What is the Nature of Pelvic Floor Muscle Involvement in Dyspareunia?

Dyspareunia, or pain experienced by women during penetrative sexual activities, affects the psychological and sexual health of more than one in five Canadian women [1], yet its pathophysiology is poorly understood [2-4] and evidence for management approaches is limited.[5] It is thought that pelvic floor muscle (PFM) dysfunction is implicated in many forms of dyspareunia, while the nature and aetiology of this involvement remain largely unknown. The goal of this study is to understand if and how PFM dysfunction contributes to the pain experienced by women with provoked vestibulodynia (PVD), the most common cause of dyspareunia. This goal will be achieved through implementing an innovative and comprehensive approach to measuring the neuromuscular function of the PFMs. Understanding the pathophysiology of PVD is essential to the development of effective interventions to improve the health and quality of life of the many Canadian women who suffer from dyspareunia.

Study Overview

• Status: Completed
• Conditions: Dyspareunia
• Intervention / Treatment: Diagnostic test: Corticomotor excitability to the pelvic floor muscles; Diagnostic test: Pelvic floor muscle response to pressure applied at the vulvar vestibule; Diagnostic test: Pressure pain threshold (PPS); Diagnostic test: Temporal summation of pain; Diagnostic test: Tonic, phasic and reflex activation of the pelvic floor muscles (PFMs)

Detailed Description

Despite its high prevalence, little is known about the aetiology of dyspareunia. Dyspareunia is often sub-classified by the location (generalized vs a specific region) and by the stimulus that induces pain (provoked vs spontaneous). As such, PVD is characterized by severe sharp and/or burning pain felt at the entrance to the vagina (i.e. the vulvar vestibule) when pressure is applied to this area (i.e. provoked). [2] PVD is considered to be the most common cause of dyspareunia in pre-menopausal women, with a prevalence of about 12% of women, [1] while it remains underreported due to stigma embarrassment and shame. [6] Among women who seek intervention for PVD, involuntary PFM activation is thought to play a significant role in the onset and/or maintenance of pain. [7-15] Indeed, PVD is sometimes accompanied by intense, involuntary contraction of the PFMs [3], termed vaginismus (VAG). Yet it is not known whether PVD and VAG are distinct entities, or whether VAG exists along some continuum of PVD severity; [8,16] a matter of much debate in the literature.[17,19]

There is evidence to suggest that PFM dysfunction is a feature of PVD even in the absence of VAG.[7-15,20] When assessed through intravaginal palpation, women with PVD (without VAG) present with higher PFM tone (i.e., greater resistance to a passive manual stretch of the PFMs), difficulty relaxing their PFMs following a contraction, and lower PFM strength when compared to asymptomatic women.[7-9] Yet strength and tone graded by palpation are subjective, and studies were performed without assessor blinding. Some of these palpation findings have been corroborated using electromyography (EMG), including higher than normal tonic PFM activation,[14,21,22] poor ability to achieve a PFM contraction [10], impaired ability to relax the PFMs after activation [4], and/or poor ability to sustain a consistent activation level on voluntary PFM contraction,[10,15,23] yet the latter findings have been refuted by others.[9,20,24-26] While this more objective evidence exists, studies on PFM involvement in PVD using EMG have been small (n<12), have carried high risk of bias, [27] and authors have often failed to report whether women with PVD had concurrent VAG, perpetuating the lack of clarity around diagnosis.

Indeed, it is often difficult to determine on clinical examination whether or not VAG is present in women with PVD [3] and the new Diagnostic and Statistical Manual of Mental Disorders (DSM-5) omits any distinction between PVD and VAG, referring to both as genito pelvic pain penetration disorder (GPPPD17,21). Yet PFM involvement in PVD that is accompanied by VAG (PVD+VAG) may be distinct from PFM dysfunction in PVD with no concurrent VAG. [4,27-31] While trying to understand the nature of PFM involvement in PVD, it remains prudent to evaluate the PFMs while distinguishing between those with PVD+VAG and those with PVD alone.[19] This study will contribute to our knowledge of the nature of PFM involvement in PVD, and will inform on differences in PFM involvement between those with PVD alone and those with PVD+VAG.

Objectives and hypotheses: The overall goal of this project is to determine whether alterations in tonic, voluntary, reflex or behavioural responses of the superficial and/or the deep layer of the (PFMs) are implicated in PVD and/or PVD+VAG. There are four main aims with associated hypotheses:

Aim 1: To measure and compare pressure pain threshold (PPT), Temporal Summation (TS) at the vulvar vestibule, pain reported during the tampon test, and sexual function.

Hypothesis 1 (a): Compared to pain-free controls, women with PVD and PVD+VAG will demonstrate (a) greater self-reported pain during the tampon test. (b) lower PPT, (c) higher TS, and (d) lower sexual function.

Aim 2: To measure corticomotor excitability of projections to the PFMs through motor evoked potentials (MEPs) and cortically mediated silent periods (cSPs).

Hypothesis 2(a) Compared to pain-free controls, women with PVD and PVD+VAG will have larger MEPs and shorter cSPs in the bulbocavernosus, pubovisceral, and external anal sphincter muscles in response to transcranial magnetic stimulation (TMS) of the cortical area corresponding to the PFMs.

Hypothesis 2(b) Differences will be evident between women with PVD and PVD+VAG.

Aim 3: To measure the amplitude and timing of EMG responses to pressure applied to the vulvar vestibule and the posterior thigh Hypothesis 3 (a): Compared to pain-free controls, women with PVD and PVD+VAG will have higher incidences of anticipatory responses (ie. responses recorded before pressure is applied) recorded from the PFMs (bulbocavernosus, pubovisceral, external anal sphincter) and remote (uppper trapezius, hip adductor) muscles when standardized pressure stimuli are applied to the posterior vaginal fourchette regardless of the intensity of the pressure (low vs moderate).

Hypothesis 3 (b): Compared to pain-free controls, women with PVD and PVD+VAG will have higher muscle activation amplitude responses in the PFMs (bulbocavernosus, pubovisceral, external anal sphincter) and in more remote muscles (trapezius and hip adductor muscles) after standardized pressure stimuli (both low and moderate) are applied to the posterior vaginal fourchette.

Hypothesis 3 (c): Compared to pain-free controls, women with PVD and PVD+VAG will demonstrate larger responses in the PFMs (bulbocavernosus, pubovisceral, external anal sphincter) and in more remote muscles (trapezius or hip adductors) in response to pressure that is applied to the posterior thigh.

Aim 4: To measure the amplitude of PFM activation at rest (tonic), during maximum effort voluntary contraction of the PFMs and during a straining (Valsalva) maneuver Hypothesis 4: Compared to pain-free controls, women with PVD and PVD+VAG will demonstrate (a) higher tonic PFM activation, (b) more PFM activation during straining efforts (dyssynergia) and (c) lower PFM activation on maximum voluntary contraction.

Novelty and Contributions to the advancement of knowledge: Through this study, a comprehensive picture of neuromuscular impairments in the PFMs that are associated with PVD will be generated. Through Aim 1 it is expected to find in women with PVD and PVD+VAG, greater self reported pain during tampon test, lower pressure pain threshold, higher temporal summation and lower sexual function comparing with the control group. No study has investigated corticomotor excitability of projections to the PFMs through TMS. Through Aim 2 differences in corticomotor excitability to the PFMs, evidenced through higher amplitude MEPs and shorter duration cSPs are expected to be found, between women with and without PVD as well as differences in the extent of enhanced corticomotor excitability to the PFMs between PVD and PVD+VAG. Also no study has evaluated whether differences seen in tonic or phasic responses of the PFMs between women with PVD and controls are present because of or in anticipation of pain. Studies by Van Lunsen & Ramakers [32], Reissing et al. [8] and van der Velde & Everaerd [33] suggest that the PFMs respond to generalized anxiety and in response to watching sexually threatening scenes. It is quite possible, and even probable, that anxiety or fear of pain may influence study outcomes [4,34]. Through Aim 3, the timing and magnitude of PFM activation will be evaluated to determine whether responses occur in anticipation of (i.e. before) and/or in response to pressure stimuli delivered at the vulvar vestibule. The hypotheses under Aims 2 and 3 have never before been tested and doing so will have a significant impact on our understanding of the pathophysiology of PVD. Through Aim 4, it we expect to corroborate previous findings in the literature: that women with PVD and PVD+VAG will demonstrate higher tonic PFM activation and PFM dyssynergia during straining - both being functionally related to increased corticomotor excitability.

If women with PVD+VAG exhibit higher corticomotor excitability than women with PVD alone, this finding will be a major step toward understanding PVD and PVD+VAG as separate conditions, and will set the stage for improved diagnoses and targeted treatments such as repetitive TMS35 and neurotropic medications.[36] Further, interventions that have shown some evidence for effectiveness [37] including stretching, [9,38,39] acupuncture, [40] Botox injection, [41,42] and cognitive behavioural therapy [39] may be enhanced by combining them with new interventions that focus on corticomotor inhibition. The impact of any new as well as existing interventions on corticomotor excitability can, in turn, be evaluated using the innovative yet accessible assessment approaches developed through this work.

For descriptive purposes, five on-line questionnaires will be applied to assess sexual function [43,44], pain [45] pain catastrophising [46], depression/anxiety [47,48], and central sensitization [49].

Assessment will be scheduled within the week following the start of women's last menstrual cycle to account for cyclic variations in motor and sensory thresholds [50] , and at a time that is convenient.

• Study Type: Observational
• Enrollment (Actual): 85

Contacts and Locations

• Study Contact: Name: Flavia Antonio; Phone Number: 4102 613-562-5800; Email: fignacio@uottawa.ca
• Study Contact Backup: Name: Linda McLean; Phone Number: 4102 613-562-5800; Email: linda.mclean@uottawa.ca

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1N 6N5
      • Flavia Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Females with PVD alone or PVD+ VAG will be recruited at the vulvar pain clinic at The Ottawa Hospital and from local physiotherapy clinics that cater to females with pelvic floor dysfunction.

Control participants will be recruited from the local community through advertisements, word of mouth and social media.

Description

Inclusion Criteria:

• Premenopausal women over the age of 18
• Biologically born female
• Signs and symptoms consistent with Provoked Vestibulodynia (PVD) alone or PVD+ Vaginismus (VAG) (i.e. evidence of a vaginal muscle spasm in response to palpation) or no history of pain during sexual activities or tampon insertion to serve as a comparison group
• Not currently pregnant, or pregnant in the past six months.

Exclusion Criteria:

• Neurological condition such as stroke, multiple sclerosis, spinal cord injury, epilepsy, or history of epilepsy in the family, etc
• Metal implants (cochlear, pacemaker, etc.)
• Tendency to faint
• in Peri- or post-menopause
• express high levels of anxiety about the assessment protocol

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Provoked vestibulodynia (PVD); Provoked vestibulodynia (PVD) is characterized by severe sharp and/or burning pain felt at the entrance to the vagina (i.e. the vulvar vestibule) when pressure is applied to this area or during attempts at vaginal insertional activities (i.e. provoked).	Diagnostic test: Corticomotor excitability to the pelvic floor muscles; Transcranial magenetic stimulation will be used to probe the excitability of cortical projections to the pelvic floor muscles. The outcomes of interest will include motor evoked potential amplitude and silent period.; Diagnostic test: Pelvic floor muscle response to pressure applied at the vulvar vestibule; Electromyography will be used to determine whether the pelvic floor muscles (PFMs) respond to pressure applied to the vulvar vestibule as anticipatory (i.e. PFMs are active before the pressure is applied) and as behavioural (i.e. PFMs are active after the pressure is applied) responses. The amplitude of the EMG responses will also be recorded.; Diagnostic test: Pressure pain threshold (PPS); A custom vulvalgesiometer will be used to determine the mean pressure at which participants first report pain at the posterior vaginal fourchette.; Diagnostic test: Temporal summation of pain; A custom vulvalgesiometer will be used to apply the same pressure (rated as 4/10 duiring PPS testing as described above) to the vulvar vestibule across 10 repetitions. The difference in pain rated on the tenth application and that rated on the first application will be the outcome.; Diagnostic test: Tonic, phasic and reflex activation of the pelvic floor muscles (PFMs); Electromyography will be used to measure the mean smoothed, rectified activation amplitude across 1 second of complete rest, across three maximal effort PFM contractions, and across three attempts at a bearing down maneuver.
Provoked vestibulodynia (PVD) + Vaginismus (VAG); PVD is sometimes accompanied by intense, involuntary contraction of the PFMs3, termed vaginismus (VAG).	Diagnostic test: Corticomotor excitability to the pelvic floor muscles; Transcranial magenetic stimulation will be used to probe the excitability of cortical projections to the pelvic floor muscles. The outcomes of interest will include motor evoked potential amplitude and silent period.; Diagnostic test: Pelvic floor muscle response to pressure applied at the vulvar vestibule; Electromyography will be used to determine whether the pelvic floor muscles (PFMs) respond to pressure applied to the vulvar vestibule as anticipatory (i.e. PFMs are active before the pressure is applied) and as behavioural (i.e. PFMs are active after the pressure is applied) responses. The amplitude of the EMG responses will also be recorded.; Diagnostic test: Pressure pain threshold (PPS); A custom vulvalgesiometer will be used to determine the mean pressure at which participants first report pain at the posterior vaginal fourchette.; Diagnostic test: Temporal summation of pain; A custom vulvalgesiometer will be used to apply the same pressure (rated as 4/10 duiring PPS testing as described above) to the vulvar vestibule across 10 repetitions. The difference in pain rated on the tenth application and that rated on the first application will be the outcome.; Diagnostic test: Tonic, phasic and reflex activation of the pelvic floor muscles (PFMs); Electromyography will be used to measure the mean smoothed, rectified activation amplitude across 1 second of complete rest, across three maximal effort PFM contractions, and across three attempts at a bearing down maneuver.
Control; Participants matched by age (within 2 years), parity (parous vs nulliparous) and use of oral contraceptive medications (yes vs no) to women in the PVD group, with no signs and symptoms of PVD.	Diagnostic test: Corticomotor excitability to the pelvic floor muscles; Transcranial magenetic stimulation will be used to probe the excitability of cortical projections to the pelvic floor muscles. The outcomes of interest will include motor evoked potential amplitude and silent period.; Diagnostic test: Pelvic floor muscle response to pressure applied at the vulvar vestibule; Electromyography will be used to determine whether the pelvic floor muscles (PFMs) respond to pressure applied to the vulvar vestibule as anticipatory (i.e. PFMs are active before the pressure is applied) and as behavioural (i.e. PFMs are active after the pressure is applied) responses. The amplitude of the EMG responses will also be recorded.; Diagnostic test: Pressure pain threshold (PPS); A custom vulvalgesiometer will be used to determine the mean pressure at which participants first report pain at the posterior vaginal fourchette.; Diagnostic test: Temporal summation of pain; A custom vulvalgesiometer will be used to apply the same pressure (rated as 4/10 duiring PPS testing as described above) to the vulvar vestibule across 10 repetitions. The difference in pain rated on the tenth application and that rated on the first application will be the outcome.; Diagnostic test: Tonic, phasic and reflex activation of the pelvic floor muscles (PFMs); Electromyography will be used to measure the mean smoothed, rectified activation amplitude across 1 second of complete rest, across three maximal effort PFM contractions, and across three attempts at a bearing down maneuver.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Motor evoked potential (MEP) peak to peak amplitude (µV)	Transcranial magnetic stimulation outcome (i.e. Motor evoked potential peak to peak amplitude - µV) will be determined for all participants and compared among groups. A Magstim® 200 system coupled with a double cone coil (96 mm loops, P/N 9902) [57] will be used to probe the corticospinal projections to PFMs. MEPs will be ensemble averaged to generate estimates of MEP peak to peak amplitude (µV).	1 day
Cortical silent period duration (ms)	Transcranial magnetic stimulation outcome (i.e. cortical silent period duration - ms) will be determined for all participants and compared among groups. A Magstim® 200 system coupled with a double cone coil (96 mm loops, P/N 9902) [57] will be used to probe the corticospinal projections to PFMs. MEP cortical silent period (cSP) will be measured from individual trials and then averaged.	1 day
Anticipatory responses (ms)	The proportion of women in each group who demonstrate anticipatory responses of the PFMs to impending pressure applied at the vulvar vestibule will be determined for each group. Participants will be deemed to have anticipatory responses if electromyographic signals recorded from the PFMs precede the application of pressure. A vulvalgesiometer [58] will be employed using a response-dependent methodology. [59,60] The vulvalgesiometer will be used to apply low (25 g) and moderate (232 g) pressures to the posterior vaginal fourchette or to the posterior thigh, the moderate value having been generated through the team's previous research. [9]	1 day
Behavioural responses (µV)	The proportion of women in each group who demonstrate behavioral responses of the PFMs to pressure applied at the vulvar vestibule will be determined for each group. Participants will be deemed to have behavioural if the activation of the PFMs (or other muscles) occurs after the pressure is applied. A vulvalgesiometer [58] will be employed using a response-dependent methodology. [59,60] The vulvalgesiometer will be used to apply low (25 g) and moderate (232 g) pressures to the posterior vaginal fourchette or to the posterior thigh, the moderate value having been generated through the team's previous research. [9]	1 day
Tonic, phasic and reflex activation of the pelvic floor muscles	Surface Electromyography (EMG) recorded using differential suction electrodes (DSEs, developed by Dr. McLean) [54-56] will be used to measure tonic, voluntary and reflex activation of the superficial and deep PFMs. Smoothed peak EMG amplitudes (µV) will be computed as outcomes while women keep their PFMs as relaxed as possible (tonic), contract as strongly as possible (phasic) and perform a straining maneuver (reflex activation).	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tampon test	Women will be instructed to insert and then remove the tampon and they will be instructed to record the degree of pain during the entire insertion/ removal experience on a 0-10 pain numeric rating scale, with 0 meaning no pain, and 10 meaning the worst possible pain.	1 day
Pressure pain threshold (PPT)	The pressure at which women report pain on pressure applied through a cotton swab to the region of the posterior vaginal fourchette. Pressure pain threshold (PPT) will be determined using a custom vulvalgesiometer. PPT will be defined as the average pressure at which women first report pain when the cotton swab tip of the vulvalgesiometer is applied at 6 o' clock of the vaginal introitus [51].	1 day
Temporal summation (TS) of pain	The difference in pain rating (scale 1-10) between the tenth and first application of a pressure applied to the posterior vaginal fourchette through a custom vulvalgesiometer. The PPT determined at the 6-o-clock position, will be applied ten times at a rate of approximately one per second at the 6 o'clock location on the vestibule. Participants will rate their pain level on the initial and final application of this pressure using a Numeric Rating Scale (0-10). TS will be defined as the difference in pain rating between the final and first application of the pressure [52,53]	1 day

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Female sexual function index (FSFI)	This is a 19-item validated questionnaire [43,44] for assessing the key dimension of sexual function in women, considered a gold standard for evaluation of sexual function. It assesses six domains: desire, arousal , lubrification, orgasm, satisfaction, and pain. All scores are totaled for a maximum of 36. Higher scores represents better sexual function. A score ≤26.55 has been set as a cutoff to identify those at risk for sexual dysfunction.	1 day
McGill Pain Questionnaire	This questionnaire consists primarily of 3 major classes of word descriptors - sensory, affective and evaluative - that are used by patients to specify subjective pain experience. It also contains an intensity scale and other items to determine the properties of pain experience. This questionnaire is composed of 78 words. Respondents choose those that best describe their experience of pain. Scores are tabulated by summing values associated with each word; scores range from 0 (no pain) to 78 (severe pain). Quantitative differences in pain may be reflected in respondents word choice.	1 day
Pain catastrophizing scale	The Pain Catastrophizing Scale is a reliable and valid measure of catastrophizing. The scores from this questionnaire is predictors of intensity of physical and emotional distress. It is a self-report measure, consisting of 13 items scored from 0 to 4, resulting in a total possible score of 52. The higher the score, the more catastrophizing thoughts are present	1 day
Depression Anxiety Stress Scale (DASS)	This is a 42-item self report instrument designed to measure the three related negative emotional states of depression, anxiety and tension/stress [47,48]. Each one contains 14 items, divided into subscales of 2-5 items with similar content. The DASS have been shown to have high internal consistency and to yield meaningful discriminations in a variety of settings. A higher score on the DASS indicates greater severity or frequency of these negative emotional symptoms. The maximum score is 126.	1 day
Central sensitization inventory	The Central Sensitisation Inventory (CSI) [49], is a self-report outcome measure designed to identify patients who have symptoms that may be related to central sensitisation (CS) or central sensitivity syndromes (CSS). Part A includes 25 questions related to common CSS symptoms. Part B determines if the patient has been diagnosed with certain CSS disorders or related disorders, such as anxiety and depression. CSI severity levels have been established for part A: subclinical = 0 to 29; mild = 30 to 39; moderate = 40 to 49; severe = 50 to 59; and extreme = 60 to 100.	1 day

Collaborators and Investigators

• Sponsor: University of Ottawa
• Investigators: Principal Investigator: Linda McLean, University of Ottawa

Publications and helpful links

General Publications

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• McLean L, Thibault-Gagnon S, Brooks K, Goldfinger C, Pukall C, Chamberlain S. Differences in Pelvic Morphology Between Women With and Without Provoked Vestibulodynia. J Sex Med. 2016 Jun;13(6):963-71. doi: 10.1016/j.jsxm.2016.04.066.
• Reissing ED, Binik YM, Khalife S, Cohen D, Amsel R. Vaginal spasm, pain, and behavior: an empirical investigation of the diagnosis of vaginismus. Arch Sex Behav. 2004 Feb;33(1):5-17. doi: 10.1023/B:ASEB.0000007458.32852.c8.
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Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2021
• Primary Completion (Actual): January 15, 2023
• Study Completion (Actual): March 20, 2023

Study Registration Dates

• First Submitted: January 10, 2020
• First Submitted That Met QC Criteria: January 15, 2020
• First Posted (Actual): January 21, 2020

Study Record Updates

• Last Update Posted (Actual): April 4, 2023
• Last Update Submitted That Met QC Criteria: March 31, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: electromyography; transcranial magnetic stimulation; dyspareunia; pressure pain threshold; provoked vestibulodynia; vaginismus; temporal summation
• Additional Relevant MeSH Terms: Mental Disorders; Sexual Dysfunctions, Psychological; Sexual Dysfunction, Physiological; Dyspareunia
• Other Study ID Numbers: H-11-18-1183

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Spreadsheets will be provided by email upon request and based on the planned use of the data.
• IPD Sharing Time Frame: Data will be available for 10 years after the publication of the study results.
• IPD Sharing Access Criteria: Planned use of data for systematic review.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No