Version May 2024
INTRODUCTION — Chronic pelvic pain (CPP) is generally defined as noncyclic pain perceived to be in the pelvic area that has persisted for three to six 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. After completing an evaluation, identified potential causes of CPP (eg, endometriosis or adnexal mass) 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. Notably, 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.
This topic will present the treatment of the adult woman with residual or undefined CPP. Topics on the causes and evaluation of CPP in adult women, as well as the evaluation of children and adolescents, are presented separately:
●(See "Chronic pelvic pain in nonpregnant adult females: Causes".)
●(See "Chronic pelvic pain in adult females: Evaluation".)
●(See "Chronic abdominal pain in children and adolescents: Approach to the evaluation".)
In this topic, when discussing study results, we will use the terms "woman/en" or "patient(s)" as they are used in the studies presented. However, we encourage the reader to consider the specific counseling and treatment needs of transgender and gender expansive individuals.
OUR APPROACH
Is there a probable versus unidentified cause of CPP? — The optimal approach to the management of CPP of unclear etiology is not known, in part because the field of CPP lacks well-designed, large-volume trials with appropriate longitudinal follow-up to validate existing treatments, and in part because pain is an end symptom of diverse etiologies (table 1). Therefore, the management of CPP is largely based on clinical experience and studies evaluating treatments for other types of chronic pain syndromes (eg, fibromyalgia, back pain, migraine).
●Women with CPP associated with a probable etiology – Initial treatment of pain from a likely etiology is aimed at addressing the presumed cause (table 1). It is important to note that multiple treatments can be used simultaneously to address the patient's collection of symptoms and dysfunction. There is no one single approach that treats all women with CPP. In our practice:
•We offer hormonal therapy to women who have a cyclic component to their pain. (See 'Specific role of empiric hormonal therapy' below.)
•We offer procedural treatments such as a peripheral nerve block or consider surgical release to women with suspected focal nerve pain from nerve impingement or entrapment. (See 'Importance of identifying, classifying, and treating neuropathic pain' below and 'When to reverse prior procedure' below.)
•We offer a combination of pharmacologic treatment, nonpharmacologic therapy, and procedures to women with myofascial or musculoskeletal pain. The treatment is ordered to address the most severe or bothersome symptoms first. (See 'Importance of identifying, classifying, and treating neuropathic pain' below and 'Baseline nonsurgical interventions' below and "Myofascial pelvic pain syndrome in females: Treatment".)
•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. Key signs that might point to recurrence include a new persistent pelvic mass, tender nodules in the cul de sac, or periuterine tenderness, including the vaginal fornices, especially when associated with new imaging or pelvic examination evidence suggesting restriction or tethering of the pelvic tissues. Similarly, we will consider performing hysterectomy when there is a predominant uterine pain component by history and/or examination and the patient has exhausted a large number of other multimodal treatments. We also caution patients that hysterectomy may not relieve pain, may only partially relieve pain, and, in some cases, can worsen pain or cause a new pain that did not previously exist. (See 'Targeted therapies: Surgical' below.)
Patients whose pain resolves after targeted therapy require no further treatment. Those whose pain persists despite focused treatment are then treated as below. (See 'Baseline nonsurgical interventions' below.)
●For women with no identified cause or women whose symptoms do not resolve with targeted treatment – We consider CPP as originating from a somatic structure (eg, muscles, bone) or visceral organ (eg, uterus, ovaries, bladder, bowel) or as a pain amplification syndrome (ie, pain processing issue or neuropathic pain) in women with no identifiable peripheral cause or unresolved CPP in women whose pain does not improve despite therapies that target peripheral pain generators.
Some key principles that we and others follow in treating women with CPP of an undefined cause or persistent CPP despite treatment targeted to pain generators include the following:
•Ensure a thorough differential diagnosis, based on a detailed history and physical examination, has been developed prior to treatment (table 1 and table 2). This step is important to ensure that all potential relevant causes of a woman's pain have been explored.
-(See "Chronic pelvic pain in adult females: Evaluation", section on 'Initial evaluation'.)
•Avoid the reflexive use of surgical exploration prior to medical or nonpharmacologic therapy. Potential exceptions include women with acute unrelenting pain with signs of peritonitis, poorly controlled pain with a large adnexal mass or high suspicion for deep infiltrating endometriosis with obstructive symptoms, and women seeking to become pregnant imminently [1,2]. Some patients, when given the option of initial surgical therapy versus nonsurgical treatment, may express preference for surgery first; patient input is incorporated in choosing the initial therapy. Repetitive surgery for CPP is typically not helpful and could, in some cases, worsen the problem. (See "Chronic pelvic pain in adult females: Evaluation", section on 'Role of laparoscopy'.)
•Treat pain with a goal of regaining function. Similar to how we approach chronic musculoskeletal pain as described above, we generally employ a multimodal approach to the treatment of nonspecific CPP, as detailed below, that includes nonpharmacologic treatments such as physical therapy, use of medications in a tiered approach, targeted nerve blocks or cutaneous treatments, and empiric therapy with neuromodulators while incorporating principles of cognitive behavioral therapy and psychoeducational approaches [2,3]. We often will use both pharmacologic and nonpharmacologic therapies simultaneously. Each treatment approach is tailored to the goals of the individual patient and considers additional factors such as treatment cost and availability. Selective management of comorbid bladder and bowel issues (eg, bladder pain syndrome or irritable bowel syndrome) may be necessary as well. (See "Interstitial cystitis/bladder pain syndrome: Management" and "Treatment of irritable bowel syndrome in adults".)
•Preserve a positive outlook about each patient's prognosis. In our experience, positive expectations on the part of the clinician positively influence the treatment effect. In addition, protective associations have been demonstrated between positive patient affect and experimental pain sensitivity (ie, positive affect has been associated with reduced pain response) [4].
Importance of identifying, classifying, and treating neuropathic pain — The International Association for the Study of Pain defines neuropathic pain as "pain caused by a lesion or disease of the somatosensory nervous system" [5]. Commonly used symptom descriptions include "electric shock," "dull," "itching," and "burning." However, as sensory nerve function can also be altered in the absence of an identifiable lesion or disease, clinical guidelines suggest grading a presentation as "definite," "probable," or "possible" [6]. While the intensity of symptoms or categorization of the likelihood that pain is neuropathic does not translate to a validated, stepwise approach to treating these conditions, a reasonable strategy is to identify whether neuropathic pain is suspected to be acute versus chronic. The treatment of presumed neuropathic pain can be done in conjunction with the other treatment modalities discussed in this review.
We take the following approach:
●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. While there is no data-driven definition of acute neuropathic pain, most women present within days to weeks of the inciting event. In these cases, we aim 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, the risk-benefit balance generally favors a rapid return to the OR to attempt to remedy a nerve injury. One example is releasing the lateral lower quadrant laparoscopic fascial closure suture(s) following prior surgery performed in the ilioinguinal or iliohypogastric distributions (L1-2). Some clinicians will perform a steroid block (ie, nerve block) for pain in the pudendal nerve distribution following uterosacral vaginal vault suspension, and then proceed to surgery if the patient does not significantly improve in 48 to 72 hours. (See 'When to reverse prior procedure' below and "Nerve injury associated with pelvic surgery".)
•For women with mild symptoms following a procedure, or symptoms without an antecedent procedure, we typically prescribe centrally-acting neuromodulator agents (ie, antiepileptics, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors) along with anesthetic injections or topical anesthetics, such as a lidocaine patch. Any of the centrally acting agents listed below are appropriate choices for acute pain relief and are titrated to effect. (See 'Neuromodulators' below and 'Adjuvant therapies' below.)
●Chronic neuropathic pain – If the pain is more chronic in nature, such as three to six months duration or longer, we generally begin with a combination of nonpharmacologic therapy, a neuromodulator and possibly a nerve block. In addition, given the often refractory nature of long-standing neuropathic pain, modest improvement that is meaningful may be achieved by encouraging regular movement and mindfulness to avoid patient fixation on the pain site, which is akin to the approach in the trauma literature [7]. Evidence supporting late nerve release surgery for chronic neuropathic pain is lacking. (See 'Baseline nonsurgical interventions' below and 'Interventions for central sensitization or neuropathic pain' below.)
BASELINE NONSURGICAL INTERVENTIONS — For women with CPP of unidentified cause or that has not responded to targeted therapy, we offer pharmacologic and nonpharmacologic treatment simultaneously. We may employ these prior to offering a surgical treatment, or afterwards, based on the response. In some cases, treatment may be used for years, if not decades, if they improve quality of life. The rationale is that the optimal treatment or treatment combination for CPP is not known and this approach addresses the multifactorial nature of pain.
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 nonopioid medications [8]. We also use this approach as a baseline intervention in women with CPP because these medications are generally well tolerated, have few side effects and reasonable safety profiles, and are low cost. However, limited data are available in women with CPP, and many patients will have already attempted over-the-counter self-administration without meaningful response. We caution patients about exceeding recommended total daily doses to avoid acute gastritis and kidney or liver damage. In addition to the WHO analgesic ladder, we will often use muscle relaxants as initial therapy as well.
●Nonsteroidal anti-inflammatory drugs (NSAIDs) – NSAIDs are often used in the treatment of chronic pain as they are generally well tolerated, have a safer risk profile than opioid medications, and are low cost. In a meta-analysis of 13 trials assessing the impact of NSAID treatment on low back pain, NSAID use was more effective than placebo at reducing pain intensity scores as measured on a visual analog scale (VAS; mean difference -6.97, 95% CI -10.74 to -3.19, on a 0 to 100 VAS) [9]. NSAID use is well established in treating pelvic pain related to endometriosis. (See "Endometriosis: Treatment of pelvic pain", section on 'Nonsteroidal anti-inflammatory drugs'.)
Although many of our patients have tried an NSAID with insufficient response, we still discuss NSAID treatment to ensure that they have had an adequate trial of these medications, defined as an appropriate dose and frequency to achieve a treatment effect. Detailed reviews of the use and adverse effects of NSAIDs are presented elsewhere:
•(See "NSAIDs: Therapeutic use and variability of response in adults".)
•(See "NSAIDs (including aspirin): Pharmacology and mechanism of action".)
•(See "Nonselective NSAIDs: Overview of adverse effects".)
•(See "NSAIDs: Adverse cardiovascular effects".)
●Acetaminophen – While acetaminophen is indicated for the treatment of minor aches and pains, such as backache and muscular aches, it does not appear to be helpful for chronic pain syndromes [10]. That said, anecdotally, some women find acetaminophen use enhances the pain reduction achieved with other medication(s), such as NSAIDs (the drugs can be alternated). We educate patients about appropriate acetaminophen dosing to minimize risk of medication-induced hepatotoxicity. (See "Pharmacologic management of chronic non-cancer pain in adults", section on 'Acetaminophen'.)
●Topical analgesics – Although supporting data are mainly limited to studies of musculoskeletal injuries, joint pain, and postherpetic neuralgia, one small retrospective review reported at least some pain reduction in 11 of 13 patients (85 percent) using topical combination amitriptyline (1-2 percent) and ketamine (0.5 percent) for treatment of rectal, genital, or perineal pain [11,12]. The only adverse effect, occasional local irritation, was reported by one patient. Additionally, meta-analyses assessing the efficacy of topical diclofenac, ketoprofen, and high-dose topical capsaicin have reported efficacy for some chronic pain conditions, including osteoarthritis, postherpetic neuralgia, HIV-neuropathy, and diabetic neuropathy, but data on the treatment in women with CPP are lacking [13,14]. (See "Pharmacologic management of chronic non-cancer pain in adults", section on 'Acetaminophen'.)
●Muscle relaxants – Cyclobenzaprine is a skeletal muscle relaxant that is pharmacologically similar to tricyclic antidepressants. Use of cyclobenzaprine in women with CPP is based mainly on studies in patients with fibromyalgia. One systematic review reported improved sleep and pain symptoms and one small trial reported improved fatigue, tenderness, sleep and pain symptoms for cyclobenzaprine compared with placebo [15,16]. There are no efficacy data on cyclobenzaprine for treating pelvic pain symptoms. Drowsiness is common side effect, thus we recommend nighttime administration to improve tolerability and maximize sleep benefits. Similar medications include methocarbamol, metaxalone, carisoprodol, and tizanidine.
In our practice, we prescribe oral cyclobenzaprine 5 to 10 mg nightly. We then increase the frequency up to three times a day if the drug is helpful and does not cause significant sedation. An alternative option is oral tizanidine (regular release formulation), given as 2 to 4 mg three times a day, but this drug can also cause excess sedation. We limit routine use of carisoprodol because it can trigger acute euphoria, has been linked to potential abuse, and is metabolized into barbiturates, which can potentiate the effects of opioids.
Specific role of empiric hormonal therapy — One challenge in treating women with CPP of an unknown cause is deciding when to offer empiric hormonal treatment, typically with combined estrogen-progestin contraceptives (ie, pills, patch, or vaginal ring) or progestin-only contraceptives (pills, implant, injection, progestin intrauterine device) [17]. In our practice, we offer empiric hormonal suppression for women who have a cyclic exacerbation to their CPP. Continuous use of these agents is an effective therapy for menstrual cramping and pain as well as dysmenorrhea and may also alter how estrogen/progesterone circulating levels trigger inflammation or mediate sensitized pain pathways. They may also decidualize small superficial peritoneal endometriosis implants, if present. (See "Dysmenorrhea in adult females: Clinical features and diagnosis" and "Dysmenorrhea in adult females: Treatment".)
The use of hormonal therapy to treat diagnosed or presumed endometriosis is discussed in detail elsewhere. (See "Endometriosis: Treatment of pelvic pain", section on 'Medical treatment options' and "Endometriosis: Treatment of pelvic pain", section on 'Presumed endometriosis'.)
SUBSEQUENT TARGETED INTERVENTIONS — If the general treatments above prove ineffective, subsequent management is based on whether the dominant symptom or symptoms appear to come from a specific peripheral pain generator or whether the presentation is nonspecific; in the latter case, we focus on treatments that are more specifically thought to target central sensitization. For patients with symptoms that likely stem from a peripheral source, we offer therapies targeted at reducing pain generation, including physical therapy (PT), trigger point injections, nerve blocks, and surgical management. However, as central pain processing deficits can exist concurrently with peripheral pain generators, we address both peripheral and central sources of pain in women in whom targeted treatment alone is inadequate or ineffective. (See 'Interventions for central sensitization or neuropathic pain' below.)
Targeted therapies: Nonsurgical
Physical therapy — PT for CPP 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 [18]. In addition to the somatic intervention, physical therapists play an important role in comprehensive treatment of CPP because therapists often integrate pain education and cognitive-behavioral techniques such as mindfulness strategies alongside manual therapy [7]. (See "Myofascial pelvic pain syndrome in females: Pelvic floor physical therapy for management".)
Despite its widespread utilization as a primary mode of therapy for CPP, formal studies that evaluate the efficacy of PT for the treatment of CPP remain limited and are difficult to compare due to significant heterogeneity in therapy techniques and study design. Much of the presumed positive effect of PT is extrapolated from studies on other types of pelvic pain. In an observational cohort study of 374 men and women with myofascial pelvic pain syndrome (MPPS), 22 percent fewer patients reported using any pain medication at six months following treatment after learning to perform internal myofascial trigger point release using a therapy wand [19]. In a trial of 81 patients with painful bladder syndrome comparing pelvic floor PT with global therapeutic massage, patients receiving pelvic floor PT demonstrated a greater reduction in pain, urinary urgency, and frequency [20]. In a retrospective chart review of 124 patients with coccydynia, treatment with PT was associated with decreased mean average pain ratings (from 5.08 to 1.91) and mean highest pain ratings (from 8.81 to 4.75) on a 10-point visual analog scale [21]. (See "Evaluation of chronic non-cancer pain in adults", section on 'Pain severity and impact'.)
We believe that patients most likely to benefit from pelvic PT include those whose pain is reproducible on palpation or contraction of the pelvic floor or abdominal wall. We recommend referral to a physical therapist with expertise in pelvic floor PT for pelvic pain, as improved outcomes have been associated with therapists with specialized expertise [22]. The referral should specify that CPP is the indication for treatment and provide as much detail as possible regarding the suspected etiology of pain (eg, pelvic floor myofascial pain, low back pain, etc). Since many pelvic floor physical therapists focus their practice on the treatment of incontinence and prolapse, which often includes treatments to strengthen the pelvic floor, ideally the referring clinician should confirm the therapist is comfortable with the unique therapies necessary for the successful treatment of chronic pain conditions, since the treatments used for incontinence and prolapse can exacerbate pelvic pain.
Prior to initiating treatment, we advise women that PT may cause a temporary increase in pain, but this should decrease over the course of treatment. Individuals with a persistent increase in pain should be reevaluated for new conditions that may have developed since the last evaluation. We also discuss that PT often involves internal (vaginal) manipulation. Since not all patients feel comfortable with this approach, an experienced therapist can gradually address this issue and build up to this intervention as the clinician develops rapport and a therapeutic relationship with the patient. Finally, patients should expect to perform home exercises and stretches, and we discuss that adherence to the home therapy program increases the probability of long-term improvement in pain [23].
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 [24,25]. While these are a poorly understood and understudied cause of chronic pain, limited evidence suggests that trigger points are caused by abnormal neuromuscular depolarization [26-30] and are a common cause of myofascial pain conditions [24]. Evidence also suggests that trigger points may also directly contribute to the subsequent development of central pain amplification [26]. (See "Myofascial pelvic pain syndrome in females: Clinical manifestations and diagnosis", section on 'Trigger points'.)
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. Multiple studies support modest efficacy of trigger point injections for patients with CPP, often from myofascial pelvic pain [31-39]. We believe that patients most likely to benefit from trigger point injections are those with a relatively small focal area of pain, which is reproduced with palpation. Trigger point injections, in our experience, seem less effective in patients with widespread, diffuse pain, and clinicians should try to limit performing numerous, chronically repeated injections on a patient. Although there is no consensus regarding type or amount of anesthetic used in injections, the majority of studies have used either lidocaine or bupivacaine. Our clinical practice is to use 1 to 2 mL of 0.5% bupivacaine at each injection site using a 25 gauge needle. Some studies have added corticosteroids in injections, but this does not appear to improve outcomes [40] and is associated with risk for local muscle necrosis. Similarly, some practitioners will use dry-needling and attempt to mechanically alter muscle dynamics without any pharmacologic agent. Botulinum toxin injection, which is detailed below, may have a role in refractory cases as well; further details of trigger point injections are presented elsewhere. (See "Myofascial pelvic pain syndrome in females: Treatment", section on 'Trigger point'.)
Based on our clinical experience, we find the following issues worth considering when planning or performing trigger point injections:
●We consider patient habitus when choosing needle length, as it is important to inject past the fascia and into the muscle, but not into the abdominal cavity. Some obese women may require a spinal needle to reach the trigger point. However, in thin women, it is theoretically possible to injure intraabdominal visceral or vascular structures if using long (spinal) needles.
●If the area of pain is adequately anesthetized but pain improvement does not last for at least one day, in our experience, repeated injections are not likely to be beneficial. If the patient reports at least modest improvement with initial injection that lasts at least a few days to a week, we will often repeat injections in two to four weeks.
●When possible, injections should be repeated shortly after patient notes return of focal pain, with the goal of less frequent injections as pain improves. There are no evidence-based guidelines as to how often injections can be repeated or the maximum number of times injections can be performed. In our practice, we consider repeating injections in two to four week intervals up to a total of four to six injections if needed. If the patient has recurrence of pain, but had significant improvement for at least three months, (30 to 50 percent reduction), it is reasonable to offer a repeat series of injections.
Nerve block — Peripheral nerve blocks (PNB) are widely-used for surgical anesthesia as well as for both postoperative and nonsurgical analgesia. PNBs can also be used for diagnosis and treatment of nerve pain. In a patient with presumed nerve-related pain, a PNB that greatly reduces the pain supports the diagnosis and provides pain relief. For women with significant pain symptoms, PNBs can be combined with neuromodulators, although supporting data are limited. Peripheral nerve blocks are reviewed in detail separately. (See "Overview of peripheral nerve blocks".)
Photobiomodulation — A transvaginal near-infrared light therapy device (15 W diode laser that emits 810 and 980 nanometer wavelengths) has been approved for use in reducing muscle and nerve dysregulation in pelvic pain states, which may reduce the burden of physical therapy visits. The exact mechanism of photobiomodulation is not fully clear but may have to do with the energy transmission altering cellular nitric oxide concentrations. A multi-site uncontrolled case series of treatments using this therapy in females with a variety of pelvic pain conditions (mean age 44.3 ± 15.1 years) reported clinically meaningful reduction in pelvic pain in 59 percent of women who received at least five brief treatment sessions [41]. This encouraging initial result requires further confirmation with randomly assigned trials.
Targeted therapies: Surgical
When to operate for suspected pelvic pathology — 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 [eg, 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, or a stable longstanding uterine pain disorder, including refractory dysmenorrhea. In a retrospective review of 54 women with CPP who underwent surgery for suspected ovarian remnant syndrome or ovarian retention syndrome, approximately 40 percent of women reported at least 50 percent reduction in their pain [42]. Of note, women who reported a 30 percent or greater pain decrease had fewer additional diagnoses that were associated with pain compared with women who did not have such a pain reduction. The optimal timing to perform such procedures has not been established despite calls for research [43]. In addition, most available studies provide short-term information on pain relief, with only a few studies reporting more than a year's worth of follow-up data related to specific surgical intervention [44-46].
At times we consider performing surgery on women who do not have symptoms associated with the above pathology if multiple noninvasive therapies have not improved the pain. As an example, we have occasionally seen women with dramatic responses to simple myomectomy of small leiomyoma after two to three years of ineffective trials of empiric neuromodulator therapy and PT. In addition, select women with refractory chronic perineal (not pelvic) pain unresponsive to medical therapy, local injections, or PT may benefit from surgical pudendal nerve release. Candidates for this surgery, which is only offered by a small number of centers worldwide, generally are selected following the Nantes criteria, which need further validation [47]. (See "Female sexual pain: Differential diagnosis", section on 'Other conditions contributing to increased pain'.)
To optimize the chance that surgery will not further worsen pain sensitivity in a patient who potentially is already vulnerable, there is an urgent need to evaluate the role of enhanced recovery after surgery (ERAS) pathways for improving overall pain outcomes postoperatively. Challenges in studying the impact of ERAS programs include that outcomes are often institution specific and depend on the level of commitment given by the various teams in the pathway. In our practice, for almost all patients undergoing surgery, we use several preemptive medications to potentially reduce pain sensitization and the need for perioperative opioid administration. (See "Enhanced recovery after gynecologic surgery: Components and implementation".)
Treatment of endometriosis is covered in the following topics:
●(See "Endometriosis: Treatment of pelvic pain".)
●(See "Endometriosis: Surgical management of pelvic pain".)
●(See "Endometriosis: Long-term treatment with gonadotropin-releasing hormone agonists".)
When to reverse 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 nonpharmacologic therapy. However, we counsel women regarding the high rates of pain persistence despite procedure reversal or implant removal.
The efficacy of doing a procedure to remove a possible sensitizing foreign object for pain has only been described in uncontrolled small case series, with approximately 50 percent of women responding to conservative removal [48]. For women with synthetic mesh-related neuropathic pain, some authors suggest performing a full excision of the mesh if conservative treatments are ineffective, but these studies generally lack control groups and the total degree of pain improvement varies [49,50]. Studies are needed to determine the optimal candidates for surgical therapy, preoperative factors that predict successful surgical outcomes (eg, patient response to preoperative hypogastric nerve block or paracervical nerve block), and the necessary extent of surgery (eg, radical versus conservative surgery). (See "Transvaginal synthetic mesh: Management of exposure and pain following pelvic surgery".)
Pain associated with a foreign body may represent a nerve injury or sensitization. Examples include unexplained pain that develops following synthetic mesh insertion (such as for prolapse or incontinence) or following hysteroscopic insertion of tubal micro-inserts (commercial name Essure). Women with a history of prior chronic pain problems, including pelvic pain, low-back pain, headache, and fibromyalgia, appear to be at increased risk for persistent postprocedure pain [51]. It is unclear if this postprocedure pain represents persistence of preexisting pain versus new postoperative pain. Nerves that are particularly at risk for injury during gynecologic surgery include the ilioinguinal/iliohypogastric, genitofemoral, and the pudendal nerves. Localized pain that is reproducible on examination, particularly in the procedure/surgical region (eg, in the uterus or in the uterosacral ligaments), can be one clue when such history exists. These issues are presented in greater detail separately:
●(See "Hysteroscopic female permanent contraception", section on 'Pelvic pain'.)
●(See "Nerve injury associated with pelvic surgery".)
When to perform additional surgical procedures aimed to reduce pain — Women with CPP that is refractory to the above nonpharmacologic and medical therapies often ask about surgical options to reduce their pain. Potential procedures include presacral neurectomy, lysis of adhesions, and hysterectomy. Data supporting a role of these surgeries for the treatment of CPP are limited. For each of these surgeries, we counsel women about the risk of continued pain, and new postsurgical pain, in addition to the standard surgical risks.
●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. The main trial supporting this approach compared combined presacral neurectomy and surgical treatment of endometriosis with laparoscopic treatment of endometriosis alone for women with dysmenorrhea, and reported improved pain control with the combined approach (12 month cure rate: 86 versus 57 percent) [52]. Anecdotally, very few surgeons seem to employ this measure since it is primarily indicated for treating isolated central dysmenorrhea or chronic midline pelvic pain without associated symptoms of lateralized or pelvic floor pain. Having only central dysmenorrhea is relatively rare in our experience. Postoperative complications include a modest risk of chronic constipation and possible urinary retention [53].
●Lysis of adhesions – Routine lysis of adhesions does not appear to be helpful in treating CPP and therefore is not advised [18,54]. Although adhesions are commonly part of the differential diagnosis of CPP, the exact structural relationships (eg, connecting pelvic organs, entrapping specific nerve bundles) or mechanisms (eg, organ tethering) that would cause adhesions to contribute to cyclic or continuous pain are not well established. A trial of 100 patients (majority women) with chronic abdominal pain comparing laparoscopic adhesiolysis with sham laparoscopy reported similar reduction in pain scores for both groups (reduced approximately 20 out of 100 points at one year) [55]. Selective adhesiolysis, such as in the setting of a specific scar around an ovary or causing a hydrosalpinx that is consistent with the patient's pain pattern, may be appropriate but needs further study before being recommended routinely. We rarely perform adhesiolysis alone without a concomitant procedure. If, at the time of laparoscopy for other indications, such as during excision of endometriosis, we encounter an obliterated cul-de-sac, we will lyse adhesions in an attempt to normalize anatomy and will consider oophoropexy or uterine suspension to minimize the chance of the same scar recurring. (See "Endometriosis: Surgical management of pelvic pain", section on 'Adhesiolysis'.)
●Hysterectomy – We have proposed the phrase "chronic uterine pain" to describe individuals with the repeated finding of uterine tenderness on examination that does not respond to medical therapy and is not caused by endometriosis [56]. Certainly in some cases, symptomatic leiomyoma or adenomyosis, even when not markedly distorting the uterus, may be ultimately contributing to symptoms as well. We view these patients, where the diagnosis is not clearly defined by palpable pathology, as having a functional condition analogous to painful bladder syndrome or irritable bowel syndrome.
•Hysterectomy for pain indications – For those who have completed childbearing, hysterectomy can be a reasonable treatment option but may not alleviate all pain. Studies have reported continued pain symptoms in 5 to 38 percent of women following hysterectomy [57,58].
•Risk factors for continued pain – Preoperative factors associated with an increased risk of persistent pelvic pain include younger age, lack of pelvic pathology, depression, the presence of pain elsewhere in the body, and markers of central sensitization prior to hysterectomy [58]. In a prospective cohort study of 176 patients with pelvic pain, 12 percent of patients reported <50 percent improvement in pelvic pain six months after hysterectomy [59]. Every one-point increase in preoperative centralized pain score was associated with a 27 percent increase in the odds of persistent pelvic pain (odds ratio 1.27, 95% CI 1.03-1.57) six months after surgery [59].
•Overall benefit of pain reduction – It is important to note that even among the patients with high degrees of centralized pain prior to hysterectomy, most reported substantial improvement in their pain. Thus, we feel that the presence of central sensitization or other risk factors for persistent pain should not preclude surgeons from offering hysterectomy for the treatment of pelvic pain, but should be used to inform counseling on the risk of persistent pain, ensuring that treatments for other pain generators are maximized and planning for additional perioperative management strategies that target central sensitivity after hysterectomy if pain persists.
•Surgical considerations when performing hysterectomy
-Surgical route – We prefer laparoscopic hysterectomy when possible because it is associated with shorter recovery, less postoperative pain, and less blood loss (compared with open surgery), yet allows for intraabdominal evaluation and treatment of concomitant pathology, such as endometriosis. Additionally, the surgeon can evaluate for anatomic relationships that may have been distorted by prior surgery, such as the course of the ureters or the vesicouterine peritoneal fold.
-Bilateral oophorectomy – Concomitant ovary removal is generally only indicated in the setting of severe bilateral adnexal pathology (such as larger bilateral ovarian endometriomas) or genetic predisposition to cancer. Ovarian preservation avoids the long-term sequelae of surgical menopause [60]. Even among patients with endometriosis, bilateral oophorectomy may not sufficiently alleviate pain. For example, in population-based retrospective cohort study of nearly 4500 patients aged 19 to 50 years undergoing hysterectomy for endometriosis, patients who underwent bilateral oophorectomy had a lower rate of reoperation compared with those who had conservation of at least one ovary. However, the majority of reoperations in those with ovarian preservation were subsequent oophorectomy or lysis of adhesions. Furthermore, there was little difference in number of physician visits for endometriosis and pelvic pain, opioid use, and use of hormonal suppression medications after hysterectomy when comparing patients with ovarian preservation versus concomitant bilateral oophorectomy [61]. These findings suggest that persistent pain after hysterectomy may not differ significantly based on ovarian conservation status in most patients with endometriosis.
Less studied targeted treatments — There is some evidence supporting the use of vaginal anxiolytics and botulinum toxins for pelvic floor pain syndromes. However, more research is needed to determine the degree of efficacy before these treatments are routinely used.
●Vaginal anxiolytics – We occasionally use vaginal benzodiazepines as a temporary adjunct to facilitate pelvic floor PT only in very select patients, who are unable to tolerate pelvic floor PT, are warned about their side effects, and are screened to be of low risk for opioid misuse. We then wean the drug off once they complete a course of PT. (See "Myofascial pelvic pain syndrome in females: Treatment", section on 'Skeletal muscle relaxants'.)
Anxiolytic medications such as benzodiazepines have both muscle relaxant and anxiolytic effects, and, although not in favor to treat chronic pain because of risk of dependence and enhancement of opioid-mediated sedation, are used in some patients with bladder urgency and pain. Studies of vaginal diazepam suppositories, used as off-label therapy for patients with pelvic floor myofascial pain, have been associated with reduced symptoms of myofascial pelvic pain [62,63]. However, there is limited evidence supporting their use in idiopathic CPP. The mechanism of action for vaginal administration is unclear and likely involves some component of central effect. Gamma-aminobutyric acid (GABA) receptors have been characterized in the sensory dorsal root ganglion of rodents, which suggests these receptors might modulate ascending nociceptive input [64].
Of note, diazepam is systemically absorbed through vaginal mucosa and serum levels approach that of oral use [63]. Due to high serum concentrations through the vaginal administration, patients should be counseled that risk of dependency and abuse may be as likely as with oral administration. Benzodiazepines also potentiate opioid-related CNS depression, which increases risk for overdose. Therefore, we do not prescribe benzodiazepines for patients also receiving chronic opioid therapy. For women receiving opioid treatment, we prescribe 10 mg of baclofen, a skeletal muscle relaxant with some central nervous system depressant properties that also activates the GA17012454BA receptor, to be used by the vaginal route up to three times per day. (See "Pharmacologic management of chronic non-cancer pain in adults", section on 'Benzodiazepines'.)
●Botulinum toxins A and B – Although the supporting data are limited and include other forms of neuropathic pain, onabotulinum toxin A (BTXA) injections have been associated with reduced pain in some patients with CPP caused by refractory MPPS [65-70]. Data specific to patients with CPP are mixed, which may reflect different patient populations, variable injection dosing and/or location, study heterogeneity, and/or disease mechanisms.
•Botox helpful – A systematic review of 9 studies (two trials, five cohort studies, and two case series) reported clinically meaningful reductions in patient-reported pain scores 6 weeks after onabotulinum toxin injection that were still present at 12 months [71]. In a trial of women with CPP and pelvic floor muscle spasm comparing injections of BTXA with saline, both groups reported reduced dyspareunia and pelvic floor pressure, but only the BTXA group reported improvement in nonmenstrual pelvic pain [66].
•No benefit – A 2019 trial that randomly assigned 60 patients with MPPS to receive either 200 units of onabotulinum toxin or saline placebo reported similar outcomes for participant-reported pain (patient global impression of severity 63 versus 48 percent at three months, respectively), although both groups had high rates of pain at study onset, had been significantly pretreated with pelvic floor therapy, and also had concomitant PT during the trial [72]. In a systematic review of four studies (three trials and one comparative study) evaluating BTXA injections or placebo in 194 participants with gynecologic pelvic pain, pain scores at six months follow-up were similar for both groups [73]. However, given the small sample size, differences in the dose and method of injection and variability in time points for outcome measures, calculation of a summary estimate for treatment-related improvement was not possible and generalizability of the findings remains uncertain.
In our practice, we occasionally offer targeted BTXA of the pelvic floor given the low risk of adverse effects and possible benefit. However, we typically perform BTXA injection in women with pelvic floor spasm that is refractory to PT.
The use of BTXA for MPPS is presented in detail separately. (See "Myofascial pelvic pain syndrome in females: Treatment", section on 'Botulinum toxin'.)
INTERVENTIONS FOR CENTRAL SENSITIZATION OR NEUROPATHIC PAIN — For CPP that is unresponsive to targeted therapy or that is nonspecific, 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 (ie, neuromodulators). It is important to emphasize that the patient should continue to explore nonpharmacologic treatments that improve symptoms while simultaneously progressing through the various drug classes below.
Neuromodulators
General approach — In our 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 [18]. This list reflects our experience as well as the available literature and is not meant to be applicable to all women with CPP. We suggest beginning treatment with one anticonvulsant, tricyclic, or SNRI, the dose of which is slowly increased to a therapeutic range until the patient achieves consistent pain relief across the day. The choice of initial medication class is tailored to the patient's symptoms and other medical history. As an example, TCAs have simple, once daily dosing that makes them a good choice for patients who benefit from a simple dosing schedule. However, TCAs can be associated with constipation and cardiac side effects (tachycardia, arrhythmias) and thus are avoided in women with these issues or who develop these symptoms. There is no one-size-fits-all approach.
If the patient does not achieve pain reduction at a therapeutic dose, then we move on to the next class of drugs. Muscle relaxants can be used in combination with these medications for breakthrough pain. We select the drug that the patient is likely to best tolerate based on the medication's side effects. Subsequent changes are based on patient tolerance of any side effects and the impact of these side effects on lifestyle. For example, as all of these agents might cause dizziness, somnolence, or fatigue, they are not ideal for heavy machinery operators, and driving should be carefully monitored until levels are stable and the patient reports minimal to no somnolence or dizziness on the therapeutic dose.
Plans for pregnancy are an important consideration; these agents may not be the best choice for patients desiring to conceive. Anticonvulsants and TCAs cross the placenta and have been associated with adverse effects. The SNRIs have been associated with nonteratogenic effects in the newborn. For women on these medications who wish to conceive, we advise a consultation with a perinatologist to discuss risks to the developing fetus and newborn and to make a prepregnancy care plan. (See "Teratogenicity, pregnancy complications, and postnatal risks of antipsychotics, benzodiazepines, lithium, and electroconvulsive therapy".)
Anticonvulsants (gabapentin and pregabalin)
Review of data — The anticonvulsants gabapentin and pregabalin have demonstrated efficacy in treating other chronic pain syndromes and are both approved for the treatment of postherpetic neuralgia. Pregabalin is approved for the treatment of diabetic neuropathy and fibromyalgia [74,75]. (See "Pharmacologic management of chronic non-cancer pain in adults", section on 'Gabapentin and pregabalin'.)
However, conflicting data exist with regard to gabapentin for treatment of CPP in female patients. Potential explanations for the discrepant results below include study size, final dose of medication used, patient populations with incomplete characterization of overlapping pain conditions, and variable duration of treatment. The smaller trials reported benefit while the largest and adequately powered trial did not [76-78]. It is important to note that the adequately powered 2020 clinical trial that reported no reduction in pain symptoms assessed patients after 13 to 16 weeks of treatment and used a mean gabapentin dose of 2100 mg [78]. By contrast, the earlier but smaller studies that reported benefit followed patients for 6 to 24 months [76,77,79]. Representative global studies include the following:
●Benefit reported
•In a 2005 Austrian trial of 78 women with refractory CPP randomly assigned to treatment with gabapentin, amitriptyline, or combination, all patients reported improvement [76]. Both gabapentin groups reported a greater improvement in pain symptoms with lower incidence of side effects compared with those treated with amitriptyline alone. Study participants were evaluated before treatment and at 1, 3, 6, 12, and 24 months afterwards.
•The 2016 United Kingdom GaPP1 double-blind pilot trial randomly assigned 47 women with CPP and no obvious pelvic pathology to either gabapentin or placebo [77]. Women receiving gabapentin reported less pain (brief pain inventory difference 1.72 points, 95% CI 0.07-3.36) and improved mood (Hospital Anxiety and Depression Score difference 4.35 points, 95% CI 1.97-6.73) at six months [77]. Results from this pilot clinical trial were used to inform appropriate sample size, statistical analysis, recruitment, and retention for the GaPP2 trial reported below [78].
•A 2019 Egyptian trial comparing gabapentin with placebo in 60 women with CPP at least six months in duration and no obvious pelvic pathology reported reduced pain scores at 12 and 24 weeks in the gabapentin group compared with placebo [79]. While the magnitude of effect at 12 weeks was clinically small (mean visual analog scale in gabapentin groups was 5.12±0.67 versus 5.9±0.92 in the placebo group, p = 0.002), participants in the gabapentin group demonstrated further pain reduction at 24 weeks (3.72±0.69 versus 5.5±1.13, p<0.001). Similar to other clinical trials of gabapentin, participants taking the active drug reported a higher incidence of dizziness compared with placebo (26 versus 3 percent). The prespecified primary outcome of a 30 percent reduction in pain score was met by 95 percent of those on active treatment versus 35.7 percent of those receiving placebo. The dropout rates were particularly high in this study: 33 percent (n = 10) for the gabapentin group and 53.3 percent (n = 16) for the placebo group. Six of the dropouts in the gabapentin group were due to intolerable adverse effects (dizziness) while all women in the placebo group reported they left the study because of no improvement in symptoms, which suggests that participants may have been aware of study group assignment.
●No benefit reported – In an adequately powered 2020 multisite United Kingdom trial (GaPP2) that randomly assigned 306 female subjects with CPP at least three months in duration and no identifiable pathology on prior laparoscopy to gabapentin (n = 153) or placebo (n = 153), worst and average numerical rating scale pain scores were similar between the groups at 13 to 16 weeks from randomization, without clinically significant differences from baseline on average [78]. Dizziness was more common in the active treatment group (54 versus 26 percent), but a larger number of placebo recipients reported dizziness as well. This study, which was designed with significant patient input, included a four-week titration phase that started with a single gabapentin starting dose of 300 mg/day followed by a relatively rapid titration (dose increased by 300 mg every three days to a maximum dose of 9 capsules/day totaling 2700 mg). For comparison, the 2019 trial used a starting dose of 300 mg three times daily and increased the dose by 300 mg every seven days. In the GaPP2 study, women taking gabapentin reported more serious adverse events compared with those taking placebo (7 versus 2 percent). The authors concluded that gabapentin is not effective for CPP at a group level.
While the findings of the GaPP2 study add significant value and insight to the use of gabapentin for the treatment of CPP without obvious pelvic pathology, several issues need to be considered when applying these data to individual patients, including:
•Confounding of coexisting pain conditions – GaPP2 boasts extensive phenotypic details and secondary outcomes, unlike most clinical treatment trials for CPP. However, like many trials, the average duration of pain symptoms and the presence of many commonly overlapping pain conditions, such as pelvic floor myalgia or painful bladder, are not reported, which limits the ability to interpret results in these populations. More than three-fifths of the patients used opioid rescue medications (which suggests additional pain problems), all patients with irritable bowel syndrome were intentionally excluded, and bladder symptom questionnaires suggested a substantial proportion of enrolled participants likely suffered from bladder pain syndrome.
•Potential role in multimodal or bundled treatment – Despite the lack of effective treatments for patients with chronic pain syndromes as a group, some of these medications may prove useful for selected individuals as part of a panel of rapidly tested treatments, which is in fact how we often use this class of medications [80]. They also may prove more effective as part of bundled interventions, and indeed, gabapentin is used in single doses in the highly effective enhanced recovery after surgery protocols that demonstrate significant improvements in perioperative outcomes [81]. (See "Enhanced recovery after gynecologic surgery: Components and implementation".)
•Variation of individual pain response – While GaPP2's findings are highly informative, this study and most other highly controlled clinical trials examining the effectiveness of single treatments in patients with chronic pain remind us that careful phenotyping of patient characteristics and characterization of underlying pain mechanisms are needed to determine if there are subtypes of patients who are more likely to benefit from any given treatment option. Further analyses of these data and, possibly, additional studies are warranted to determine if certain subsets of patients benefit from gabapentin as part of a multimodal, interdisciplinary approach. For example, it is possible that in the early phase of the disease, in those with higher levels of pain intensity, those with co-occurring gastrointestinal symptoms suggestive of irritable bowel syndrome, and those who seem to manifest symptoms of central sensitization (such as widespread pain and fatigue) may be subsets of patients who are more likely to experience meaningful pain improvement.
Approach to anticonvulsant dosing — Despite conflicting data and an adequately powered trial reporting lack of impact (as reviewed above), we continue to prescribe oral gabapentin (capsule or tablet) for a limited number of appropriately counseled patients as part of a multimodal, interdisciplinary treatment approach. We routinely discuss with our patients that dizziness, impaired cognition, and excess sedation may occur with use of any neuromodulator and may be intolerable. The approach outlined below is based on the available data and our clinical experience:
•If the patient is of normal body weight and does not report substantial issues with fatigue, we generally prescribe a starting dose of 300 mg once a day and titrate up by 300 mg/day every five to seven 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 [82].
•In our experience, women who are postmenopausal, in the low range of body mass index (BMI), or who describe themselves as very sensitive to medication side effects often do better by starting with smaller starting doses, such as 100 mg at bedtime, then increasing the dose as needed and as tolerated by 100 mg every one to five days, and then gradually increasing to 300 mg three times per day. Since some women will report a symptom improvement at lower doses, we give women written instructions on how to slowly increase the dose until they feel improvement in pain (going up to a maximum dose of 900 mg three times per day). The dose may be increased further, depending on the patient's symptoms and ability to tolerate side effects.
•The maximum tolerated dose in long-term clinical trials appears to be approximately 2700 to 3600 mg per day in divided doses. In a multicenter trial of patients with fibromyalgia, the median dose was 1800 mg per day, with a range of 1200 to 2400 mg per day [83]. It may take one to two weeks to observe an effect with each dose change. The dose is ideally tapered down slowly in a similar fashion over several days before it is discontinued. (See "Pharmacologic management of chronic non-cancer pain in adults", section on 'Gabapentin and pregabalin'.)
●Pregabalin – When prescribing pregabalin, we begin with oral capsules of 50 to 75 mg given two to three times a day. We base the choice of dose and frequency on the patient's severity of pain, with higher and more frequent doses used in patients with more severe symptoms. As with gabapentin, many women will have a symptom response at lower doses, and thus, we give women written instructions on how to slowly increase the dose until they feel relief (going up to a total dose of 450 mg daily). It may take a few days to observe an effect. Ideally, the dose is tapered down slowly in a similar fashion over at least seven days before it is discontinued to avoid possible symptoms, including insomnia, nausea, headache, anxiety, hyperhidrosis, and diarrhea [84]. (See "Pharmacologic management of chronic non-cancer pain in adults", section on 'Gabapentin and pregabalin'.)
Tricyclic antidepressants (TCAs) — TCAs are often considered first-line treatment of centralized pain conditions, although older meta-analyses reported a limited effect in treating neuropathic pain, presumably because the available trials included small sample sizes and poor study designs [85-87]. (See "Pharmacologic management of chronic non-cancer pain in adults", section on 'Tricyclic antidepressants'.)
●Mechanism of action – TCAs inhibit reuptake of serotonin and norepinephrine, thereby increasing the amount of available norepinephrine and serotonin [88]. 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. As TCAs block muscarinic M1, histamine H1, and alpha-adrenergic receptors, they can also cause cardiac effects, anticholinergic effects, antihistaminic effects, decreased seizure threshold, sexual dysfunction, diaphoresis, and tremor. (See "Tricyclic and tetracyclic drugs: Pharmacology, administration, and side effects", section on 'Side effects'.)
●Supporting data – Although amitriptyline is one of the most widely used agents in treating other neuropathic pain syndromes, information on its use in the treatment of CPP is sparse but trends toward being helpful, as highlighted in reviews of chronic pain treatment [76,89,90].
•Trial for bladder pain – Its wide usage prompted a multicenter placebo-controlled trial in a predominantly female interstitial cystitis/painful bladder syndrome cohort previously naïve to therapy [89]. The trial failed to show superior efficacy of amitriptyline largely because 47 percent of the placebo group reported moderate to marked improvement at 12 weeks of therapy (versus 55 percent of the treatment group). The investigators did report an additional statistically significant effect in post hoc analysis of the cohort that could tolerate doses of 50 mg or higher. This study recruited treatment-naïve patients and had high rates of response in both placebo and active treatment groups. Although the authors did not conclude that amitriptyline is ineffective for CPP despite the absence of significant findings, caveats to the routine use of amitriptyline, similar to those for gabapentin, are probably warranted. (See 'Review of data' above.)
●Approach to dosing for CPP – We prescribe oral amitriptyline, 10 to 25 mg at night, if the patient is of normal weight and does not report substantial issues with fatigue. Nortriptyline (similar dosing strategy) in our experience may be better for those with more susceptibility to sedation or constipation. (see below).
•Starting dose – While amitriptyline dosing is not based on the patient's weight, in our practice, we have found that higher doses cause excessive sedation in very thin women. Therefore, we start very lean women on a 10 mg dose and increase the medication as tolerated. We use the 25 mg dose for younger patients of normal weight. Older patients may need an electrocardiogram to make sure they do not have an underlying arrhythmia.
•Dose titration – We start at lower doses and increase the dose as needed by 10 to 25 mg weekly, until symptoms are adequately controlled, to a maximum dose of 150 mg daily [91]. Many women will have pain relief at lower doses and will not reach 150 mg; we give women written instructions on how to slowly increase the dose until they feel relief and do not have intolerable side effects. It may take one to two weeks between dose changes to observe an effect.
Amitriptyline may not be well tolerated due to the anticholinergic side effects of fatigue, dizziness, dry mouth, and constipation. Secondary amine tricyclics, including nortriptyline and desipramine, have fewer anticholinergic side effects and are often better tolerated but may be less effective than amitriptyline [92]. Side effects may be mitigated by slowly titrating the dose and nighttime administration. For patients who wish to stop the drug, the dose is tapered down slowly in a similar fashion over several days before it is discontinued.
Detailed discussions of TCA use in treating pain and TCA discontinuation are presented separately.
•(See "Discontinuing antidepressant medications in adults", section on 'Tricyclics'.)
Serotonin norepinephrine reuptake inhibitors (SNRIs) — SNRIs, such as duloxetine, venlafaxine, milnacipran, and desvenlafaxine appear to increase centrally available serotonin and norepinephrine. These drugs are approved for the treatment of diabetic neuropathy (duloxetine and venlafaxine) and chronic musculoskeletal pain (eg, fibromyalgia, milnacipran) based on studies demonstrating improvements in pain and quality of life measures [93,94]. While SNRIs are generally well tolerated, side effects can include dry mouth, dizziness, fatigue, constipation, difficulty sleeping, and decreased appetite. (See "Pharmacologic management of chronic non-cancer pain in adults", section on 'Serotonin-norepinephrine reuptake inhibitors'.)
●Extrapolated efficacy data – While data specific to female CPP are limited, use of these drugs can be extrapolated from trials evaluating other chronic and neuropathic pain syndromes, as highlighted in a recent review of systematic reviews [90,95]. A small, comparative, unblinded trial suggested improved male CPP with the addition of duloxetine to an existing drug regimen and a systematic review of venlafaxine for other types of neuropathic pain reported reduced pain when compared with placebo [96,97].
●Our approach – We have the most experience with duloxetine and begin CPP patients on 30 mg daily (as with fibromyalgia or chronic musculoskeletal pain) and then increase to 60 mg daily after one week. We educate women that it may take a few days to observe an effect. Before discontinuing the medication, the dose is tapered down slowly over several days before it is discontinued in order to avoid withdrawal symptoms. Duloxetine should be avoided in patients with hepatic or severe renal insufficiency. (See "Discontinuing antidepressant medications in adults".)
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 the spontaneous firing of sensory neurons [98]. Among patients with chronic low-back pain, one trial reported topiramate resulted in improvement in pain and health-related quality of life with the added benefit of modest weight loss [99]. One study of 31 women with chronic vulvar pain reported reduced pain and improved mood compared with baseline measurements after eight weeks of lamotrigine treatment [100]. Data for use in women with idiopathic CPP are lacking. We have mainly used topiramate in this group, which is also used frequently for migraine headaches. Dosing can start at 50 mg twice a day and be titrated up to 200 mg twice a day, but patients must watch for cognitive impairment in addition to sedation. (See "Pharmacologic management of chronic non-cancer pain in adults", section on 'Antiseizure medications'.)
Nonpharmacologic therapies — Nonpharmacologic strategies, including exercise, peripheral neuromodulation, and cognitive behavioral therapy, can be used in conjunction with pharmacologic or surgical therapy. Physical therapy, described above, may promote better movement with some benefit even in individuals who do not have specific findings. These also may have roles in improving dysregulated pain processing systems. (See 'Physical therapy' above.)
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 [101]. CBT can be highly effective therapy for multiple chronic pain conditions [102-105], and research regarding CBT for the treatment of CPP suggests a positive impact, although the body of evidence is limited [106]. In our experience, patients tend to have either a significant response or none at all. However, as CBT carries low risk and nearly every patient with chronic pain can benefit from some aspect of CBT, we recommend this treatment to any patient who reports CPP of long duration and/or those who report substantial mood symptoms, disrupted sleep patterns, dysfunctional relationships, or avoidance of physical activity or work due to pain. (See "Overview of psychotherapies", section on 'Cognitive and behavioral therapies' and "Approach to the management of chronic non-cancer pain in adults", section on 'Psychological therapy'.)
Based on our experience, we discuss the following with women whom we refer to CBT:
●It is very important that the provider explain why this treatment is recommended. Many patients with CPP feel that providers who recommend CBT think that their pain is "all in their head." We educate patients that chronic pain frequently has a negative impact on mood, sleep, activity, and other aspects of quality of life, and reassure them that CBT helps to modify the thoughts and behaviors that exacerbate pain.
●Cognitive behavioral therapists that specialize in chronic pain are not widely available, often have long wait times for new patients, and their services are often not covered by many health care plans. We suggest clinicians caring for women with CPP contact social workers and psychiatrists in their community, as these providers may have referral recommendations.
●If in-person CBT is not available or feasible, we discuss that internet-based or app-based CBT programs may be helpful, as these programs may be more accessible to the patient. A systematic review of 15 internet-based psychological therapy programs for chronic pain conditions concluded that the internet-based programs were equally effective as traditional CBT [107].
Exercise — Exercise interventions appear to be helpful for a variety of chronic pain conditions [108], including CPP [109-111] and dysmenorrhea [112-115]. Improvements have been reported in pain, quality of life, physical function, mood, sleep, and self-efficacy. Nearly every patient can benefit from exercise, regardless of baseline health status, etiology of CPP, or comorbid pain or medical conditions. Physical activities that are beneficial are varied, and may include walking, aerobic, strength training, yoga, Pilates, and swimming. In a small trial including 60 women with CPP comparing conventional therapy with conventional therapy plus yoga, the women in the yoga group reported a decreased in pain intensity and increase in quality of life after 8 weeks of intervention [110]. Similarly, in a meta-analysis of 12 trials comparing yoga with no exercise in patients with chronic low-back pain, the yoga group had improvement in back-related function, and possibly reduced pain at three and six months of follow-up [116].
We encourage any activity that a patient enjoys and can adapt to her individual schedule and lifestyle. We advise women to pace themselves and set reasonable expectations (ie, "start low, go slow"). In addition, we counsel patients to utilize a regimen that begins with a regular, low-intensity, short-duration activity. Intensity and duration can then slowly increase as the patient develops more strength and endurance. We also advise women to avoid starting with a high-intensity exercise regimen as this approach is likely to exacerbate pain and is often not-sustainable, thus increasing the probability that patients abandon exercise altogether.
Nonpharmacologic therapies of less clear benefit
●Acupuncture – Acupuncture includes needling, auricular point manipulation, and moxibustion (warm acupuncture) [117]. While the available evidence is mainly limited to one study in women with endometriosis-related pelvic pain, acupuncture was associated with reduced dysmenorrhea [118]. In a systematic review that included 134 studies of acupuncture or dry needling (no anesthetic injection) for management of myofascial trigger point pain, there was a trend toward treatment efficacy, but major differences in study design, quality, and size limited the ability to analyze combined data [119]. 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 [120]. Use of these modalities for women with CPP is mainly extrapolated from data on other pain syndromes. In our practices, only a small handful of patients are referred for neuromodulation when they have high-intensity pain that is refractory to traditional therapy; the data for peripheral neuromodulation in treating CPP are limited and mostly from other types of pain disorders.
TENS has been associated with reductions in myofascial and low-back pain [121,122]. PTNS, which is considered a third-line therapy for overactive bladder, may also have efficacy in treating CPP, as demonstrated by two small trials reporting improvements in pain, physical function, fatigue, emotional role, and social functioning when compared with usual care [123-125]. Interestingly, one of these studies demonstrated sustained efficacy for at least six months after therapy [125]. SNM is considered a third-line treatment for overactive bladder by the American Urologic Association [123] and has off-label use as a fourth-line treatment of bladder pain syndrome (BPS) [126]. While observational cohort studies report reductions in pain, urgency, and frequency in patients with BPS treated with SNM, there are no trials in women with CPP [127]. Regarding pudendal neuromodulation, a small single-cohort pilot study of pudendal neuromodulation in 19 patients with pudendal neuralgia, 84 percent reported significant improvement in pain [128]. (See "Approach to the management of chronic non-cancer pain in adults".)
●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, but data regarding their use for CPP in women are limited and contradictory [129-131]. As examples:
•Endometriosis – One cohort trial in women with endometriosis-related pain reported significant improvements in pain symptoms after 12 months of gluten-free diet [132]. A small trial comparing postoperative hormonal therapy with dietary therapy in women who underwent conservative surgery for stage III to IV endometriosis reported that both postoperative hormonal suppression and dietary supplementation were equally effective in reducing nonmenstrual pelvic pain and both resulted in improved quality of life compared with placebo [133]. In this trial, the dietary protocol consisted of limited nutritional intake (range 1600 and 2000 calories per day) in addition to vitamins (B6, A, C, E), minerals salts (Ca, Mg, Se, Zn, Fe), VSL3 lactic ferments (Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus bulgaricus, Streptococcus thermophilus), and omega-3 and omega-6 fatty acids (fish oil), individualized to each woman based on her BMI, physical activity level, and type of job. This approach can offer benefit to those with unknown or other causes of CPP, but formal studies are needed.
•Dysmenorrhea – A meta-analysis of 27 trials evaluating the impact of dietary supplements for patients with dysmenorrhea did not find evidence for significant symptom improvement across multiple vitamins, minerals, botanicals, or foods, while a different meta-analysis of observational and interventional studies reported that supplementation with omega-3 polyunsaturated fatty acids improved chronic pain, mainly due to reductions in dysmenorrhea [134,135].
We emphasize that, unless someone has dramatic initial improvement in symptoms with a restrictive or altered dietary regimen, it seems unwise to drastically eliminate food groups, particularly fruits and vegetables, from the usual diet based on the limited available data. Different types of restrictive diets are presented in detail separately. (See "Treatment of irritable bowel syndrome in adults", section on 'Dietary modification'.)
Adjuvant therapies — These approaches are not used widely but have been reported. We advise further evaluation of these treatments in women with CPP before routine use.
●Antipsychotic medication – While one meta-analysis of 11 trials comparing oral antipsychotic medication with placebo or other treatment for acute or chronic pain in adults reported a reduction in mean pain intensity (relative risk 0.43, 95% CI 0.25-0.73), use of these medications is inherently limited by extrapyramidal side effects (eg, involuntary movements, parkinsonism, and akathisia) and sedating effects [136]. That said, a trial of an antipsychotic medication, in conjunction with a provider experienced in monitoring use of these medications, might be considered for women who continue to have inadequate pain control on the established therapies discussed above.
●Cannabinoids – Although many patients request guidance on use of cannabinoids, supporting data are limited and often based on studies at high risk of bias. For example, a systematic review concluded that most of the surveyed women reported reduced gynecologic pain with cannabis use, but we do not have confidence in the estimates of effect because of [137]:
•Likely bias inherent in retrospective survey studies (which represent half of the included studies)
•Grouping of multiple endocannabinoid-associated effectors (enhancers of endogenous cannabinoids [palmitoylethanolamide] or fatty acid amide hydrolase inhibitors as opposed to direct prospective assessments of phytocannabinoids)
•Heterogeneity of included pelvic pain diagnoses, cannabis delivery methods, and doses of cannabis
•Small sample sizes and lack of placebo-controlled data
The available data do not confirm efficacy or safety of cannabinoids, cannabis, or endocannabinoid modulating compounds in the management of pelvic pain. One exception may be palmitoylethanolamide as one randomized controlled trial included in the systematic review reported treatment efficacy.
The Canadian Pain Society recommends cannabinoids as third-line treatment for chronic neuropathic pain, following use of first-line (gabapentinoids, TCAs, and serotonin noradrenaline reuptake inhibitors) and second-line (tramadol and controlled-release opioids) agents [138]. As access to cannabinoids is legally restricted in many areas, we do not have clinical experience with this treatment.
Use of cannabinoids for the management of non-cancer pain is discussed elsewhere. (See "Pharmacologic management of chronic non-cancer pain in adults", section on 'Cannabis and cannabinoids'.)
Therapies to consider cautiously — As opioid therapy has not been clearly demonstrated to improve neuropathic pain and carries the risk of addiction, we do not prescribe opioid medication for long-term maintenance therapy in women with CPP [18,139-141]. We will prescribe brief courses of opioids postoperatively or to use as a bridge to surgery for women with significant pain symptoms and resultant loss of function in whom a likely cause has been identified (eg, deep infiltrating endometriosis, leiomyoma, or adnexal pathology).
●Opioids – For postoperative pain or brief pain flares, we typically prescribe the short-acting opioids hydrocodone or oxycodone (with or without acetaminophen) in 5 mg oral doses every six hours as needed. For patients who do not tolerate hydro- or oxycodone, alternate opioid options include pure synthetic opioids like tapentadol (commercial name Nucynta, 50 to 100 mg orally every six hours) or oxymorphone (commercial name Opana IR, 5 mg orally every six hours). Extended-release opioids are not recommended for acute pain, including postsurgical pain, because of potential for addiction [142].
●Tramadol – An additional treatment option is tramadol (50 mg orally every six hours), which is both a combined µ-opioid agonist and norepinephrine and serotonin reuptake inhibitor [143]. Tramadol should be cautiously used with other selective serotonin uptake inhibitors, with monitoring if used for a prolonged period, as it can rarely result in serotonin syndrome. In addition, it has been linked with a low but increased risk of seizures when administered concomitantly with TCAs.
RESOURCES FOR PATIENTS AND CLINICIANS
●International Pelvic Pain Society – A nonprofit organization dedicated to the diagnosis and treatment of women with CPP that provides patient education materials and resources for clinicians.
●The International Association for the Study of Pain information from special-interest groups (SIGs) focused on specific types of pain.
●American College of Obstetricians and Gynecologists FAQ sheet – A free handout that answers questions about CPP.
●The Society of Obstetricians and Gynaecologists of Canada provides consensus guidelines for the management of pelvic pain.
●FibroGuide is a highly effective web-based cognitive behavioral therapy-interactive program from the University of Michigan Chronic Pain & Fatigue Research Center that is available to the public at no cost [144]. While it is designed specifically for the patient with fibromyalgia, most modules are applicable to almost any chronic pain condition, and many of our CPP patients have found it to be a helpful resource.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Female pelvic pain".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Chronic pelvic pain in females (The Basics)")
●Beyond the Basics topics (see "Patient education: Chronic pelvic pain in females (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●General approach – The optimal approach to the management of chronic pelvic pain (CPP) of unclear etiology is uncertain, in part because the field of CPP lacks well-designed, large volume trials with appropriate longitudinal follow-up to validate existing treatments and in part because pain is an end symptom of diverse etiologies (table 1). (See 'Is there a probable versus unidentified cause of CPP?' above.)
•Probable etiology – For females with CPP associated with a probable peripheral etiology, initial treatment is aimed at addressing the presumed cause (eg, treatment of endometriosis, pelvic floor dysfunction, painful bladder syndrome, or irritable bowel syndrome) (table 1). Individuals whose pain resolves require no further treatment. (See 'Is there a probable versus unidentified cause of CPP?' above.)
•Unidentified cause or persistent pain – For females with CPP without an identified cause or that persists despite targeted therapy, we view CPP as originating from a somatic structure (eg, muscles, bone) or visceral organ (eg, uterus, ovaries, bladder, bowel), or as a pain amplification syndrome (ie, pain processing issue or neuropathic pain). We consider treatment of central pain amplification, simultaneously offering therapy that may include both pharmacologic and nonpharmacologic treatments. (See 'Is there a probable versus unidentified cause of CPP?' above.)
●Baseline treatments – For females with CPP of unclear etiology or whose CPP persists despite targeted treatment, baseline nonsurgical treatment options include nonsteroidal anti-inflammatory drugs, acetaminophen, topical analgesics, muscle relaxants, and, in some cases, empiric hormonal therapy. Treatments may be used for years, if not decades, if they improve quality of life. The rationale for this approach is that the optimal treatment or treatment combination for CPP is not known, and this approach addresses the multifactorial nature of pain. (See 'Baseline nonsurgical interventions' above.)
●Subsequent targeted interventions – For women whose pain persists despite baseline interventions, subsequent therapy includes both nonsurgical and surgical treatments targeted at peripheral pain generators, if such pain generators are identified during the history and physical examination. (See 'Subsequent targeted interventions' above.)
•Nonsurgical – Targeted nonsurgical treatments include physical therapy, trigger point injections, and nerve blocks. (See 'Targeted therapies: Nonsurgical' above.)
•Surgical – Targeted surgical treatment is reasonable when there is a high clinical suspicion for conditions that will likely respond to surgery. Examples include suspicion for deep infiltrating endometriosis, a reversible process iatrogenically caused by a prior procedure, focal pain that is reproduced with palpation of a leiomyoma, chronic adnexal pathology, or a stable longstanding uterine pain disorder, including refractory dysmenorrhea. (See 'Targeted therapies: Surgical' above.)
•Additional treatment modalities – There is some evidence supporting the use of vaginal anxiolytics and botulinum toxins for pelvic floor pain syndromes. However, more research is needed to determine the optimal approach to therapy and degree of efficacy before these treatments are routinely used. (See 'Less studied targeted treatments' above.)
●Interventions aimed at central sensitization of pain – For CPP that is unresponsive to targeted therapy or that is nonspecific, the field of pain medicine accepts a hypothetical significant role for altered central pain processing (ie, central sensitization), and widely employs medications (ie, neuromodulators) that alter circulating levels of neurotransmitters thought to underlie that imbalance. It is important to emphasize that the patient should continue to explore nonpharmacologic treatments that improve symptoms while progressing through the various drug classes below. (See 'Interventions for central sensitization or neuropathic pain' above.)
•Common medications – In our practice, neuromodulator treatments include anticonvulsants, tricyclic antidepressants, and serotonin norepinephrine reuptake inhibitors (SNRIs) because of their demonstrated efficacy, tolerability, and relatively safe side effect profile. This list reflects our experience as well as the available literature and is not meant to be applicable to all women with CPP. We suggest beginning treatment with one anticonvulsant, tricyclic, or SNRI, the dose of which is slowly increased to a therapeutic range until the patient achieves consistent pain relief across the day. The choice of initial medication class is tailored to the patient's symptoms and other medical history. (See 'General approach' above.)
•Nonpharmacologic treatments – Nonpharmacologic strategies, including exercise, peripheral neuromodulation, and cognitive behavioral therapy, can be used in conjunction with pharmacologic or surgical therapy. Physical therapy in some individuals, even without targeted findings, may promote better movement with some benefit. These also may have roles in improving dysregulated pain processing systems. (See 'Nonpharmacologic therapies' above.)
•Adjuvant medication – Adjuvant medications, including antipsychotics and cannabinoids, are not widely used, but have been reported. We advise further evaluation of these treatments in women with CPP before routine use. (See 'Adjuvant therapies' above.)
•Avoidance of opioids – As opioid therapy has not been clearly demonstrated to improve neuropathic pain and carries the risk of addiction, we do not prescribe opioid medication for long-term maintenance therapy in women with CPP. We will prescribe brief courses of opioids postoperatively or to use as a bridge to surgery for women with significant pain symptoms and resultant loss of function in whom a likely cause has been identified (eg, deep infiltrating endometriosis, leiomyoma, or adnexal pathology). (See 'Therapies to consider cautiously' above.)
ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledge Fred Howard, MD, who contributed to an earlier version of this topic review.
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