What is the Nature of Pelvic Floor Muscle Involvement in Dyspareunia?
Condition: Dyspareunia
MeSH terms: Dyspareunia
Study type: Observational

Summary: 
      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.
    

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.
    

Intervention name(s): Corticomotor excitability to the pelvic floor muscles; Pelvic floor muscle response to pressure applied at the vulvar vestibule; Pressure pain threshold (PPS); Temporal summation of pain; Tonic, phasic and reflex activation of the pelvic floor muscles (PFMs)
Intervention type(s): Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test
Intervention description(s): 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.; 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.; A custom vulvalgesiometer will be used to determine the mean pressure at which participants first report pain at the posterior vaginal fourchette.; 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.; 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.
Observational model: Case-Control
Time perspective: Cross-Sectional
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.
      
Keywords: dyspareunia; electromyography; transcranial magnetic stimulation; pressure pain threshold; temporal summation; vaginismus; provoked vestibulodynia