In order to evaluate and treat a woman with pain of urogenital origin, one must have a good understanding of chronic pelvic pain (CPP) in general. This encompasses a broad differential diagnosis spanning multiple organ systems. This chapter will present an overview of CPP, highlighting some of the more common etiologies, and providing a more expanded discussion of two disorders very commonly encountered by specialists in female pelvic medicine and reconstructive surgery, namely, interstitial cystitis/painful bladder syndrome (IC/PBS) and vulvodynia.

Chronic Pelvic Pain

CPP traditionally has been defined as cyclic or noncyclic pain in the lower abdomen or pelvis, continuous or intermittent, of at least six months duration that limits daily activities or function.^1,2 However, no universally agreed upon definition exists. The term CPP implies that pain is in the “pelvis,” but its location can occur anywhere in the anatomic pelvis, including the abdominal wall from the navel caudad, as well as the low back or buttocks.¹ This wide breadth of location and consequently multiple possible sources of pain—both somatic and visceral—make the condition of CPP difficult to manage and study.

It is estimated that one in five women aged 18 to 50 report pelvic pain for 12 months or more.¹ Worldwide the prevalence of CPP is estimated at 2% to 24% of women.³ An analysis of a large primary care database in the United Kingdom found 38 per 1,000 women per year presented with CPP, which was similar to the rate of visits for asthma, 37 per 1,000.⁴ Of diagnoses made in these women, 20.2% were gynecologic, 30.8% urinary, and 37.7% gastrointestinal.⁴ Costs to the patient are great and include frustration and suffering often leading to inability to work and perform daily activities, strain on relationships, and negative impact on overall health and quality of life.

Endometriosis

Endometriosis is a common cause of CPP. Up to 87% of women with CPP are diagnosed with endometriosis. It is defined by the presence of endometrial glands and stroma outside the uterine cavity. Early menarche and prolonged menstrual cycles are risk factors for endometriosis, and women with a first-degree relative with endometriosis have seven to ten times the risk of developing endometriosis. Higher parity and longer lactation are associated with a lower risk. Endometriosis is estimated to affect 6% to 10% of reproductive age women.⁵

Interstitial Cystitis/Painful Bladder Syndrome

IC is one possible etiology of CPP. Once again, there is a lack of consensus regarding the definition and even the terminology to describe this syndrome. In general, it is a disorder characterized by urinary frequency, urgency or persistent urge to void, and pain perceived to be associated with the bladder or urethra. In 1987, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) put forth criteria to define IC (Table 16-1). Despite their intended use for research purposes, these criteria were widely applied to clinically diagnose this condition. The clinical utility of these criteria has been challenged. Many women who are diagnosed clinically with IC fail to meet the NIDDK criteria; it is generally well accepted that these criteria are too restrictive for clinical use.^7-9 There has been discussion about changing the terminology from IC to PBS or bladder pain syndrome (BPS) or some combination of these. The NIDDK now advocates using the term IC/PBS to include any case of urinary pain not attributable to other causes. The International Continence Society defines PBS as “a complaint of suprapubic pain with bladder filling, accompanied by other symptoms such as increased daytime and night-time frequency, in the absence of obvious infection and or other obvious pathology.” The European Society for the Study of IC/PBS advocates using the terminology “bladder pain syndrome” rather than IC to describe pelvic pain, pressure, or discomfort perceived to be related to the bladder, lasting for six months or more and accompanied by at least one other urinary symptom such as persistent urge to void and frequency. PBS is a diagnosis of exclusion; other possible etiologies must be excluded. The American Urological Association and the Society for Urodynamics and Female Urology define interstitial cystitis/bladder pain syndrome (IC/BPS) as “an unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms of more than six weeks duration, in the absence of infection or other identifiable causes.”⁹ In the 2011 AUA Guidelines, they reported that their systematic review found insufficient evidence to create guidelines for diagnosis of IC/PBS, and therefore the guidelines generated are based on clinical principles and expert opinions. Despite lack of evidence to support diagnosis, the reviewers did determine that enough data exist to support management of the syndrome used in conjunction with clinical principles and expert opinions.⁹

Given the lack of consensus about the definition of IC/PBS and how it is diagnosed, it has been difficult to study its epidemiology. Prevalence estimates are wide ranging from 4.5 to 197/100,000 in studies looking at physician-assigned diagnosis and 67 to 865/100,000 women in studies using patient self-report.^10-13 More recent published data from two questionnaire/survey-based studies, the Nurses Health Study and the RAND Interstitial Cystitis Epidemiology study, revealed a prevalence of 2.3% to 6.5%.^14,15 IC/PBS is more common in women and Caucasians. It is diagnosed most commonly in the fifth decade of life but can be diagnosed at any age.¹⁶ The Nurses Health Study included women aged 58 to 83 and found increasing prevalence with age: 1.7% in women less than 65 and 4% in women older than 80.¹⁴

Vulvodynia

The International Society for the Study of Vulvovaginal Disease (ISSVD) defines vulvodynia as “vulvar discomfort, most often described as burning pain, without relevant visible findings or a specific, clinically identifiable neurologic disorder.”¹⁷ This is another pain syndrome that is a diagnosis of exclusion, and distinct infectious, neurologic, and dermatologic disorders must be ruled out. The ISSVD also defines subsets of vulvodynia as generalized or localized. Within these subsets, pain is described as provoked, unprovoked, or mixed. Generalized vulvodynia would involve the entire vulva, whereas localized may involve only the clitoris or vestibule (clitorodynia and vestivulodynia, respectively). Provoked vulvodynia would include cases where pain occurs with physical contact, whereas in unprovoked, discomfort occurs without a trigger.

Chronic Pelvic Pain

CPP can be of visceral or somatic origin or both. Visceral pain may originate from the gastrointestinal, reproductive, or urinary system, and somatic pain may arise from the bony pelvis, muscles, and connective tissues. Pain can be of central (arising from the level of the CNS) or peripheral (arising from the end organ) origin. Many structures in the pelvis have a common embryologic origin. The urogenital ridge arises from the intermediate mesoderm in the embryo and gives rise to the urinary and genital systems.

Given the vast differential diagnosis for CPP, there is no one pathophysiology. For many of these conditions, it is poorly understood how they cause pain, and it is not well elucidated how the pain of these conditions becomes chronic even when identifiable lesions are treated or the origin of the pain is removed. This is true in patients with endometriosis and has been reported in patients with IC who undergo cystectomy. For many of these pain disorders there is believed to be an element of neural upregulation that may be both chemical and structural that increases both efferent and afferent activity. This results not only in abnormal sensation but also in function. There is considerable clinical and molecular evidence that pain in one pelvic organ can affect other pelvic organs. The mechanism of this viscero-visceral interaction, or cross-sensitization, is not completely understood. Several proposed mechanisms attempt to explain this phenomenon. Neurologically this is thought to happen at one or a combination of levels. Pelvic viscera have afferents projecting to dorsal root ganglia via hypogastric, pelvic splanchnic, and pudendal nerves. At this level, it is hypothesized that stimuli from a diseased organ will cause release of neurotransmitters via axonal connections with other neighboring organs. This leads to neurogenic inflammation in an organ adjacent to the diseased organ. Viscero-visceral interaction may also occur at the spinal level. Sensory input from more than one organ can converge on one spinal interneuron, and input from one organ enhances the input from other organs. Convergence at the spinal cord of afferents from the uterus, bladder, and colon has been demonstrated in animal models. The third neurologic level thought to contribute to this phenomenon is supraspinal where there is a process of amplification of visceral afferent input in the brainstem nuclei.¹⁸

Women with one pain diagnosis will suffer more severe pain from pathology affecting another organ system. This process of two organs enhancing pain in each other, also known as viscero-visceral hyperalgesia, is seen clinically. It has been demonstrated that subjects with irritable bowel syndrome (IBS) and dysmenorrhea have more pelvic muscle, intestinal, and menstrual pain than those with IBS or dysmenorrhea alone. Treatment of IBS with dietary modification improved dysmenorrhea, and hormonal treatment of dysmenorrhea improved IBS symptoms. Women with urinary calculi and dysmenorrhea experienced more referred abdominal and low back pain as well as more urinary and menstrual pain than those with either condition alone. Lithotripsy of the urinary stone improved menstrual symptoms, and hormonal treatment of dysmenorrhea reduced urinary symptoms.¹⁹

Because of common embryologic origins, cross-sensitization, and the phenomenon of afferent activity ultimately impacting function, many women with CPP have more than one associated diagnosis. Among women with CPP, 76% also had endometriosis, 82% IC, and 66% had both.²⁰ Patients with CPP involving more than one organ system also have more severe and consistent pain. The presence of gastrointestinal and urologic symptoms is associated with more severe dysmenorrhea and dyspareunia.¹

CPP occurs most commonly in women of reproductive age but can occur at any age, with the most common causes of CPP being endometriosis, IBS, and IC. Additionally, the psychological aspect of CPP cannot be discounted. Pain is a phenomenon that is ultimately perceived at a cognitive level, and therefore the patient’s perception of the pain and her response to that pain is very much a part of her experience. The purpose of understanding the psychological dimensions of the patient’s pain is, therefore, not to discount the pain as a purely psychological phenomenon, but to appropriately treat this aspect of the pain experience as well. Women who have CPP score poorly on general physical health questionnaires.² There is some evidence that women with vulvodynia score worse on relationship, emotion, and physical activity domains of testing than women with other vulvovaginal disorders.²¹

Many studies have looked at a history of abuse in women with CPP and have found that it is common, occurring in 40% to 50% of women with CPP. It is unclear if the abuse itself leads to a painful condition either directly or indirectly through a process of hypersensitization of the patient, or if the psychological trauma of the abuse predisposes her to experience pain.¹ A study of women newly diagnosed with IC with and without a history of abuse showed more tenderness of the suprapubic region, vulva, levator muscles, posterior vaginal wall, cervix, and rectum in women with a history of abuse. Women with a history of abuse also had worse female sexual function index scores as well as more urinary frequency and nocturia.²² Psychological comorbidities were found in one study to predispose to noncyclic pelvic pain.²³

The diagnosis of CPP can be made for a broad range of patients with a variety of symptoms. Several organ systems inhabit the pelvis—urogenital, gastrointestinal, and musculoskeletal. Within each of these, there are multiple disorders that can cause pain, and symptoms from many of these disorders can overlap. In addition, for patients with chronic pain, the pain itself can become a disease process. Table 16-2 provides a list of possible causes of CPP. As stated above, there are far too many potential etiologies to address them all. For the purposes of this chapter, we will focus on a few and discuss chronic pain as its own entity.

Endometriosis

The pathophysiology of endometriosis and specifically of how it causes chronic pain is not completely understood. Endometrial tissue is thought to spread into the pelvis via retrograde menstruation, although hematogenous or lymphatic spread and coelomic metaplasia are also proposed mechanisms. It is thought that the endometrial implants lead to chronic inflammation that ultimately leads to pain. In some instances, implants may actually invade nerve fibers and cause pain.

Interstitial Cystitis/Painful Bladder Syndrome

The pathophysiology of IC/PBS is also not well understood. It is thought to originate from a dysfunction of the glycosaminoglycans (GAGs) in the bladder epithelium. These hydrophilic GAGs bind water to transitional cells and block urinary solutes from reaching the bladder interstitium. If the GAG layer is disrupted or dysfunctional, solutes can permeate the epithelium. This leads to the degranulation of mast cells that release histamines, cytokines, vasoactive, and nociceptive mediators. Bladder afferents become sensitized. Input from these afferents to the dorsal horn is increased. This leads to hyperexcitability at the CNS level (Figure 16-1).^25,26

Vulvodynia

The underlying etiology of vulvodynia is unknown. Like many causes of chronic pain, it is multifaceted and affected by the interplay of physical, psychosocial, and sexual factors. Several studies have looked at the relationship of urogenital infections and vulvodynia, and women who have had multiple infections may be at increased risk for the development of vulvodynia. A history of frequent yeast infections is commonly reported among women with vulvodynia, but it is unclear if this is somehow causal, sensitizing, or coincidental.²⁷ There may be a genetic predisposition to a prolonged, abnormal inflammatory response in women with vulvodynia.^28,29

Allodynia and hyperalgesia in the absence of physical findings are common in neuropathic pain disorders, and are frequently reported in vulvodynia. Some studies found differences in nerve ending density and nocioceptor sensitivity in patients with vulvodynia. Neovascularization and increased blood flow may also play a role. Pelvic floor muscle abnormalities such as difficulty contracting and relaxing the muscles very commonly coexist with vulvodynia, and may be a result of the chronic pain or may be causative or contributory.

OCPs may alter vulvar epithelium because of loss of cyclic changes, but data are not conclusive about the effect of OCP on vulvar epithelium and pain thresholds. Estrogen’s effect on the vulva is complex and incompletely understood. A lack of estrogen may be associated with more nerve fibers in the vulva. However, estrogen can also promote changes that lead to a lower pain threshold.^30-33

History

A thorough obstetric, gynecologic, medical, and surgical history is key. Incorporating a depression screening tool into the evaluation of these patients may be useful. A detailed social history including screening for past or current abuse is a difficult but important part of the history. Exploring issues a patient may have at home and what their supports are will provide useful information. The patient history should be taken in privacy with the patient alone. Patients with extensive history of psychiatric disease, positive depression screening, history of abuse, and those who voice difficulty coping with pain should be referred for complete psychiatric evaluation and social services.

Every effort should be made to determine an underlying etiology or etiologies for the pain. However, it is likely that one will not be found and treatment will have to be aimed at symptom relief. Patients may need to be scheduled for a separate visit specifically aimed at exploring their pelvic pain. Allowing the patient to share her story will provide information and help establish a trusting relationship with the provider.²

When eliciting the history of present illness, discussing all elements of the pain is essential (Table 16-3). The nature of the pain, severity, timing, location, and associated symptoms must be investigated. Symptoms are often nonspecific. However, some may point to a diagnosis. One study found that women with endometriosis more commonly report “throbbing, gnawing and dragging pain to the legs.” Those found at laparoscopy to have deep disease more commonly reported “shooting rectal pain” and “a sense of their insides being pulled down.”³⁴

Understanding any associated urinary, gastrointestinal, and sexual symptoms is important. Dyspareunia as a specific form of CPP is discussed in depth elsewhere in this text. Patients with pelvic pain, even whose primary etiology does not seem to be gynecologic, can experience pain related to her menses. Another dimension of the interview is understanding the impact of the pain on the patient’s ability to function. Questionnaires are useful tools to augment the evaluation. They should not replace an in-depth history, but may help to capture and elucidate symptoms. A visual analog scale is also a useful tool to quantify and follow pain. Many advocate that patients use body maps (Figure 16-2) to illustrate pain. This will help elicit multiple areas of pain if present or if pain is in a dermatomal or myotomal distribution versus a less distinct distribution more typical of visceral pain. The short form of the McGill Questionnaire (Figure 16-3) has been used for many years in patients with CPP.^2,35 The International Pelvic Pain Society has a form that can be downloaded from their Web site that includes a patient self-assessment form as well as a history and physical examination form for physicians (http://www.pelvicpain.org/resources/handpform.aspx).

Interstitial Cystitis/Painful Bladder Syndrome

Once again, a detailed and complete history and physical is critical to the assessment of patients with the possible diagnosis of IC. Common symptoms are depicted in Figure 16-4. Other common symptoms include the sensation of “bladder spasms,” suprapubic pressure, and dyspareunia.³⁶ Patients often report that they have had multiple urinary tract infections with negative urine cultures.

The history of present illness must include the nature of the pain or discomfort, urinary symptoms, and duration and progression of symptoms. Patients with IC often describe episodes of increased pain or worsened urinary frequency commonly referred to as “flares.” It is important to elucidate any exacerbating factors or “triggers” of symptoms as well as anything they have found that alleviates symptoms. Any history of bowel or sexual symptoms should also be obtained. Getting a general idea of fluid intake and intake of common bladder irritants is useful. As is true with chronic pain patients in general, it is likely that the IC patient has seen doctors prior to seeing you, so a thorough history of any testing or treatments, as well as records of these if possible, should be sought. As always, a complete medical, surgical, and obstetric and gynecologic history will be informative, particularly in guiding evaluation for other possible diagnoses that may be causing or contributing to the symptoms. For example, patients who have had prior abdominal or pelvic surgery may warrant different testing than one who has not. Patients may also have other chronic pain disorders or autoimmune diseases that need to be considered.

There are several questionnaires specifically used to assess IC symptoms including the O’Leary–Sant Interstitial Cystitis Symptom and Problem Index, the Pelvic Pain and Urgency/Frequency symptom scale (PUF Questionnaire, Figure 16-5), and the University of Wisconsin Interstitial Cystitis Scale. The PUF Questionnaire was designed as a screening tool, and the O’Leary–Sant was designed as an outcome measure (Figure 16-6).³⁷ These questionnaires can be helpful to capture and follow symptoms but cannot be used alone for diagnosis.

Vulvodynia

The history of present illness in women complaining of vulvar pain should be as detailed as possible to help distinguish subsets discussed earlier (eg, localized, generalized, provoked, unprovoked, or mixed). Eliciting provoking factors, quality, location, and duration of pain is essential.

Physical Examination

The physical examination will also be extensive, keeping in mind all the various organ systems potentially involved. The examination must be performed gently and carefully because it is likely to be painful and stressful for the patient. She may need time to recover between portions of the examination. The goal of the examination is to determine if there is any obvious pathology but also to get a better understanding of the anatomic location of the pain. If the pain can be replicated by certain maneuvers during the examination, this may shed light on the underlying processes. Throughout the examination whenever pain or tenderness is elicited, the patient should be asked how that pain compares in quality and intensity with the pain she usually feels.

The patient’s general demeanor can be telling, regarding psychological and physical status. Assessing posture and gait may give clues to musculoskeletal issues contributing to pain. Abnormal posture over time can cause weakening of some muscles and strain of others. This can lead to imbalances, instability, and increased tone and tenderness. Exaggerated lumbar lordosis and thoracic kyphosis is often referred to as the “pelvic pain posture.”¹ It is not clear if these are adaptive because of long-standing pain or contributory to pain. Assessment of the patient’s back may also lead to clues regarding the etiology of the pain. Scoliosis, spinal tenderness, and sacral iliac joint tenderness can be sources of pain referred to the abdomen/pelvis.