This chapter should be cited as follows:
Malhotra N, Sinha P, et al, Glob. libr. women's med.,
ISSN: 1756-2228; DOI 10.3843/GLOWM.418633

The Continuous Textbook of Women’s Medicine Series – Gynecology Module

Volume 4

Benign gynecology

Volume Editor: Professor Shilpa Nambiar, Prince Court Medical Centre, Kuala Lumpur, Malaysia

Chapter

The Evaluation and Treatment of Women with Pelvic Pain

First published: September 2024

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BRIEF OVERVIEW

Pelvic pain in women is defined as pain present in the pelvis or the bilateral lower quadrants of the abdomen. It can be acute or chronic. Acute pelvic pain in women is typically non-cyclic, sudden in onset, and present for less than 3 months.¹ Chronic pelvic pain (CPP) is generally defined as non-cyclic pain perceived to be in the pelvic area that has persisted for 3 to 6 months or longer and is unrelated to pregnancy. CPP is a symptom that can represent pathology in a somatic structure or viscera, central sensitization of pain, or both. In this chapter we focus on CPP with a brief overview of acute pelvic pain (Figure 1).

ACUTE PELVIC PAIN

Acute pelvic pain in women may be due to gynecological, gastrointestinal, and urinary tract disorders. Ectopic pregnancy (EP), pelvic inflammatory disease (PID), and ruptured ovarian cysts are the most common gynecological causes for acute pelvic pain and their diagnosis can be challenging. Acute pelvic pain is a common presentation in primary care. Although well-designed studies on the prevalence of pelvic pain are lacking, one study estimated that up to 39% of reproductive-aged women who presented to their primary care physician had symptoms related to pelvic pain, and one in seven women has acute or chronic pelvic pain at some point.^2,3 The consequence of a missed diagnosis can be serious. For example, delay in diagnosis of an ectopic pregnancy can result in rupture and life-threatening hemorrhage. Untreated sexually transmitted infections and PID can lead to long-term sequelae, such as infertility and chronic pain. The physical examination should focus on vital signs, abdominal examination, bimanual pelvic examination, and speculum examination. Hypotension, tachycardia, or evidence of guarding or rebound on abdominal examination could indicate a surgical emergency (e.g., ruptured ectopic pregnancy, ovarian torsion, ruptured appendix) and should prompt immediate referral.⁴ Laboratory tests and imaging studies are largely guided by history and physical examination findings to identify possible causes of pelvic pain. Pelvic ultrasonography, consisting of transabdominal combined with transvaginal ultrasonography, is usually the imaging modality of choice because of a lack of radiation exposure and high sensitivity.⁵ Currently, however, if acute appendicitis is suspected over gynecologic conditions (e.g., a non-pregnant woman with isolated right lower quadrant pain and nausea), or if ultrasonography does not clearly show a normal appendix, CT is still considered more accurate, with a sensitivity of 94–97% and specificity up to 100%.^6,7 CT use has led to a decrease in laparotomies performed for suspected appendicitis in which the final pathology was negative for acute appendicitis. CT is also appropriate to evaluate acute pelvic pain if ultrasonography is not readily available (Figure 2).

Therefore, a solid knowledge of the differential diagnosis of acute pelvic pain in women and a thorough history and physical examination will lead the practitioner to the underlying cause in the vast majority of cases. But all women who present with acute pelvic pain MUST have a pregnancy test as a part of their initial workup. If imaging is needed, pelvic ultrasound is an excellent tool and should be utilized first before CT and MRI in most cases.

CHRONIC PELVIC PAIN

Introduction

Chronic pelvic pain (CPP) refers to pain of 3–6 months' duration (or longer) that occurs below the umbilicus and is severe enough to cause functional disability or require treatment. CPP is defined by the European Association of Urology (EAU) as “chronic or persistent pain perceived in structures related to the pelvis of either men or women. It is often associated with negative cognitive, behavioral, sexual and emotional consequences as well as with symptoms suggestive of lower urinary tract, sexual, bowel, pelvic floor or gynecological dysfunction" (Figure 3).

In the case of documented nociceptive pain that becomes chronic/persistent through time, pain must have been continuous or recurrent for at least 6 months. If non-acute and central sensitization pain mechanisms are well documented, then the pain may be regarded as chronic, irrespective of the time period.⁸ The potential etiologies of CPP are diverse and can arise from pathology or dysfunction from any one of the multiple organ systems present in the pelvis. In addition, regardless of whether there is or is not identifiable anatomic pathology, CPP can also represent a centralized pain syndrome. CPP is generally considered to be a description of a clinical condition rather than a diagnosis. CPP has a significant impact on women of reproductive and non-reproductive age, with a considerable burden on overall quality of life (QoL) and on psychological, functional, and behavioral status.

Epidemiology and pathogenesis

The reported prevalence of CPP ranges from 4 to 16% in the general population, but only approximately one-third of women with CPP seek medical care.^9,10,11,12 The relative frequency reported for the various causes of CPP is significantly influenced by the local patient population, referral patterns, and specialty focus of the clinical practice. One population-based study reported that gastrointestinal and urologic problems were more common than gynecologic conditions in women with CPP; gynecologic conditions accounted for approximately 20% of cases of CPP in this population.¹²

Regardless of the initial source of pain, there is increasing awareness that persistence of pain, from any underlying etiology, is a risk factor for the development of a chronic pain syndrome as a result of central nervous system changes collectively referred to as central sensitization.^13,14 Research increasingly suggests an individual's genetic makeup, coupled with their individual sensory experience history, influences their relative pain output "set-point", analogous to how an audio speaker output is controlled by a volume knob.¹⁵ This relative output explains why some pathological processes or sensory experiences do not result in pain in one woman, but cause dramatic pain in others (e.g., acute labor pain, leiomyoma, or endometriosis). Further, problems in one organ can influence dysfunction in another organ, as evidenced by the high comorbidity of painful bladder syndrome, endometriosis, and irritable bowel syndrome with dysmenorrhea.^16,17 These and other mechanisms likely contribute to the enhanced sensitivity to pain and prolonged pain after sensation seen in women with CPP.

Etiology

CPP is an end symptom with multiple potential etiologies (Table 1). Although any one disorder may be the cause of CPP, chronic pain is often the end result of multiple overlapping pain conditions, with each contributing to the generation of pain, thus requiring management. It is important that the clinician begins with a thorough history and physical examination to identify all conditions that are contributing to pain and decreased quality of life. Patients should be counseled that the evaluation takes time, many etiologies are considered, treatment is not always curative, and consultation with other providers may be warranted.

While CPP is not the hallmark symptom of adenomyosis, leiomyoma, intra-abdominal adhesions, or PID, the high prevalence of these conditions among women with CPP makes them important considerations when evaluating women with CPP.

Common gynecological causes of chronic pelvic pain

Endometriosis

Endometriosis is the most common gynecologic cause of CPP and is the most common diagnosis made at the time of gynecologic laparoscopy for the evaluation of CPP.²⁰ It should be noted that the presence and severity of endometriosis does not consistently correlate with symptom severity except in the case of posterior cul-de-sac disease and severe dyspareunia. The coexistence of other pain syndromes in women and adolescents with endometriosis is higher than that in the general population.^21,22

Pelvic adhesions

The relationship between CPP and intra-abdominal adhesions is poorly defined. While most adhesions are often clinically silent, dense adhesions that limit organ mobility cause visceral pain and may account for pelvic pain based on pain mapping at the time of laparoscopy.^23,24 Contrary to this a meta-analysis also reported that, in general, patients with CPP and intra-abdominal adhesions did not benefit long term from adhesiolysis.²⁵

Adenomyosis

Adenomyosis is a disorder in which endometrial glands and stroma are present within the uterine musculature. The ectopic tissue induces hypertrophy and hyperplasia of the surrounding myometrium, leading to abnormal uterine bleeding and dysmenorrhea often reported in women with adenomyosis. Endometriosis and adenomyosis are believed to be associated. Adenomyosis has been reported in approximately 20% of women undergoing surgery for endometriosis and is most commonly seen in women with deeply infiltrative endometriosis.²⁶ While the mechanism of dysmenorrhea and chronic pain among women with adenomyosis is not entirely understood, theories include bleeding and swelling of endometrial islands confined by myometrium²⁷ and increased proliferation of nerve fibers in the endometrium.²⁸

Leiomyomas

Uterine leiomyomas usually cause abnormal uterine bleeding or mass-related symptoms. Degeneration, torsion of pedunculated subserosal fibroids, or expulsion of pedunculated intracavitary myomas through the cervix may lead to acute pain. The frequency of chronic pelvic pain in a population-based international survey of women was reported to be nearly 15% in women with fibroids compared with 3% for women without fibroids.²⁹

Pelvic inflammatory disease 

PID refers to acute and subclinical infection of the upper genital tract in women. The self-reported lifetime prevalence rates of PID range from approximately 3 to 10% in the United States.³⁰ Women with PID can develop CPP as a long-term sequelae of infection or as a result of chronic subclinical infection. As many as 30% of women with PID subsequently develop CPP,³¹ but the underlying reason that PID often leads to CPP has not been clearly established.

History and examination

The evaluation of women with CPP starts by taking a complete history that includes urinary, gastrointestinal, gynecologic, musculoskeletal, sexual, and psychosocial symptoms. This may identify all factors that could contribute to CPP (Table 1). The patient is also asked to identify all locations where she experiences chronic or persistent pain on anatomic diagrams.

Pain characteristics

Quality

The patients are asked for words that describe their sensation of pain. For example, neuropathic pain tends to be described as burning, muscular pain as aching, and uterine pain as crampy in nature. However, it is important to note that these categories have considerable overlap with other etiologies. Moreover, if patients use highly charged emotive descriptors to describe their pain (e.g., affective-type elements such as punishing/cruel), this can be a clue that centralization of pain with cortical changes is an important contributor.

Radiation

The woman is asked to identify all the primary locations where she experiences pain on a pain map (Figure 4), and also to identify all the location(s) to which the pain/symptoms travel. The pattern of pain radiation can also indicate the cause. Pain that starts in the back and/or radiates to the upper thighs may be suggestive of pelvic girdle dysfunction. Chronic nephrolithiasis will have classic renal colic with radiation of the pain to the flanks. Chronic upper abdominal pain with radiation to the shoulders and back may be suggestive of chronic pancreatitis. Diagnostic nerve blocks can potentially help in identifying a purely peripheral process; if selective anesthesia of a nerve root or discrete peripheral nerve entirely ablates the radiating pain, then a peripheral neuropathy is likely.³²

Pattern

An important question in reproductive-age women, is whether pain occurs only during menses. It may be primary dysmenorrhea or secondary dysmenorrhea. Primary dysmenorrhea is painful menstrual periods without an underlying anatomic cause, whereas secondary dysmenorrhea is due to anatomic pathology. Endometriosis is one of the common causes of secondary dysmenorrhea, but these symptoms may also be related to uterine fibroids or adenomyosis. Pain-related insomnia is an important incidental finding because it strongly indicates the need to consider central neurologic therapies as well as specific efforts to improve sleep quality.³³

Aggravating and relieving factors

Understanding the factors that provoke or alleviate the pain helps contribute to a differential diagnosis. For example, as follows:

• Pain that worsens with eating and/or improves with bowel movement is suggestive of a gastrointestinal process.
• Pain with urination or defecation can result from deep infiltrating endometriosis as well as functional and pathological disorders of the bladder or intestine.
• Pain that is altered (increased or decreased) with specific activities or position changes suggests a musculoskeletal or vascular etiology.
• Irritable bowel pain and painful bladder syndrome are typically associated with some degree of impaired visceral function.

Associated findings

Magnitude of organ system involvement can be assessed by asking the patient about the associated findings.

Sexual symptoms

The woman is asked whether she has pain with sex, and if so the location and timing of the pain. Vulvodynia or pelvic floor pain is isolated to the vaginal opening or vulva, and begins and is worsened with touch. In contrast, deep pain, particularly with thrusting, is more suggestive of endometriosis or other deep pelvic pathology.

Urinary symptoms

Women with interstitial cystitis/bladder pain syndrome often note pain with urination or a full bladder, urinary urgency, and/or urinary frequency.

Bowel symptoms

Both deep infiltrating endometriosis and acute colitis can present with associated symptoms, such as diarrhea, constipation, blood or mucus in the stool, and/or abdominal bloating, although these non-specific findings can also be seen in women with functional gastrointestinal disorders, such as irritable bowel syndrome.³⁴

Myofascial symptoms

The woman is asked if there is weakness or loss of sensation in the pelvis, buttocks, perineum, or lower extremities. Presence of a specific truncal movement that triggers the pain or if the patient can reproduce the action in the clinic can help identify the specific loci of pelvic girdle pain.

Autonomic symptoms

Autonomic symptoms include nausea related to pain, bloating, and fatigue. These symptoms reflect the general activation of the autonomic nervous system with loss of normal homeostatic function. It can be reassuring for some patients to understand that these symptoms appear to be centrally mediated responses to pain, rather than separate disorders.³⁵

Patient pain pattern phenotype has been broadly classified into two types.

• Tier 1 – Those with pelvic pain only (i.e., with a focal, unrecognized peripheral pain generator).
• Tier 2 – Those with pelvic pain and beyond (i.e., with more central sensitization of their pain). They exhibit longstanding pain and may have significant comorbid psychological dysfunction (depression, anxiety, history of posttraumatic stress disorder). Visceral pain disorders can be increased or decreased by the emotional state of the patient.³⁶ They are counseled that they will likely need a multi-modal and longer duration of treatment for their pain.

Assessment of CPP with objective tools, pain scales and questionnaires

• Pain scales and questionnaires: Pain scales and questionnaires are useful and reliable tools to assess pain intensity and also allow the distinction between nociceptive and neuropathic pain in patients presenting with more complex painful syndromes. Several factors like clinical settings, patient's gender, age, and education; and physician's personal experience guide the choice of these pain scales and questionnaires. A few of them are as follows:
  • Monodimensional pain scales: These are a simple yet useful tool for a “raw” first assessment of pain. Although they are quickly administrable in inpatient and/or outpatient service, they merely consist of a value of patient's experienced pain and are not suitable to reveal the quality of the painful experience . The most widely used monodimensional pain scales are the visual analogical scale (VAS), the numerical rating scale (NRS) and the verbal numerical rating scale (VNRS). Since they consist of numerical values, monodimensional pain scales are still often used as an outcome measure for clinical trials,³⁷ both for measuring treatment effectiveness³⁸ and for validating new developed diagnostic tools.³⁹
  • Multidimensional pain scales: This involves more complex pain evaluation where the nature and location of pain are assessed, along with the estimation of the impact of pain on daily life activities and mood. McGill pain questionnaire (MPQ), a short form of McGill pain questionnaire (SF-MPQ) and the brief pain inventory (BPI)⁴⁰ are a few examples.
  • Neuropathic pain assessment questionnaires: The neuropathic pain scale⁴¹ examines dysesthetic features of pain; PainDETECT⁴² is a self-reporting questionnaire with a schematic drawing of pain distribution and estimates pain fluctuations with time. The Leeds assessment of neuropathic symptoms and signs (LANSS Pain Scale)⁴³ is a six-item questionnaire. Neuropathic pain symptoms inventory (NPSI)⁴⁴ is a questionnaire composed of 12 items (for spontaneous ongoing pain, paroxysmal pain, evoked pain, and paresthesia/dysesthesia).
  • CPP/CPPS-specific questionnaires: Pelvic pain and urgency/frequency questionnaire (PUF) is a self-report questionnaire designed to investigate the presence of urinary urgency/frequency, pelvic pain, or sexual dysfunction. It examines symptom score as well as bother score. The pelvic pain assessment form is a gender-specific scale designed for women and developed by the International Pelvic Pain Society.⁴⁵ It is composed of two parts: the first part is filled by the patient and the last by the physician. This form gives complete information about the patient’s pain (causes, duration of pain, visual analog scale score, pain medications, and pain distribution maps), patient's past and recent history (including surgical, obstetrical, family, medical, menstrual, and gastrointestinal history; eating and health habits; genitourinary symptoms; coping mechanisms; sexual and physical abuse history).
• Objective assessment of pain: quantitative sensory testing and electrophysiology
  • Quantitative sensory testing (QST) measures the perception of mechanical, thermal, and painful stimuli delivered to determine the perceptive threshold for each sensation. QST provides integration for the regular neurological examination, giving the opportunity to better objectivate neurophysiological abnormalities in CPP/CPPS patients by establishing pain thresholds.
• Brain neuroimaging: In recent years, magnetic resonance imaging (MRI) and functional MRI (fMRI) have been suggested as tools to diagnose and objectivate chronic pain, as characteristic abnormalities have been detected in several chronic pain syndromes.^46,47,48,49 In particular, endometriosis patients were evaluated with different neuroimaging protocols. Proton spectroscopy and seed-based resting functional connectivity MRI were used to determine whether women with endometriosis display differences in insula excitatory neurotransmitter concentrations or intrinsic brain connectivity to other pain-related brain regions.⁵⁰ Vulvodynia patients have also been recently investigated with fMRI scanning (resting-state analysis).⁵¹

A complete assessment of patients’ painful experience will help in developing appropriate therapeutic protocols specially tailored for those patients, taking into account pain symptoms as well as eventual comorbidities, psychological features, and functional QoL status. Future investigations are warranted to promote diagnostic tools accuracy and to correlate instrumental findings.

Physical examination

The physical examination is an essential component in the evaluation of pelvic pain but can also be painful and emotionally stressful for the patient. To reduce stress, it is helpful to conduct the examination in a systematic, gentle, and interactive approach. The primary goal is to identify the anatomic locations and structures that reproduce the patient's pain.

The examination begins with the back while the patient is seated. The examiner should apply focal pressure to the sacrum, coccyx, sacroiliac joints, and paraspinal muscles. Tenderness in the area of palpation as well as referral or radiation to the back and/or abdominal wall suggests a musculoskeletal cause of pain. Spinal curvature, abnormal posture, or asymmetry of the pelvic girdle or gait also suggest a musculoskeletal component to pain (Figure 5).⁵² The abdominal examination is then performed with the woman supine (Figure 6). The examiner must be able to differentiate diffuse lower abdominal pain from focal pain associated with a taut band of muscle or trigger point. Worsened pain during flexion, a "positive Carnett's sign", is more likely a result of pain in the abdominal wall, whereas improved pain during flexion suggests an underlying visceral etiology (Figure 7).

Pelvic examination

The pelvic examination is typically performed in the lithotomy position (Figure 8).

Local examination

Inspection

To look for vulvar scars, lesions, skin changes, swelling, cysts, or asymmetries in the vulvar architecture and gently palpate scars to assess for tenderness.

Cotton swab test

The cotton swab test is suggested specifically for women with vulvar pain or dyspareunia. The moistened soft end of a cotton swab is used to press lightly, beginning at the lateral thighs and moving medially to include evaluation at the 1-, 4-, 6-, 8-, and 11-o'clock locations of the vestibule (Figure 9).

Examination of pelvic floor

The pelvic floor, anterior vaginal wall, cervix, uterus, and vaginal fornix are palpated with a well-lubricated single finger to assess for contracted or painful muscles and trigger points. Then the levator ani (3- to 5-o'clock and 7- to 9-o'clock positions), internal transverse perineal, and obturator internus (2 to 3 o'clock and 9 to 10 o'clock) muscles are systematically palpated. The bladder, urethra, and rectum are then palpated followed by the cervix, posterior lower uterine segment, adnexa, and lateral vaginal fornices. Some experts have suggested using a four-point scale to rate relative tenderness, which has good inter-rater reliability, but the modest reliability of this pelvic floor muscle hyperalgesia scale (ICC between 0.4 and 0.8) suggests that repeat evaluation during a follow-up visit may be helpful to improve precision.⁵³

Bimanual examination

Helps in distinguishing among pain arising from the pelvic floor, bladder, uterus, and adnexa (vaginal fingers) versus the abdominal wall (Figure 10).

Rectovaginal examination

Rectovaginal examination should be considered selectively for deep pelvic pain presentations, to identify nodularity or tenderness in the rectovaginal septum or uterosacral ligaments, which may occur with deep infiltrating endometriosis.

Per speculum examination

Use the smallest speculum that allows adequate visualization of the cervix, posterior fornix, and vaginal walls. Cervical, and possibly vaginal cultures, are obtained if there is a concern for cervicitis, vaginitis, or PID (i.e., abnormal vaginal or cervical discharge). Careful inspection of the posterior fornix is particularly important if the patient has symptoms of endometriosis, as transmural deep infiltrative endometriosis lesions can occasionally be seen in this area (Figure 11).

Investigations

Laboratory or imaging studies for women with CPP are guided by the information gained during the above history and physical examination.

Laboratory tests

These are done to exclude other causes for the patient's symptoms. For example, women with pelvic pain often have a pregnancy test (if applicable), urinalysis, and tests for gonorrhea, chlamydia, and trichomonas. Women with a urinalysis suggestive of infection then undergo urine culture. Women with a recent travel history and gastrointestinal symptoms undergo testing for intestinal infection.

Ultrasound

A pelvic ultrasound is typically performed for females with acute or chronic pelvic pain who also have an enlarged uterus, an adnexal mass, other structural abnormality on physical examination, or symptoms of heavy or irregular bleeding.⁵⁴ Deep infiltrating endometriosis (DIE) can be identified by routine transvaginal ultrasound. This "negative sliding sign" when assessed with dynamic ultrasound, has a sensitivity of 85% and specificity of 96% for the presence of DIE.⁵⁵

Magnetic resonance imaging

In a Cochrane review of six studies with 266 participants, MRI had excellent sensitivity (94%, 95% CI 90–97%) and specificity (77%, 95% CI 44–100%) for the diagnosis DIE, thus approaching the criteria for a replacement diagnostic test in lieu of surgical biopsy.⁵⁶

Computed tomography (CT)

Computed tomography (CT) scans are infrequently utilized unless there is evidence of acute enteritis or colitis. Provocative tests have a role in research protocols to characterize visceral hypersensitivity as a risk factor for developing chronic pain, but the available data do not support their use in the clinical setting.^57,58

Role of laparoscopy

Laparoscopy can be used for both diagnosis and treatment in women with some causes of CPP (e.g., endometriosis, adhesions) but is also associated with surgical risks (e.g., bleeding, infection, visceral organ injury). It is mostly offered to women who decline or do not benefit from medical, physical, and/or cognitive behavioral therapy. However, the exact timing of when to offer laparoscopy is a collaborative decision with the patient and there are no consistently accepted guidelines.

Some women will complete the evaluation above and still not have clear signs, symptoms, or test results that help identify the cause of their pelvic pain. Women with a negative laparoscopy are diagnosed with idiopathic CPP that is generally managed like other centralized chronic pain syndromes. Over time, many of these patients will eventually develop more explicit symptoms that place them in discrete categories like irritable bowel syndrome, painful bladder syndrome, myofascial pelvic pain syndrome, or vulvodynia.

Treatment

After completing evaluation, identified potential causes of CPP are treated with therapy targeted to the specific problem. However, some women will have no identified cause of pain and others will have persistent pain despite treatment of presumed etiologies. Many women will carry a clearly defined diagnosis such as irritable bowel syndrome, interstitial cystitis/bladder pain syndrome, or surgically documented endometriosis, but have pelvic pain that is not related to their bowel, bladder, or uterine function. Regardless of whether they have met minimum diagnostic criteria for known overlapping pelvic pain conditions, patients who describe persistent CPP that does not respond to syndrome-specific management may benefit from multimodal treatments of CPP of undefined cause. A major goal of treatment is to improve function.

Women with CPP associated with a probable etiology

• Hormonal therapy to women who have a cyclic component to their pain.
• Procedural treatments such as a peripheral nerve block or consider surgical release to women with suspected focal nerve pain from nerve impingement or entrapment.
• Combination of pharmacologic treatment, non-pharmacologic therapy, and procedures to women with myofascial or musculoskeletal pain. The treatment is aimed to address the most severe or bothersome symptoms.

When the patient's history and physical examination suggest endometriosis that is either undertreated or has likely recurred (especially deep infiltrating disease), we consider laparoscopic excisional therapy.

Women whose pain resolves after targeted therapy require no further treatment. Women whose pain persists despite focused treatment are then treated as below.

For women with no identified cause or women whose symptoms do not resolve with targeted treatment

• We should ensure a thorough differential diagnosis, based on a detailed history and physical examination, prior to treatment so that all potential relevant causes of a woman's pain have been explored.
• Treat pain with a goal of regaining function. We often will use both pharmacologic and non-pharmacologic therapies simultaneously.
• Develop a positive outlook about each patient's prognosis.

Importance of identifying, classifying, and treating neuropathic pain

Acute neuropathic pain

Acute neuropathic pain should be suspected when a patient has pain in the distribution of a sensory nerve following a surgery or acute injury. The aim is to reduce the pain symptoms while resolving the underlying nerve insult, if possible. One goal of treatment is to prevent the development of cortical changes that perpetuate pain expression and become chronic neuropathic pain.

• For women who have undergone an index surgical procedure and have severe symptoms strongly suggestive of a specific peripheral nerve injury or irritation rapid return to remedy a nerve injury is attempted.
• For women with mild symptoms following a procedure, or symptoms without an antecedent procedure, central agents along with anesthetic injections or topical anesthetics, such as a lidocaine patch are prescribed.

Chronic neuropathic pain

Chronic neuropathic pain is more chronic in nature, such as 3 to 6 months' duration or longer, treatment begins with a combination of non-pharmacologic therapy, a neuromodulator, and possibly a nerve block.

Baseline non-surgical interventions

Initial pharmacologic treatment

The World Health Organization (WHO) analgesic ladder, which was developed to guide treatment of cancer pain in adults, suggests initial treatment of chronic pain with non-opioid medications.⁵⁹ These medications are generally well tolerated, have few side-effects and reasonable safety profiles, and are low cost.

• Nonsteroidal anti-inflammatory drugs (NSAIDs) – NSAIDs are often used in the treatment of chronic pain.
• Topical analgesics.
• Muscle relaxants – cyclobenzaprine, methocarbamol, metaxalone, carisoprodol, tizanidine.
• Specific role of empiric hormonal therapy.

Subsequent targeted interventions

Targeted therapies

Nonsurgical

Physical therapy – This typically targets dysfunction of the pelvic floor, hip, back, and abdominal wall muscles. Therapeutic interventions often include manual therapy, tissue mobilization, and biofeedback but can also include other techniques such as acupressure and ultrasound therapy (Figure 12).⁶⁰

Trigger point injection – Trigger points are focal, hypersensitive nodules within muscles that are markedly painful to firm palpation and may be focal pain generators. Trigger points are frequently identified in abdominal wall or pelvic floor muscles in patients with CPP and are often associated with referred pain, motor dysfunction, and occasionally, autonomic symptoms. A common treatment for trigger points is injection with local anesthetics. Successful treatment is considered to be improvement in pain that substantially outlasts the anesthetic's duration of action. A common treatment for trigger points is injection with local anesthetics (Figure 13).

Nerve block – peripheral nerve blocks (PNB) are widely used for surgical anesthesia as well as for both postoperative and non-surgical analgesia. PNBs can also be used for diagnosis and treatment of nerve pain (Figure 14).

Surgical

Surgical options should be considered when clinical suspicion for conditions that may be responsive to surgery is high. Examples of such causes may include severe deep infiltrating endometriosis, a reversible process iatrogenically caused by a prior procedure (such as pain following hysteroscopic permanent contraception [e.g., Essure], IUD placement, endometrial ablation, vaginal mesh procedures for urogenital prolapse, or loop electrosurgical excisional therapy), focal pain that is reproduced with palpation of a leiomyoma, chronic adnexal pathology.

When to reverse the prior procedure – one clinical challenge in treating women with CPP is deciding when to reverse a prior procedure that either implanted a foreign body or that could have caused nerve entrapment, either with suture or scarring. In our practice, we consider procedure reversals for women whose pain is reproducible on examination and correlates with the prior procedure and who have not responded to medical and non-pharmacologic therapy.

Additional surgical procedures aimed to reduce pain – women with CPP that is refractory to the above non-pharmacologic and medical therapies often ask about surgical options to reduce their pain.

• Presacral neurectomy – resection of the sympathetic nerves of Cotte triangle (over the sacral promontory) has been thought to block transmission of visceral afferent signals from the pelvic organs and thereby reduce pain.
• Lysis of adhesions – routine lysis of adhesions does not appear to be helpful in treating CPP and therefore is not advised.⁶⁰ Although adhesions are commonly part of the differential diagnosis of CPP, the exact structural relationships (e.g., connecting pelvic organs, entrapping specific nerve bundles) or mechanisms (e.g., organ tethering) that would cause adhesions to contribute to cyclic or continuous pain are not well established.
• Hysterectomy – we have proposed the phrase "chronic uterine pain" to describe women with the repeated finding of uterine tenderness on examination that does not respond to medical therapy and is not caused by endometriosis.⁶¹ In some cases, symptomatic leiomyoma or adenomyosis, even when not markedly distorting the uterus, may be ultimately contributing to symptoms as well. In these women, where the diagnosis is not clearly defined by palpable pathology, they are viewed as having a functional condition analogous to painful bladder syndrome or irritable bowel syndrome. For women who have completed childbearing, hysterectomy can be a reasonable treatment option.

Less studied targeted treatments

• Vaginal anxiolytics: vaginal benzodiazepines as a temporary adjunct to facilitate pelvic floor physical therapy.
• Botulinum toxins A and B: Botulinum toxin A (BTXA) injections may be helpful for some women with CPP caused by refractory myofascial pelvic pain syndrome.^{62,63,64,65,66,67} While BTXA may reduce general pelvic pain as well as myofascial pain, BTXA injection is typically performed in women with pelvic floor spasm that is refractory to PT.

Interventions for central sensitization or neuropathic pain

For CPP that is unresponsive to targeted therapy or that is non-specific, the field of pain medicine accepts a hypothetical significant role for altered central pain processing and widely employs medications that alter circulating neurotransmitters thought to underlie that imbalance (i.e., neuromodulators).

Neuromodulators

General approach

In practice, treatments for CPP include anticonvulsants, tricyclic antidepressants (TCAs), and serotonin norepinephrine reuptake inhibitors (SNRIs) because of their demonstrated efficacy in treating other neuropathic pain syndromes, tolerability, and relatively safe side-effect profile.⁶⁰ If the patient does not achieve pain reduction at a therapeutic dose, then it is advised to move on to the next class of drugs. Muscle relaxants can be used in combination with these medications for breakthrough pain. Plans for pregnancy are an important consideration; these agents should be used with caution for patients desiring to conceive.

Approach to anticonvulsant dosing

• Gabapentin – if the patient is of normal body weight and does not report substantial issues with fatigue, a starting dose of 300 mg once a day is generally prescribed and titrated up by 300 mg/day every 5 to 7 days (in divided doses three times a day) until pain improves sufficiently, side-effects preclude further dose escalation, or the patient reaches a maximum dose of 3600 mg/day.⁶⁸
• Pregabalin – when prescribing pregabalin, it is advisable to begin with oral capsules of 50 to 75 mg given two to three times a day.
• Tricyclic antidepressants – TCAs are often considered first-line treatment of centralized pain conditions.
• Mechanism of action – TCAs inhibit reuptake of serotonin and norepinephrine, thereby increasing the amount of available norepinephrine and serotonin.⁶⁹ The target is thought to include dysfunction of the descending pain modulatory system; increased availability of norepinephrine and serotonin in the descending pain modulatory pathways appears to decrease pain sensitivity.
• Dosage – oral amitriptyline is prescribed at a dosage of 10 to 25 mg at night, if the patient is of normal weight and does not report substantial issues with fatigue. Amitriptyline may not be well tolerated due to the anticholinergic side-effects of fatigue, dizziness, dry mouth, and constipation.
• Serotonin norepinephrine reuptake inhibitors – SNRIs, such as duloxetine, venlafaxine, and milnacipran, appear to increase centrally available serotonin and norepinephrine. Duloxetine for CPP patients is started at 30 mg daily (as in fibromyalgia or chronic musculoskeletal pain) and then increased to 60 mg daily after 1 week.

Other antiepileptics – antiepileptic sodium channel blocking agents, such as phenytoin, carbamazepine, oxcarbazepine, lamotrigine, tiagabine, and topiramate, cause a general decrease in all neuron membrane excitability and reduction in the spontaneous firing of sensory neurons.⁷⁰

Nonpharmacologic therapies

Nonpharmacologic strategies, including exercise, peripheral neuromodulation, and cognitive behavioral therapy, can be used in conjunction with pharmacologic or surgical therapy.

• Cognitive behavioral therapy and mindfulness – cognitive behavioral therapy (CBT) is a problem-focused, goal-directed psychological therapy in which patients are taught to recognize the contributions of their thoughts and behaviors to their pain experience, so that they can then modify these thoughts and behaviors in a more adaptive way.⁷¹ CBT can be highly effective therapy for multiple chronic pain conditions,^72,73,74,75 and research regarding CBT for the treatment of CPP suggests a positive impact, although the body of evidence is limited.⁷⁶
• Exercise – exercise interventions appear to be helpful for a variety of chronic pain conditions,⁷⁷ including CPP,^78,79,80 and dysmenorrhea.^81,82,83,84 Improvements have been reported in pain, quality of life, physical function, mood, sleep, and self efficacy. Physical activities that are beneficial are varied, and may include walking, aerobic, strength training, yoga, pilates, and swimming.

Nonpharmacologic therapies of less clear benefit

• Acupuncture – acupuncture includes needling, auricular point manipulation, and moxibustion (warm acupuncture).⁸⁵ For women who desire a trial of acupuncture for CPP, there appears to be little risk and it may be helpful.
• Neuromodulation – peripheral neuromodulation (including transcutaneous electrical nerve stimulation [TENS], percutaneous tibial nerve stimulation [PTNS], sacral neuromodulation [SNM], and pudendal neuromodulation) involves delivering electrical stimulation to a sensory nerve, which is thought to reduce nociceptive processing of pain signals.⁸⁶
• Dietary strategies – dietary intervention to treat CPP is an area of developing interest based on some studies supporting avoidance-diets in treating bladder pain syndrome, functional bowel syndromes, and celiac disease.

Adjuvant therapies – these approaches are not used widely but have been reported. Further evaluation of these treatments in women with CPP is advised before routine use and their use for CPP in women are limited and contradictory.^87,88,89

• Antipsychotic medication.
• Cannabinoids.

Therapies to consider cautiously

• Opioids – for postoperative pain or brief pain flares, the short-acting opioids hydrocodone or oxycodone (with or without acetaminophen) in 5 mg oral doses are typically prescribed every 6 hours as needed.
• Tramadol – an additional treatment option is tramadol (50 mg orally every 6 hours), which is both a combined μ-opioid agonist and norepinephrine and serotonin reuptake inhibitor.⁹⁰

In conclusion, pelvic pain is an important cause of impaired quality of life of females in the reproductive age group. Evaluation and treatment involves a systematic approach with an aim to improve the well-being of the patient.

PRACTICE RECOMMENDATIONS

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