if we need to terminate the study early there will be an equal number 
of participants in each group. The size of the blocks will also be kept secret for allocation 
concealment purposes. The randomization will be stratified by gender so that there is an equal 
number of participants from each gender in each group, reducing potential for gender as a 
confounding variable. Group 1 will be the low frequency set at 20 Hz.  Group 2 will be the 
medium frequency set at 50 Hz.  Group 3 will be the high frequency set 100 Hz.  There is no 
sham group in this study as it has previously been found that posterior tibial TENS is effective 
and lasting. As such, all participants will be treated as a matter of routine medical care for pelvic 
pain. We will use a fixed pulse width of 200 microseconds (uS), with continuous rather than 
biphasic stimulation based on input from 5 colleagues with expertise in neurophysiology and 
TENS and on the above literature review. We will aim to recruit 25 participants per group for a 
total of 75 participants.  
 
Study Procedures 
Participants with chronic/persistent pain that has been continuous or recurrent for at least three 
months (in accordance with EAU Guideline definition) who have failed first line treatment will be 
advised of the study. All participants will be asked if they have an adhesive allergy and medical 
record reviewed for this allergy as this will exclude them from the study. A detailed explanation 
of the purpose of the study, along with the risks and benefits of TENS will be given to the 
participant by a provider prior to obtaining informed consent for enrollment into the study. After 
informed consent has been obtained, if the participant is of childbearing potential, a urine 
pregnancy test will be conducted. The participant will be excluded from participation if pregnant 
and referred for appropriate care.  
 

 
 
 
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Study Schedule Overview: 
 
Standard 
Visit 
Billed in 
Part to 
Insurance 
Just a 
Study 
Visit 
Virtual 
Phone 
or 
Video 
is an 
Option 
In 
Person 
Only 
Questionn-
aires: 1-10 
pain scores 
and GUPI 
Usage Chart 
Completed 
(During 
phase when 
TENS being 
Used) 
Treatment 
Map 
Completed
/ Updated 
with Dates 
Adjusting 
TENS 
Settings 
Permitted 
New 
Treatments 
outside of 
pre-
existing 
treatment 
and TENS 
Permitted 
Week 1 – 
Phone 
Call in 
Response 
to Mailer 
 
√ 
√ 
 
√ 
 
√ 
 
 
Week 1 – 
Occurring 
as Part of 
Regular 
Office 
Visit 
√ 
 
√ 
 
√ 
 
√ 
 
 
Week 2 
√ 
 
 
√ 
√ 
 
 
 
 
Week 3 
 
√ 
√ 
 
√ 
√ 
√ 
 
 
Week 4 
√ 
 
√ 
 
√ 
√ 
√ 
 
 
Optional 
Week 8 
 
√ 
√ 
 
√ 
√ 
√ 
√ 
√ 
Optional 
Week 12 
 
√ 
√ 
 
√ 
√ 
√ 
√ 
√ 
Optional 
Week 16 
√ 
 
√ 
 
√ 
√ 
√ 
√ 
√ 
 
 
Screening Day 7/ Week 1 (in clinic or virtual): The first data points (Day 0) will take place in the 
clinic during the participant’s routine visit or at the time of the participant’s phone call seeking 
participation. If during a phone call seeking participation, this will be considered a study phone 
call, not a billable visit. The participant will fill out the VAS and GUPI. The participants will be 
taught how to fill out the pain assessment questionnaires (the VAS and GUPI, validated tools for 
measuring genitourinary pain and symptoms respectively). This can be done via paper to be 
brought into the office at their next checkup or via an emailed link through Qualtrics and uploaded 
to a spreadsheet in a protected AMC OneDrive. The baseline pain logs will be reviewed for 
sufficient severity of pain episodes and the participant will be randomized into the study if their 
pain is above the designated threshold: participants who record a pain scale of 4 or higher on any 
of the VAS scores or QOL score of 3 or higher on the GUPI question #9 will be eligible for the 
TENS study. Those who record lower scores will be ineligible for the TENS study but will be 
offered therapy in according to the AUA/EUA guidelines using the recommended second or third 
line therapies for their specific pain etiology, including a trial of a TENS unit.  
 
The GUPI and VAS will be collected at this time; this will record the participant’s pain 1 week 
prior to the study and will be considered Day 7/week 1. The week 1 of screening will be 
combined with the first week of baseline measurement (week 2) for a 2-week lead-in.  
Participants will be taught how to complete a usage log (stating if the TENS was used each day 
and for how long in minutes) and will be asked to repeat this weekly. Participants will complete 

 
 
 
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an inventory (the Treatment Map) of treatments tried prior to the TENS, throughout the study, 
and at the end.  
 
Baseline Day 14/ Week 2: If the participant enrolls, they will be asked to continue logging pain 
(VAS and GUPI, on paper or via Qualtrics) for one week, with the week 1 screening and the 
week 2 baseline week totalling a 14-day control period. The control period will represent data (2 
weeks of VAS and GUPI) with only baseline treatments and no TENS unit.  
 
At week 2 (the end of the 2-week baseline, in person), participants will hand in scores and be 
randomized to a frequency. Part of this 60-minute visit will be considered standard of care, a level 
3, 20-minute educational visit on a commonly used treatment option. They will be given a TENS 
unit and taught how to use the unit. Teaching will include positioning of electrodes, as well as 
what buttons they are allowed to manipulate. The TENS unit settings will be pre-determined at the 
clinic and measures will be taken to ensure that the settings cannot be altered at home. The 
participant will be instructed not to open the TENS unit during the 2 treatment weeks of the study 
to ensure the settings are maintained. They will be instructed to continue only their baseline 
treatments. 
 
 
 
Settings: The TENS unit used is a Compass Health TENS 3000, 3 mode Analog Unit. The 
participants’ TENS unit will be set at Normal Mode (N), a pulse width of 200 microseconds and 
an intensity to be determined in the office based upon when the participant feels sensitive to the 
TENS unit. Frequency (pulse rate) will be determined by randomization. The participant will place 
the electrodes along the posterior tibial nerve on the medial ankle with a ground on the inner arch, 
each day for 30 minutes for a total of 14 days at the time of day typically associated with the worst 
pain or at the first opportunity for rest after this time. 
 
Group 1 will be the low frequency group.  This means that the TENS therapy will use a 
frequency of 20 Hz.   
 

 
 
 
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Group 2 will be the medium frequency group.  This means that the TENS therapy will use a 
frequency of 50 Hz.  
 
Group 3 will be the high frequency group.  This means that the TENS therapy will use a 
frequency of 100 Hz.  
 
 
Participants will be provided the TENS unit, its manual, and enough patches to last the 2 weeks 
of the treatment period. Participants will be given a weekly usage log, weekly pain VAS and 
weekly GUPI questionnaire logs again for 2 weeks they are actively using the TENS, with the 
option of paper or Qualtrics.  In this log, the rating of pain by VAS and GUPI, the rating of 
genitourinary symptoms by GUPI, duration of TENS therapy, usage for every day of the week 
and adverse reactions to the TENS unit (rash) will be recorded. 
 
Participants may be called during the 14-day treatment period to keep on track, address any 
concerns, questions, or any adverse reactions to TENS therapy by the physician or research staff. 
Their phone numbers will be maintained in the master key associated with the deidentified 
database in the AMC Onedrive protected research file for this purpose. 
 
At 7 days and the end of the 14-day treatment period the visit can be performed either virtually 
or in the office. The 7-day visit will be considered purely a study visit and the 14 day visit a 
standard of care visit. 
 
The completed week 3 and 4 VAS and GUPI, treatment usage documents will be returned. The 
participants will also be asked the question “Will you continue using TENS therapy for your 
pelvic pain?”  Any persistent issues will be addressed during these visits as well and further 
options discussed.  
 
For those who would like to continue the TENS unit, participants will be taught how to adjust 
settings and sites at home. Participants will be given repeat VAS and GUPI at 1, 2, and 3 months 
post-initial phase and seen again at 3 months as part of standard care. Here we will review logs 
of what frequency patterns they developed with TENS usage on their own, if any. In this time 
participants may increase or decrease the frequency of their device anywhere in the range of 2 
Hz to 150 Hz to see which they prefer most in this part of the trial. Participants will also be 
allowed to adjust pulse width (30 to 260 uS), mode (B N M), time (continuous, 15, 30 minutes), 
and intensity (1 to 8, 10-80mA) as desired. The only requests will be that they remove the device 
if any discomfort occurs and that they log their settings versus their response. 
 
Note: 
TREATMENT MODE (B, N, M): 
Normal (Continuous, Conventional) TENS offers the practitioners complete control over all the 
various treatment parameters of the instrument. Burst Mode is analogous to the Low Rate TENS 
technique except the low frequency individual pulses are replaced by individual "bursts" of 7-10 
individual pulses. It is thus a combination of Conventional TENS and Low Rate TENS. In Burst 
Mode, the treatment frequency is fixed by the instrument and is not adjustable with the 
Frequency Rate control. Participants will be educated about this. Modulated Mode attempts to 

 
 
 
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prevent nerve accommodation by continuously cycling the treatment intensity. When using 
Modulated Mode increase the intensity only when the unit is at the maximum intensity of the 
modulation cycle. If the intensity is increased during a low intensity period of the cycle, the 
participant may turn up the control very slowly, so that they may feel the intensity any higher. 
 
In a future study we will want to look at Normal (more like massage) versus Modulated mode 
(more like acupuncture).  
 
C. SUBJECT POPULATION  (WHO, WHAT, WHERE) 
Inclusion criteria for cases:  
1. Age 18-90 years of age seen at Albany Medical Center Division of Urology 
2. Presenting with chronic pelvic pain (chronic/persistent pain that has been continuous or 
recurrent for at least three months (in accordance with EAU Guidelines).  
3. Unsuccessful initial interventions based on initial assessments 
4. Ability to provide informed consent and complete study requirements 
5. Ability to complete a comprehensive history (including with an interpreter) 
 
Exclusion criteria for cases:  
1. Participants who have previously tried a new pharmacologic treatment for pelvic pain, 
neuromodulation or other alternative therapy for urologic disorders within the past 30 
days 
2. Inability to work a TENS unit 
3. Any contraindications to usage of a TENS unit (pacemaker or other implantable device, 
lymphedema, pregnancy, malignancy, bleeding or clotting disorders, unhealthy tissue, 
seizure disorders, impaired cognition)  
4. Any history of electrophysiologic heart disease or complications 
5. Source of pain being an obvious anatomic issue requiring alternative treatment – for 
example urethral diverticulum, distal ureteric stone. 
6. Participant who is pregnant 
7. Participant with adhesive allergy either reported by the participant or upon chart review 
 
 
D. DATA ANALYSIS 
The data collection list is attached to the protocol. The data will be collected on a deidentified 
excel spreadsheet by participant study number and the deidentified data will be entered into the 
database.  The source documents and informed consents will be kept in the locked Urology 
Research Office. Qualtrics data will be downloaded onto a secure excel spreadsheet that will 
immediately be uploaded to the secure urology one drive. Paper responses will be entered to this 
spreadsheet manually. 
 
The objective of this study is to evaluate which pulse rate (frequency) is the most efficacious in 
transcutaneous electric nerve stimulation (TENS) as a therapeutic option for pelvic pain. The 

 
 
 
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proposed study will be a randomized clinical trial. There will be three treatment arms with no sham 
or control:  
• 1. Group1: TENS frequency is set to 20 Hz 
• 2. Group2: TENS frequency is set to 50 Hz 
• 3. Group3: TENS frequency is set to 100 Hz   
The study will be conducted for a total of 4 weeks (28 days, including the data for the week prior 
to the initial consent, week 1), followed by a 90-day observational period.   
1. Baseline Measurement of chronic pain using the VAS and GUPI with baseline treatment 
for 7 days [Week 1 (at first visit, data from week prior) then at Week 2 as a control period]  
2. Active measurement of chronic pain using the VAS and GUPI as well as weekly usage 
logs during TENS treatment for 2 weeks [Week 3-4]  
3. Durability: We will again collect data at 1, 2, and 3 months after the week visit for those 
who elect to continue, repeating the VAS and GUPI and treatment inventory, asking how much 
the TENS has been used and at what setting, to assess durability and observe participant-directed 
settings.  
 
RANDOMIZATION  
Subjects will be randomly assigned with equal probability to one of the three study groups. 
Randomization will utilize a web site (www.randomization.com) to provide randomization. 
Randomization will occur in blocks so that if the study needs to be terminated early there is an 
equal number of participants in each group at the time of termination. Also, we will stratify groups 
by gender so that there is an equal number of participants from each gender in each group to help 
limit this confounding variable. Allocation-concealment will be achieved by using sealed 
envelopes opened only after subjects are enrolled. Record keeping will be from participant 
responses via Qualtrics before and during TENS treatment.  The scoring of the VAS and GPI 
scales, the compliance rate (used TENS or not), and any participant comments are recorded. 
Participant demographic will include age, gender, and pertinent urological history, if any.   
 
BLINDING  
There will be single blinding. Study participants/caretakers will not know which frequency has 
been assigned.  
 
INTENTION-TO-TREAT  
All subjects will be analyzed according to the intention-to-treat [ITT] principle. A participant will 
be considered evaluable and will be included in the intention-to-treat analysis if the participant has 
documented at least 8 sessions of their designated TENS treatment (about 4 times a week of TENS 
therapy). Analyses that take into account the actual treatment received (e.g., non-compliance, etc.) 
will be carried out as a secondary analysis (per protocol [PP] analysis).  
 
Primary Statistical Objective:  
The primary objective of the study is to compare the three TENS treatment groups after two weeks 
of active treatment, with respect to:  
 
The change in VAS and GUPI pain questionnaires from baseline to after two weeks of 

 
 
 
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therapy.  
The proportion of responders after two weeks of therapy. 
 
Secondary Statistical Objectives:  
Secondary objectives include comparison of the three treatment groups with respect to the rating 
of VAS and GUPI scores, separately, over time (by weekly diary entries). Analysis will be carried 
out to determine if there are time-dependent changes in questionnaire scores across the three TENS 
treatment groups. Urinary symptoms and individual pain site questions will be noted.  
Pairwise comparisons of TENS groups will also be carried out to compare each arm with one 
another using Tukey’s multiple comparison tests.  
We will again collect data at 1,2-, and 3-months post-trial, asking how much the TENS has been 
used, to assess durability.  
 
Outcome Variables and Schedule of Assessments:  
The primary outcome variable of interest is participant’s percentage change in VAS and GUPI 
from before treatment to the end of 2 weeks of active TENS. Also evaluated will be the response 
to treatment each week during the 14-day TENS therapy period and the 2 weeks of observation. A 
participant is said to have a favorable response to the treatment if he/she has a decrease of at least 
2 points on the VAS or 1 point on the GUPI question #9 from baseline to after two weeks of TENS 
therapy. Change in outside interventions will not be permitted during the study but stable therapies 
will be maintained (e.g., medications). 
 
Demographics and participant characteristics will be collected at baseline (age, gender, medical 
history, surgical history, current medications, site of pain, duration of chronic pelvic pain). The 
following outcomes will be measured at baseline, at each week, and at 3 months after the TENS 
therapy month:  
 
• VAS Weekly Scores 
• GUPI Weekly Scores  
 
Statistical Methods  
For the primary objectives:  
• Analysis of variance with a fixed effect of treatment with Tukey’s multiple comparison 
test will be used to test for differences in the reduction in genitourinary symptoms among 
the three treatment arms.  Reduction will be parameterized as a relative change from 
baseline to after the two weeks of treatment. VAS pain response before and after 
treatment will be compared among the three groups using repeated measures ANOVA 
with Tukey’s multiple comparison tests.    
• The Chi-square test or Fisher’s exact test, as appropriate, will be used to compare the 
rates of response among the three treatment arms at the end of the 14-day treatment 
period.  

 
 
 
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For the secondary objectives, a repeated measures analysis of variance will be used to analyze the 
outcomes of interest on a week-to-week basis (improvement in GUPI scores). A treatment-by-time 
interaction will be examined to determine if the patterns of change in GUPI and VAS scores over 
time differ across groups. Adjusted pairwise comparisons (Tukey or Bonferroni method) will be 
used to compare treatment groups to one another.  
Data transformations may be applied, if necessary, in order to meet the required standard model 
assumptions.  
 
Sample Size Considerations  
Power: The number of participants needed was based on a power calculation (ANOVA with 2-
tailed alpha of 0.05) assuming that the minimally important difference to detect among the three 
groups in the change in VAS score would be at least one within-group standard deviation of the 
change in score at 14 days.  With 21 participants per group the power is estimated at 81%.  We 
propose to randomize 25 per group assuming the dropout rate may be as high as 20%.   
     
Based on investigator expertise and some published studies, we assume that the proportions of 
responders based on our criteria of a “favorable response” for each of the three TENS groups will 
be around 40 % (1,2,4,7,10). In our study we are aiming for at least a 40% response rate in our 
complex and refractory population.  
 
 
Conduct of the study 
The principal investigator, Elise De MD, is responsible for overall oversight of the data, 
monitoring the data, assuring protocol compliance, and conducting the safety reviews. The 
principal investigator will also be responsible for compiling the data sheets, day to day oversight 
of research and ensuring the integrity and privacy of the data. During the review process the 
principal investigator, along with the other investigators, will evaluate whether the study should 
continue unchanged, require modification/amendment, or close to enrollment. The principal 
investigators or the Institutional Review Board (IRB) have the authority to stop or suspend the 
study or require modifications. 
 
The master key will house PHI relating to name, address, phone number, MR number and date of 
birth. The secure Qualtrics survey obtained weekly from participants will be securely 
downloaded as an excel spreadsheet into a protected AMC Onedrive file accessible only to study 
personnel. This spreadsheet will be uploaded directly to the secure one drive account to ensure 
participant confidently and security of PHI. Paper surveys will be entered into this database 
within Onedrive. The master key and database will be stores in separate protected Onedrive files.  
 
 
Any worsening symptoms or adverse reactions will be reported to the examiners, by way of pain 
questionnaire, phone calls to participants, the 14-day clinic visits, or reported by participants 
aside from these instances.  For participants with any severe or persistently worsening symptoms 
or adverse reactions, TENS therapy will be immediately discontinued, they will be removed 
from the study and considered to have failed treatment and receive medical treatment as 
necessary.  Skin irritation is the most common adverse reaction to TENS units; however, this is 
mostly associated with allergy to the self-adhesive electrodes (12).  While pain may be a 

 
 
 
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complication with TENS, studies have shown TENS is actually beneficial in treatment of pain 
over different areas of the body (12).  
 
Participants with contraindications to TENS (eg, other electrical devices, pregnancy, bleeding or 
clotting disorders, unhealthy tissue, seizure disorders, malignancy, impaired cognition, adhesive 
allergy) will be excluded from the study.  Participants will be taught safe practice with the use of 
a TENS unit, such as performing a sensory discrimination test in the office, checking and 
cleaning skin before starting a TENS session, monitoring skin for signs of irritation, changing 
adhesive on electrode pads after each use, securing electrodes with even pressure distribution and 
full contact, and watching for signs of TENS unit malfunction requiring maintenance [11].   
 
Participants will be instructed to adjust the intensity to the level they can tolerate, so if the TENS 
intensity is too high then the participants will not be able to tolerate. Pain is the main issue with 
increased intensity (when it is not used to actually treat pain), therefore intensity will be 
minimized as per protocol to prevent this (“to the participant’s perception and tolerance”).  
Increased intensity would be assumed to lead to skin break down, however, reports of this are 
exceedingly rare (13).  Participant education will be comprehensive here.   
 
While reports of dermatitis have been reported in the literature, in most of these cases the 
dermatitis is caused by an allergy to the adhesive on the TENS electrode pads and not the actual 
electrical stimulation.  Skin irritation can occur, but this is mostly seen in cases where TENS 
therapy has been used for multiple hours in a row.  There has been only one case report in the 
literature (and not even searchable in Pubmed) of an actual burn from a TENS unit (14).  In 
contrast, TENS therapy is actually used for pain relief on burn participants.   Therefore, the risk 
of being burned from TENS therapy is extraordinarily low.   
 
The effects of prolonged TENS usage have been studied in the literature before.   
The meta-analysis by Mark Johnson et al showed TENS units to be very safe with very few 
adverse effects seen even for more extended periods of use (10) 
 
 
 
E. RISKS 
 
The risks are minor and unanticipated. If there is any irritation to the participants skin due to the 
adhesive pads the participant will be treated and taken off the study.  
 
Adverse reactions to the TENS units:  The participants will be closely monitored and may be 
called during the treatment period to ensure that the participant is not experiencing any adverse 
reactions to TENS therapy.  Risks can include pain, skin irritation, dermatitis, or burns. The most 
common reaction to the TENS unit is skin irritation related to an allergy to the self-adhesive 
electrodes.   
 
Safe use of TENS units:  The participants will be educated to safely use the TENS unit, 
including monitoring for signs of irritation, changing adhesive on the electrode pads after each 

 
 
 
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Version Date: 5/14/2022 
 
use and securing the electrodes appropriately and alternating the side of each electrode in terms 
of laterality (for example, place the electrode pads on the right foot on one day, then on the left 
foot on the next day, etc). Failure to adhere to safety guidelines could result in an adverse 
reaction to TENS therapy and dismissal from the study.  
 
 Malfunction of the TENS units:  The participants will be taught how to monitor the TENS unit 
they are given for signs of malfunction that will require immediate maintenance. 
 
F. BENEFITS 
Participants enrolled into this study will have failed first-line conventional AUA/EAU treatment 
based on the modality of their pain.  Participants will then be offered TENS therapy and thus 
enrollment into the study as a standard alternative to pharmacologic therapy for pelvic pain based 
on AUA/EAU guidelines and their etiology of pain after proper counseling of the risks and 
benefits by the provider and signing an informed consent. TENS units have been shown to be 
safe with very rare side effects reported in studies.  Participants experiencing side effects or 
adverse reactions to TENS will terminate treatment and receive prompt medical attention.  
Follow up after treatment will determine if continuation of TENS therapy should resume as to 
avoid unnecessary treatment delay with other modalities.   
 
G. CONFIDENTIALITY 
All data will be kept in an excel database file on the secure AMC Onedrive network with access 
restricted to the study personnel which is HIPPAA compliant to protect the confidentiality of 
participants. Consents will be taken in private locations to ensure privacy is not invaded, and 
paper documents locked in the AMC Urology research office file room. 
 
H. OPTIONS 
Rather than participate in this study the subject can opt for standard assessment and care. 
 
I. REFERENCES 
 
1)        Sharma N, Rekha K, Srinivasan JK. Efficacy of transcutaneous electrical nerve 
stimulation in the treatment of chronic pelvic pain. J Midlife Health. 2017 Jan-Mar;8(1):36-39. 
doi: 10.4103/jmh.JMH_60_16. PMID: 28458478; PMCID: PMC5367222. 
2)        Erol B, Danacioglu YO, Peters KM. Current advances in neuromodulation techniques in 
urology practices: A review of literature. Turk J Urol. 2021 Sep;47(5):375-385. doi: 
10.5152/tud.2021.21152. PMID: 35118977. 
3)        Angela M. Cottrell, Marc P. Schneider, Sanchia Goonewardene, Yuhong Yuan, Andrew P. 
Baranowski, Daniel S. Engeler, Jan Borovicka, Paulo Dinis-Oliveira, Sohier Elneil, John 
Hughes, Bert J. Messelink, Amanda C. de C Williams, Benefits and Harms of Electrical, 
European Urology Focus,Volume6,Issue3,2020,Pages559-571,ISSN 
24054569,https://doi.org/10.1016/j.euf.2019.09.011. 
4)        Magnus Fall, Andrew P. Baranowski, Sohier Elneil, Daniel Engeler, John Hughes, Embert 

 
 
 
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Version Date: 5/14/2022 
 
J. Messelink, Frank Oberpenning, Amanda C. de C. Williams,EAU Guidelines on Chronic 
Pelvic Pain,European Urology,Volume 57, Issue 1,2010,Pages 35-48,ISSN 0302-
2838,https://doi.org/10.1016/j.eururo.2009.08.020. 
5)        Christopher Maher, Marcus Carey, Peter Dwyer, Philip Schluter, Percutaneous Sacral 
Nerve Root Neromdulation for Intractable Interstitial Cystitis,The Journal of Urology, Volume 
165, Issue 3,2001,Pages 884-886,ISSN 0022-5347,https://doi.org/10.1016/S0022-
5347(05)66551-2. 
6)        Manuela Tutolo, Enrico Ammirati, John Heesakkers, Thomas M. Kessler, Kenneth M. 
Peters, Tina Rashid, Karl-Dietrich Sievert, Michele Spinelli, Giacomo Novara, Frank Van der 
Aa, Dirk De Ridder,Efficacy and Safety of Sacral and Percutaneous Tibial Neuromodulation in 
Non-neurogenic Lower Urinary Tract Dysfunction and Chronic Pelvic Pain: A Systematic 
Review of the Literature,European Urology,Volume 73, Issue 3,2018,Pages 406-418,ISSN 
0302-2838, https://doi.org/10.1016/j.eururo.2017.11.002. 
7)        Nazan Tugay, PT, PhD, Türkan Akbayrak, PT, PhD, Funda Demirtürk, PT, PhD, İİ Ilkim 
Çıtak Karakaya, PT, PhD, Özge Kocaacar, PT, Umut Tugay, PT, PhD, Mehmet Gürhan 
Karakaya, PT, PhD, Fazlı Demirtürk, MD, Effectiveness of Transcutaneous Electrical Nerve 
Stimulation and Interferential Current in Primary Dysmenorrhea, Pain Medicine, Volume 8, 
Issue 4, May 2007, Pages 295–300, https://doi.org/10.1111/j.1526-4637.2007.00308.x 
8)         Thomas, M., Lundeberg, T., Björk, G., & Lundström-Lindstedt, V. (1995). Pain and 
discomfort in primary dysmenorrhea is reduced by preemptive acupuncture or low frequency 
TENS. European journal of physical medicine & rehabilitation, 5(3), 71-76. 
9)         Mira, Ticiana AA, et al. "Effectiveness of complementary pain treatment for women with 
deep endometriosis through Transcutaneous Electrical Nerve Stimulation (TENS): 
randomized controlled trial." European Journal of Obstetrics & Gynecology and Reproductive 
Biology 194 (2015): 1-6. 
10)    Johnson MI, Paley CA, Jones G, Mulvey MR, Wittkopf PG. Efficacy and safety of 
transcutaneous electrical nerve stimulation (TENS) for acute and chronic pain in adults: a 
systematic review and meta-analysis of 381 studies (the meta-TENS study). BMJ Open. 2022 
Feb 10;12(2):e051073. doi: 10.1136/bmjopen-2021-051073. PMID: 35144946. 
11)    Chen YJ, Zhou GY, Jin JH. Transcutaneous electrical acupoint stimulation combined with 
auricular acupoint sticking for treatment of primary nocturnal enuresis. Zhongguo Zhen Jiu. 
2010 May;30(5):371-4. 
12) 
 Tai C, Shen B, Chen M, Wang J, Liu H, Roppolo JR, de Groat WC. Suppression of 
bladder overactivity by activation of somatic afferent nerves in the foot. BJU Int. 2011 
Jan;107(2):303-9. 
13) 
Vance CG, Rakel BA, Blodgett NP, DeSantana JM, Amendola A, Zimmerman MB, 
Walsh DM, Sluka KA. Effects of transcutaneous electrical nerve stimulation on pain, pain 
sensitivity, and function in people with knee osteoarthritis: a randomized controlled trial. Phys 
Ther. 2012 Jul;92(7):898-910. 
14) 
 Robertson Val, Ward A, Low J, Reed A. Electrotherapy explained: principles and 
practice (4th edition). Elsevier Ltd (UK), 2006.   
15) 
Howe et al. Transcutaneous electric nerve stimulation (TENS) for the treatment of 
nocturnal enuresis in children. [NOT YET IN PRESS] 
16) 
Howe et al.  Optimal frequency used in transcutaneous electric nerve stimulation (TENS) 
for the treatment of nocturnal enuresis in children. [NOT YET IN PRESS] 
Barroso U Jr1, Viterbo W, Bittencourt J, Farias T, Lordêlo P. Posterior tibial nerve stimulation 
vs parasacral transcutaneous neuromodulation for overactive bladder in children. J Urol. 2013 
Aug;190(2):673-7. 

 
 
 
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Version Date: 5/14/2022 
 
 
 
 
 
 
 
J. APPENDIX 
 
VISUAL ANALOGUE SCALES 
 
 
Please rate your pelvic pain: 
Last 7 Days:      
No Pain = 0  1  2  3  4  5  6  7  8  9  10  = 
Max Pain 
Pain Right Now:    
No Pain = 0  1  2  3  4  5  6  7  8  9  10  = 
Max Pain 
Best this Week:     
No Pain = 0  1  2  3  4  5  6  7  8  9  10  = 
Max Pain 
Worst Day this Week:  
No Pain = 0  1  2  3  4  5  6  7  8  9  10  = 
Max Pain 
 
 
 
GUPI FEMALE 
 
Pain or Discomfort 
1.  In the last week, have you experienced any pain or discomfort in the following areas? 
a.  Entrance to vagina 
1  Yes 
0  No 
b.  Vagina 
1  Yes 
0  No 
c.  Urethra 
1  Yes 
0   No 
d.  Below your waist, in your pubic or bladder area 
1  Yes 
0  No 
 
2.  In the last week, have you experienced: 
a.  Pain or burning during urination? 
1  Yes 
0  No 
b.  Pain or discomfort during or after sexual intercourse? 
1  Yes 
0  No 
c.  Pain or discomfort as your bladder fills? 
1  Yes 
0  No 
d.  Pain or discomfort relieved by voiding? 
1  Yes 
0  No 
 
3.  How often have you had pain or discomfort in any of these areas over the last week? 
0 Never 
1 Rarely 
2 Sometimes 
3 Often 
4 Usually 
5 Always 
 
4.  Which number best describes your AVERAGE pain or discomfort on the days you had 
it, over the last week? 
 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
7 
 
8 
 
9 
 
10 
Name: ______________________ 
 
Date: _________________ 

 
 
 
 ------------------------------------------------------------------------------------------------------------------------------------------  
 
Version Date: 5/14/2022 
 
No 
Pain 
Pain as bad as you 
can imagine 
 
Urination 
5.  How often have you had a sensation of not emptying your bladder completely after you 
finished urinating, over the last week? 
0 Not at all 
1 Less than 1 
time in 5 
2 Less than half 
the time 
3 About 
half the time 
4 More than 
half the time 
5 Almost 
always 
 
6.  How often have you had to urinate again less than two hours after you finished urinating, 
over the last week? 
0 Not at all 
1 Less than 1 
time in 5 
2 Less than half 
the time 
3 About 
half the time 
4 More than 
half the time 
5 Almost 
always 
 
Quality of Life 
7.  How much have your symptoms kept you from doing the kinds of things you would usually 
do, over the last week? 
0 None 
1 Only a little 
2 Some 
3 A lot 
 
8.  How much did you think about your symptoms, over the last week? 
0 None 
1 Only a little 
2 Some 
3 A lot 
 
9.  If you were to spend the rest of your life with your symptoms just the 
way they have been during the last week, how would you feel about that? 
 
0 Delighted 
1  Pleased 
2  Mostly satisfied 
3  Mixed (about equally satisfied 
and dissatisfied) 
4  Mostly dissatisfied 
5  Unhappy 
6  Terrible 
 
  
 
 
 
 
 
 
 
 
 
 
GUPI Male 
 
 
Pain or Discomfort 
1.  In the last week, have you experienced any pain or discomfort in the following areas? 
Scoring 
Pain subscale:  Total of items 1a, 1b, 1c, 1d,  
2a, 2b, 2c, 2d, 3, and 4 
 
 
= _________  
Urinary subscale: Total of items 5 and 6 
= _________  
QOL Impact:  Total of items 7, 8, and 9 
= _________  
Total score: Sum of subscale scores  
= _________  
Name: ______________________ 
 
Date: _________________ 

 
 
 
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Version Date: 5/14/2022 
 
a.  Area between rectum and testicles (perineum) 
1  Yes 
0  No 
b.  Testicles 
1  Yes 
0  No 
c.  Tip of penis (not related to urination) 
1  Yes 
0   No 
d.  Below your waist, in your pubic or bladder area 
1  Yes 
0  No 
 
2.  In the last week, have you experienced: 
a.  Pain or burning during urination? 
1  Yes 
0  No 
b.  Pain or discomfort during or after sexual climax (ejaculation)? 
1  Yes 
0  No 
c.  Pain or discomfort as your bladder fills? 
1  Yes 
0  No 
d.  Pain or discomfort relieved by voiding? 
1  Yes 
0  No 
 
3.  How often have you had pain or discomfort in any of these areas over the last week? 
0 Never 
1 Rarely 
2 Sometimes 
3 Often 
4 Usually 
5 Always 
 
4.  Which number best describes your AVERAGE pain or discomfort on the days you had 
it, over the last week? 
 
0 
No 
Pain 
 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
7 
 
8 
 
9 
 
10 
Pain as bad as you 
can imagine 
 
Urination 
5.  How often have you had a sensation of not emptying your bladder completely after you 
finished urinating, over the last week? 
0 Not at all 
1 Less than 1 
time in 5 
2 Less than half 
the time 
3 About 
half the time 
4 More than 
half the time 
5 Almost 
always 
 
6.  How often have you had to urinate again less than two hours after you finished urinating, 
over the last week? 
0 Not at all 
1 Less than 1 
time in 5 
2 Less than half 
the time 
3 About 
half the time 
4 More than 
half the time 
5 Almost 
always 
 
Quality of Life 
7.  How much have your symptoms kept you from doing the kinds of things you would usually 
do, over the last week? 
0 None 
1 Only a little 
2 Some 
3 A lot 
 
8.  How much did you think about your symptoms, over the last week? 
0 None 
1 Only a little 
2 Some 
3 A lot 
 
9.  If you were to spend the rest of your life with your symptoms just the 
way they have been during the last week, how would you feel about that? 
 
0 Delighted 
1  Pleased 
2  Mostly satisfied 
3  Mixed (about equally satisfied and 
dissatisfied) 
4  Mostly dissatisfied 
5  Unhappy 
6  Terrible 

 
 
 
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Version Date: 5/14/2022 
 
 
 
 
 
 
 
 
 
 
 
 
Usage Chart Week 3-4, Month 1 
 
Day 
Monday 
Tuesday 
Wednesday Thursday 
Friday  
Saturday 
Sunday 
Used 
(Y/N) 
 
 
 
 
 
 
 
Duration 
(Minutes) 
 
 
 
 
 
 
 
 
Usage Chart Extension Month 1,2,3 
Date 
Range 
No 
Use 
Use 
(Minutes) 
Patch 
location 
Hertz 
(frequency, 
2-150 
cycles per 
second) 
Pulse 
Width 
(30-
260) 
Mode 
(N, 
B, 
M) 
Intensity 
(1-8) 
Pain 
level at 
edn of 
session 
(1-10) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Scoring 
Pain subscale:  Total of items 1a, 1b, 1c, 1d,  
2a, 2b, 2c, 2d, 3, and 4 
 
 
= _________  
Urinary subscale: Total of items 5 and 6 
= _________  
QOL Impact:  Total of items 7, 8, and 9 
= _________  
Total score: Sum of subscale scores  
= _________