Andrea Rapkin, MD, is Board Certified by the American College of Obstetricians and Gynecologists (of which she is also a fellow). After obtaining her MD, she completed her residency in OBGYN at UCLA then joined the faculty at UCLA and is a Professor of Obstetrics and Gynecology. She was one of the first Obstetrician-Gynecologists to adapt the multidisciplinary pain management approach to the evaluation and treatment of women with pelvic and vulvar pain.
You are the founder and director of a clinic focused on a multidisciplinary pain management approach to the evaluation and treatment of women with pelvic and vulvar pain. How did you identify such a clinic as a therapeutic need for patients?
Dr. Rapkin: The short answer is that a significant proportion of women were not experiencing pain relief or had incomplete relief with traditional medical or surgical therapy. At the time, we also identified various red flags for traditional treatment failures. These red flags included the following: pain of greater than 6 months duration, pain out of proportion to pathology found on examination, multiple visceral and somatic complaints, and psychosocial abnormalities. We now understand more about the neurobiology underpinning these red flags.
With the widespread availability of laparoscopy in the late 70s and early 80s, many studies investigated the relationship between endometriosis lesions and pain. The general consensus is that there is no relationship between the location or severity of the endometriosis lesions or the disease stage (American Society for Reproductive Medicine staging) with type of symptoms, symptom severity, treatment response, recurrence, or even prognosis. In fact, pain recurrence after adequate surgical treatment is unrelated to the presence of endometriosis lesions found at the time of repeat laparoscopy. This lack of association between pain and presence of visible disease was supported by a recent New England Journal of Medicine article by Zondervan and colleagues demonstrating that up to 30% of women with chronic pelvic pain, present after excision of endometriotic lesions, become unresponsive to conventional treatment.
The neurobiological responses in an individual with chronic pain are more complicated than those seen in the setting of acute pain. Chronic pain may be triggered or maintained by an inflammatory process such as endometriosis but, over time, altered neural processing and psychosocial maladaptation can occur. The altered processing consists of both peripheral and central sensitization which change the way sensory information from the pelvic viscera and surrounding somatic structures in the periphery is transmitted and interpreted in the central nervous system (spinal cord and brain). Visceral pelvic pain can emanate from the uterus, ovaries and fallopian tubes, the urinary bladder, and the bowel, while the somatic sources include the surrounding abdominal wall, low back and pelvic floor muscles, and fascia, and bones. Signal amplification or peripheral sensitization in the pelvic region in women with endometriosis starts with localized inflammation, neovascularization, invasion and innervation of endometriotic implants. As the pelvic organs share thoracolumbar and sacral autonomic neural pathways, inflammation or dysfunction in one organ or tissue, such as the uterus, over time can sensitize or lead to dysfunction in other pelvic organs, such as the bladder or bowel (called viscero-visceral cross sensitization). Finally, somatic structures sharing intervention with the pelvic viscera, such as the fascia and muscles of the lower abdomen, pelvic floor lower back also become sources of pain because of a process called viscero-somatic sensitization. Women who have endometriosis are therefore more likely to experience IBS, bladder pain syndrome/interstitial cystitis and vulvodynia, and up to 80% of individuals can develop myofascial pain related to trigger points and muscle dysfunction. Up to 50% of women with bladder pain have endometriosis. Those with endometriosis or bladder pain are 2.5 times more likely to also have IBS.
Over time, other visceral and somatic structures innervated by higher levels of the spinal cord can be affected, leading to more widespread pain. Central sensitization manifests as an amplification of pain in the spinal cord and brain. The presence of more than two chronic “unexplained” pain conditions, such as chronic pelvic pain, vulvodynia, myofascial pain, headache, etc suggest the presence of central sensitization. Anxiety, depression, and maladaptive coping strategies often ensue. Functional MRI studies have documented altered central processing in the brain in many chronic pain states including endometriosis. Interdisciplinary therapy including physical therapy, mental health, and pain management/anesthesiology is more effective compared with medical and or surgical therapy alone for endometriosis-related pain in the setting of peripheral and central sensitization.
What should clinicians look for, or what stands out to them, to confirm the endometriosis diagnosis when pain is the presenting symptom?
Dr. Rapkin: There are no pathognomonic symptoms or biomarkers for endometriosis; however, the following historical features have been shown to be linked with a greater likelihood of finding endometriosis:
- persistent dysmenorrhea (menstrual pain) despite NSAID and hormonal treatment
- cyclical pain that is premenstrual and menstrual that progresses to chronic pain or is accompanied by abnormal or heavy menstrual bleeding
- deep dyspareunia
- dyschezia (pain with bowel movements), and sometimes bloating.
An individual with menstrual pain since menarche can have up to a 5% increased risk of endometriosis. Endometriosis in a first-degree relative elevates the risk for endometriosis by 7% to 10%.
Given the complexity of chronic pain, it is important not to assume endometriosis is the only source of pain. All the pelvic visceral and somatic structures should be evaluated. A thorough history addresses all the patient’s symptoms, including vaginal, gastrointestinal and genitourinary. Aggravating factors such as menstrual cycle, bowel and bladder functioning, physical activity, sexual intercourse and stress should be queried. In addition, assessment of mood, anxiety or depression, sleep disturbance and effect of pain on daily functioning are relevant as is history of abuse or trauma (physical, sexual or emotional). This history can be lengthy, so a detailed pain questionnaire is helpful. (See the pelvicpain.org website for a user-friendly pain questionnaire).
With the previously mentioned risk factors in mind, and after a thorough history has been obtained, a pain-localizing exam should be conducted including the abdominal wall, pelvic floor, and then the bimanual and rectovaginal exams for the abdominal wall myofascial/neuropathic pain assessment for which Carnett’s test can be very useful—tender points on the abdominal wall are palpitated and the patient is asked to give a numerical rating of the pain (1-10/10) and marked with a pen. The patient is then asked to either perform a bilateral straight leg raise or an abdominal crunch, and the areas are re-palpitated. If the marked areas are more painful to palpation during the abdominal crunch or the bilateral straight leg raise, it suggests an abdominal wall pain (myofascial or neuropathic) or component of the pain. Similarly, pelvic floor muscles should be assessed after the abdominal wall exam is completed. This is best accomplished with a unit-digital exam with palpation of pelvic muscles for tenderness and hypertonia on exam. These myofascial findings are often present in the setting of endometriosis, but they can be primary-unrelated to presence or absence of endometriosis.
What are your focused disciplines for approaching endometriosis-associated pain? How do you recommend these clinicians or specialists come together to effectively manage a patient’s conditions?
Dr. Rapkin: The gynecologist or primary care provider can address the chronic inflammatory, estrogen-dependent aspect of endometriosis. Begin with nonsteroidal, anti-inflammatory medication and combined estrogen-progestin or high-dose progestin-alone hormonal therapy to lower estrogenic stimulation of lesions and decidualize those progestin-sensitive lesions. For menstrual cycle related pain (luteal periovulatory or menstrual phase) cyclical exacerbation of other chronic pain conditions, early intervention is recommended. Adequately dosed preemptive nonsteroidal inflammatory agents and, if not tolerated or effective, begin combined hormonal contraceptives or intrauterine or higher dose progestins menstrual suppression, with either continuous monophasic hormonal contraceptives or progestins, is very important for pain that is cyclical or exacerbated in a cyclical fashion. Progestins can be administered orally, such as norethindrone acetate; intramuscularly or subdermally (depot medroxyprogesterone acetate or etonogestrel implant); or intrauterine (which does not lower estrogen levels but can be therapeutic for suppression of menses and local treatment of endometriosis). Failure of hormonal therapy and management of other co-occurring pain conditions warrants trial of a second-line medical therapy such as gonadotropin-releasing hormone antagonist or agonist or surgery for definitive diagnosis and surgical ablation or excision of endometriosis lesions.
I would suggest that gynecologists who treat women with endometriosis and chronic pain try to build a team in their geographic area. Relevant specialists for an interdisciplinary approach include:
- Pelvic floor physical therapist to evaluate and address myofascial dysfunction and pain and voiding abnormalities, such as urinary urgency or frequency and constipation
- Gastroenterologist for evaluation and treatment of irritable bowel or functional abdominal pain and bloating syndrome or inflammatory bowel disease. Urologist or urogynecologist to assess and treat bladder pain syndrome/interstitial cystitis
- Primary care evaluation for diffuse myofascial pain, fibromyalgia, arthralgias, and other inflammatory conditions, and for management of headache and migraine. Rheumatology and neurology specialists may be needed
- Mental health providers for treatment of anxiety, depression, or PTSD and to address stress management, coping skills and provide cognitive behavioral therapy
- Interventional pain management specialist such as physical medicine and rehabilitation (PM and R), pain anesthiologist, neurologist or interventional radiologist to provide relevant nerve blocks, trigger point injections, or botulinum toxin injection.
- Gynecologists experienced in the management of chronic pelvic pain also provide nerve blocks, trigger point and botulinum toxin injections.