Dyspareunia and Central Sensitization
Condition: Endometriosis; Central Sensitisation; Dyspareunia
MeSH terms: Endometriosis; Dyspareunia
Study type: Observational

Summary: 
      Background: Endometriosis affects 10% of reproductive aged females, and can have a negative
      impact on sexual quality of life. Endometriosis can cause pelvic pain with deep penetration
      during intercourse, as well as other sexual and non-sexual pains. This study will allow us to
      determine if an increase in sexual pain is related to central sensitization.

      Purpose: The purpose of this study is to determine if there is an association between the
      severity of sexual pain and central sensitization in women with endometriosis.

      Measurement tools: Data will be collected from the Clinic's Data Registry, an online
      questionnaire, a quantitative sensory test (QST) to measure pain-pressure threshold (PPT) as
      a marker of central sensitization, and daily entry to an online survey.

      Primary Hypothesis: Central sensitization (measured by lower pain-pressure threshold) will be
      associated with an increased severity of deep dyspareunia, as well as a tenderness of the
      bladder/pelvic floor and depression, in women with endometriosis.
    

Detailed description: 
      Background:

      Endometriosis results from the presence of endometrial cells growing abnormally outside the
      uterus and affects approximately 10% of reproductive-aged females. Endometriosis can be
      associated with various types of pain such as: dysmenorrhea (painful cramps with menses),
      deep dyspareunia (pelvic pain with deep penetration during intercourse), dyschezia (painful
      bowel movements) and chronic pelvic pain. Few studies have explored the association between
      endometriosis and deep dyspareunia resulting in a limited understanding of how to treat deep
      dyspareunia. Deep dyspareunia is defined as pelvic pain with deep penetration and occurs in
      50% of women with endometriosis at some time in their sexual lives. Deep dyspareunia has been
      shown to lower or cease intercourse, thus lowering self-esteem and resulting in negative
      effects on sexual functioning and interpersonal relationships.

      A potential contributor to deep dyspareunia in women with endometriosis that is largely
      under-researched is the concept of central sensitization. Central sensitization is an
      amplification of nociceptive signaling that may result from prolonged pain causing
      sensitization of the dorsal horn neurons, which results in hyperalgesia (increased response
      to pain) and allodynia (response to pain when there normally would not be). A recent study,
      comparing cross-sectional data from suspected or surgically diagnosed endometriosis patients,
      suggested that bladder and pelvic floor tenderness may be markers of central sensitization.
      However, the linkage between the indirect markers of central sensitization and the presence
      of central sensitization requires confirmation. This link can be assessed through validated
      quantitative sensory testing (QST). Likewise, the association between central sensitization
      and deep dyspareunia may also be confirmed through QST. QST is an objective measurement tool
      to determine the presence and/or degree of sensory disturbances, by detecting the alterations
      in nociceptive pathways. For example, a low pain-pressure threshold (i.e., increased pain
      sensation) at healthy unaffected areas, as measured by QST, indicates central sensitization.

      Purpose: To determine if deep dyspareunia is associated with central sensitization in women
      with endometriosis.

      Research Question: Is deep dyspareunia associated with central sensitization assessed by
      decreased pain-pressure threshold?

      Objectives:

      Primary Objective:

        1. Examine the association between central sensitization and severity of deep dyspareunia.

      Secondary Objectives:

        1. Examine the association between central sensitization and severity of non-sexual pains
           and Endometriosis Health Profile (EHP-30) scores.

        2. Examine the association between central sensitization and tenderness of the bladder and
           pelvic floor (determined by physician on physical exam).

        3. Examine the association between central sensitization and psychological measures
           (assessed by validated questionnaires).

           Research Hypotheses:

           Primary Hypothesis: Central sensitization (measured by pain-pressure threshold) is
           associated with an increased severity of deep dyspareunia, as well as a tenderness of
           the bladder/pelvic floor and depression, in women with endometriosis.

           Secondary Hypothesis: Women with endometriosis will have greater central sensitization
           (indicated by a lower pain-pressure threshold) than women without endometriosis.

           Setting: The Pelvic Pain and Endometriosis program at the BC Women's Health Centre uses
           an interdisciplinary approach to managing pain, including: physiotherapy for bladder and
           pelvic floor, surgical intervention, pain education and medical management. This program
           addresses multiple factors influencing pain through multiple approaches, as opposed to
           the traditional approach of surgical removal of the endometriosis to resolve the pain
           alone.

           Design: This study is a longitudinal, prospective cohort study, involving cases and
           controls.

           Primary Outcome: Severity of deep dyspareunia (0-10 numeric rating scale)

           Secondary Outcomes: Severity of superficial dyspareunia, severity of non-sexual pains,
           and psychological questionnaire scores

           Main Independent Variables: Central sensitization measured by pain-pressure threshold
           (PPT) determined through QST

           Study Population: The case population includes women who have consented to the Data
           Registry (H16-00264) and who are newly or re-referred to the BC Women's Centre for
           Pelvic Pain and Endometriosis, and who have regardless of the severity of deep
           dyspareunia, either: 1) previous surgical diagnosis of endometriosis or 2) current
           ovarian endometrioma cyst or 3) current endometriosis nodule.

           Sample Size: 30 cases and 15 controls.

           Recruitment and Data Collection prior to Test date:

           Cases:

           • At the end of their appointment with one of the endometriosis specialists at the BC
           Women's Centre for Pelvic Pain and Endometriosis, the physician will ask the patient if
           they are interested in learning more about this research study (if the physician deems
           them acceptable to be included based on screening of inclusion and exclusion criteria),
           and if so, will tell them a research assistant may call them.

           • A poster introducing the study will also be available in the clinic waiting rooms.

           • During a phone conversation, research team will remind the potential case participant
           that they have consented to the data registry, and consent to this study allows us
           access to analyze their data registry data. Verbal consent will be given if the
           potential case participant would like to participate, and a test appointment will be
           booked.

           • Case participants will sign the consent form in-person at the beginning of the test
           day appointment.

           Control:

           • Recruitment of the control group will be done by poster advertisement, as well as an
           in-person information session at the BC Women's Hospital. If they are interested in the
           study, potential participants will be asked to contact the research team to learn more
           about the study.

           • Research team will provide the potential control participant with a copy of the
           consent form (in person or by email). Each potential control participant will be advised
           to carefully read the consent form, and to contact the research team with any questions
           about the information contained in the consent form.

           • If the control participant expresses interest in the study after reading the consent
           form, a link to access the screening questions will be sent to them.

           • Criteria will be assessed by screening questions. If the participants are eligible
           based on the screening questions then they will be asked if they would like to consent
           to the study (online consent). This online consent allows access to the data from the
           screening questions. If they are not eligible, or do not consent to the study their
           screening questions will not be analyzed. If the control participant consents online
           they will be asked to complete additional questions (height, etc.).

           • Research team will receive an email once the control participant has consented online,
           and will contact the participant to book an appointment.

           • On the test day, the consent participants will sign the same consent form in-person to
           consent to the testing procedures.

           Procedures for Data Collection (on Test day)

           Questionnaire:

           Case and Control:

           • An online questionnaire will collect data such as: score of sexual and non-sexual
           pains, first day of last menstrual period,etc. The pelvic pain questions asked on this
           online questionnaire are modified from the Brief Pain Inventory Short Form. This
           questionnaire will be filled out online during the test appointment.

           Quantitative Sensory Testing (QST):

           Case and Control:

             -  After the questionnaire has been completed, the participants will undergo QST to
                measure their pressure-pain threshold (PPT), the point where the sensation of
                pressure has changed to the sensation of pain. Before testing begins, it will be
                made clear that the participants can withdraw from the study even during the
                procedure if they find it too uncomfortable.

             -  The PPT data will be written down on a paper copy with the unique study ID, and
                entered into an encrypted excel file.

             -  The observation made by this QST is that a lower PPT is suggestive of increased
                central sensitization.

           Feedback Questionnaire:

           Case and Controls:

           • After the participant's PPT has been measured, they will be given an anonymous
           feedback form to assess the procedure mechanisms and specifications, as well as comfort
           level before, during and after testing. This will allow investigators to adjust any
           necessary procedure details to create a more comfortable environment/test for future
           participants.

           Procedures for Data Collection (after Test day)

           Online Survey:

           Cases only:

             -  Case participants will be asked to record study data daily for six weeks after
                their scheduled test date.

             -  The data collected, will allow for daily prospective pain scores, rather than
                retrospective recollections of pain scores.

           Participants without email addresses will have the opportunity to complete the surveys
           on a printed out copy (given to them on the appointment day) and mail/bring in-person to
           the Centre at the end of the 6 weeks.
    

Intervention name(s): No Intervention
Intervention type(s): Other
Intervention description(s): There is no treatment intervention. We are assigning measurement tools such as the Electronic Thimble Algometer for QST and questionnaires to both groups.
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Tertiary care centre (BC Women's Health Centre for Pelvic Pain and Endometriosis) for case
        participants.

        Community sample for control participants.
      
Keywords: Quantitative sensory test (QST); Deep dyspareunia; Electronic Thimble Algometer