Chronic pelvic pain is defined as continuous or intermittent pelvic pain of longer than 6 months duration. No symptoms uniquely identify genitourinary structures as a source of pelvic pain. Even the relationship of recurrent pain to menstruation or the presence of dyspareunia is only suggestive.

Annually, 400,000 laparoscopies are performed on patients with endometriosis and chronic pelvic pain. Negative laparoscopic findings occur in 40% of patients.

Important nongynecologic causes that must be considered in the differential diagnosis include irritable bowel syndrome (IBS), Interstitial cystitis (IC), and pelvic floor myofascial syndrome. Importantly, rule out abdominal wall etiologies that are aggravated by raising of the head or raising of straightened legs while supine.

Dyspareunia as a significant factor

Patients with deep, internal, or thrust dyspareunia often express a feeling that some sort of internal collision is occurring during sexual activity. Any pelvic pathology may be responsible for this discomfort, but abnormalities such as endometriosis, pelvic adhesions, pelvic relaxation, malposition (retroversion), adnexal pathology or prolapse, and uterine fibroids are the most likely causes. IC may cause dyspareunia before it proceeds to chronic unremitting pain. IBS may also cause dyspareunia and pain at the apex of the vagina.

Adhesions

A recent study using conscious pain mapping during awake laparoscopy found that peritoneal adhesions and filmy adhesions that allowed for movement between 2 structures had the highest pain scores, while dense, fixed adhesions caused less pain. Pain is acyclical and not accompanied by vaginal bleeding. Dyspareunia and symptoms suggestive of intermittent subacute bowel obstruction may be associated with adhesions. Adhesiolysis should be recommended with realistic expectations, and a multidisciplinary approach in a pain clinic may be worthwhile prior to attempting surgery. In one study, cure or improvement was reported in two thirds of patients with chronic pelvic pain and nearly half of those with dysmenorrhea.

In a randomized study, patients with severe adhesions involving the intestinal tract were shown to benefit from adhesiolysis. A recent study found adhesions deflecting the sigmoid colon to the pelvic sidewall in 38% of patients with chronic pelvic pain. Among patients without detectable endometriosis, 80% had a significant reduction in symptoms after adhesiolysis on an 18-month follow-up. Various agents have been reported to reduce adhesion formation, but none have gained universal acceptance. A recent small randomized study of 25 patients found a significant improvement in right-sided pain in women who underwent paracolic adhesiolysis.

Chronic pelvic inflammatory disease

Pain is thought to be due to infection or adhesions that exacerbate the baseline condition. However, a recent animal study failed to show adhesions following direct bacterial inoculation. Infection may be accompanied by fever, leukocytosis, and gonococcal or chlamydial infection. Laparoscopy and peritoneal fluid cultures help confirm the diagnosis in most cases. Empiric treatment with antibiotics should be commenced prior to laparoscopy.

Ovarian remnant syndrome

Following a total abdominal hysterectomy and bilateral salpingo-oophorectomy, the ovarian remnant can undergo cystic changes that cause pain. Hormonal suppression with danazol, combined oral contraceptive pills, high-dose progestins, and GnRH agonists are possible treatment options. Diagnosis may be aided by ultrasonography. Laparoscopy is often fruitless because of the density of adhesions, and a laparotomy is the surgical procedure of choice for tissue removal. Finding the ovarian tissue may be challenging.

Irritable bowel syndrome

IBS is one of the most common functional intestinal disorders. It is defined as a group of functional disorders in which abdominal discomfort or pain is associated with defecation or a change in bowel habits. IBS also involves features of disordered defecation.

Rome criteria for IBS

Recurrent symptoms (2 of 3) present for at least 12 weeks in the preceding year

•   Abdominal pain relieved with defecation
•   Onset associated with change in frequency of stool
•   Onset associated with change in stool appearance

Symptoms supportive of diagnosis

•   Abnormal stool frequency
•   Abnormal stool form
•   Abnormal stool passage
•   Passage of mucus
•   Bloating

History plays an important role in excluding causes such as lactose intolerance, which present with similar symptoms. Upon examination, a tender sigmoid colon is often palpable. Fiber supplementation has not been shown to have significant benefits and should be reserved for patients with hard stools. Patients with recurrent severe abdominal cramps may benefit from antispasmodics such as dicyclomine and hyoscyamine, although this treatment has not been substantiated in controlled studies. Patients with severe IBS need a multifaceted approach that includes psychiatric evaluation because symptoms may be a part of a somatization disorder.

Low-dose antidepressants such as amitriptyline and selective serotonin reuptake inhibitors may have an adjunctive role. Alosetron (Lotronex) has been reintroduced to the US market and is approved for severe chronic diarrhea-predominant IBS, but only after other treatment modalities are unsuccessful, because of the risk of serious adverse gastrointestinal events (eg, ischemic colitis, serious complications of constipation). These adverse effects have resulted in hospitalization, blood transfusion, surgery, and death.

Tegaserod (Zelnorm), which is a partial agonist of the 5-hydroxytryptamine receptor that helps symptoms of IBS, alleviates constipation and accelerates intestinal transit. A recent meta-analysis found tegaserod to have significant benefits in women with constipation-predominant IBS.

Tegaserod was temporarily withdrawn from the US market in March 2007; however, as of July 27, 2007, restricted use of tegaserod is now permitted via a treatment IND protocol. The treatment IND will allow tegaserod treatment of irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC) in women younger than 55 years who meet specific guidelines. Its use is further restricted to those in critical need who have no known or preexisting heart disease.
Earlier this year, tegaserod marketing was suspended because of a meta-analysis of safety data pooled from 29 clinical trials that involved more than 18,000 patients. The results showed an excess number of serious cardiovascular adverse events, including angina, myocardial infarction, and stroke, in those taking tegaserod compared with placebo. In each study, patients were assigned at random to either tegaserod or placebo. Tegaserod was taken by 11,614 patients, and placebo was taken by 7,031 patients. The average age of patients in these studies was 43 years, and most patients (ie, 88%) were women. Serious and life-threatening cardiovascular adverse effects occurred in 13 patients (0.1%) treated with tegaserod; among these, 4 patients had a heart attack (1 died), 6 had unstable angina, and 3 had a stroke. Among the patients taking placebo, only 1 (0.01%) had symptoms suggesting the beginning of a stroke that went away without complication.
Loperamide was also found to be useful for women with painless diarrhea. It is now available on the US market. Fedotozine (investigational in the United States) is a kappa-opioid agonist that decreases intestinal hypersensitivity and may help decrease bloating pain. Substance P antagonists are currently being evaluated for the treatment of IBS. Patient support groups can also be useful.

Approximately 60% of patients with chronic pelvic pain may have IBS as a primary or coexistent diagnosis. The Rome criteria for diagnosis should be used in routine clinical practice. Early diagnosis allows the formulation of a management plan that includes counseling and nonpharmacologic interventions, which play important roles in alleviating patient symptoms.

Myofascial pain

Myofascial etiologies occur in 15% of patients with chronic pelvic pain. Trigger points are hyperirritable spots usually within a taut band of skeletal muscle or in muscle fascia. These are painful upon compression and can give rise to characteristic referred pain, tenderness, and autonomic phenomena. Women may experience pain from trigger points (areas overlying muscles that induce spasm and pain) in the myofascial layers of the pelvic sidewall or pelvic floor. The obturator internus and levator ani are common sites and should be palpated. A recent study found levator pain in 87% of women with diagnosed Interstitial cystitis (IC).23 Coexisting symptoms, such as frequent headaches, nonrestorative sleep, diffuse tender points, and fatigue, may be suggestive of systemic disorders such as fibromyalgia.

Treatment for trigger points usually involves hyperstimulation analgesia (eg, stretching, cold spray), local injection of anesthetic agents, TENS, and acupuncture. All of these treatments act as counterirritants that alter the central gate or threshold control and result in the prolonged response. The action of an injected local anesthetic has the effect of blocking the central response. A recent small study of 18 women found improvement in 72% with trigger point injections combining anesthetic agents and triamcinolone. A randomized placebo controlled trial from Australia found significant improvements in non-menstrual pelvic pain and pelvic floor spasms in women treated with Botulinum toxin type A.

Myofascial pain may manifest as focal lower abdominal pain due to entrapment of the genitofemoral or ilioinguinal nerves, which is a sequela of Pfannenstiel incisions. A bupivacaine nerve block is both a diagnostic and therapeutic measure. Cryoneurolysis or surgical removal of the involved nerve should be reserved for recalcitrant cases. Manual therapy of pelvic floor myofascial trigger points is also reported to improve pain in women with IC and in women with frequency-urgency syndrome.

Interstitial cystitis

Considerable overlap exists in symptomatology in patients with IC and IBS. Although some authorities believe that the National Institute of Diabetes and Digestive and Kidney Diseases criteria are too rigid, the criteria still serve as a useful clinical guide for understanding the complex nature of the problem.

Required findings

•   Hunner ulcer or diffuse glomerulations (ie, small bleeding points on the bladder surface seen after hydrodistension of the bladder)
•   Pain associated with the bladder or urinary urgency

Automatic exclusions

 
• Age younger than 18 years  
• Duration of symptoms less than 9 months  
• Urinary frequency fewer than 8 times per day  
• Absence of nocturia  
• Benign or malignant tumors  
• Radiation cystitis  
• Vaginitis  
• Cyclophosphamide cystitis  
• Urethral diverticulum  
• Genital cancer  
• Active herpes infection  
• Bladder or lower ureteric calculi  
• Involuntary bladder contractions  
• Bladder capacity less than 350 mL while awake  
• Symptoms relieved by antibiotics, urinary antiseptics, analgesics, anticholinergics, or muscle relaxants

A recent study found evidence of IC on cystoscopy findings in 38% of patients who underwent laparoscopy for chronic pelvic pain. In a longitudinal study of a cohort of IC patients, the most common sites of pain were lower abdominal (80%), urethral (74%), and lower back (65%).

Two different etiologic mechanisms have been suggested for IC. The classic or ulcerative variant is inflammatory in origin, and the nonulcer variant is neuropathic in origin. This has implications for choice of therapy. An evidence-based therapeutic algorithm for treatment does not exist.

Treatment options
Hydroxyzine is a histamine receptor antagonist with effects on the central and peripheral nervous systems. Hydroxyzine is suggested to have a good clinical effect in patients with IC. The dose is 25-50 mg bid for 14 days.

Amitriptyline is a tricyclic antidepressant that also blocks the H1 histamine receptor. Amitriptyline acts via blockade of acetylcholine receptors, including inhibition of reuptake of released serotonin and norepinephrine. It also has a sedating action via the H1 receptors. A recent placebo-controlled, randomized trial showed significant improvement in patients with IC who were treated with amitriptyline.

Corticosteroids are not widely used because of adverse effects such as fluid retention and osteoporosis. However, a recent study reported improved pain control and overall satisfaction with oral prednisone in a cohort of women with severe refractory IC.

Pentosan polysulfate sodium (PPS) (Elmiron) is claimed to restore the depletion in the glycosaminoglycan (GAG) layer. A double-blind placebo-controlled trial revealed subjective improvements in pain, urgency, frequency, and nocturia. Patients also demonstrated objective improvement in average voided volume. However, no objective demonstration of improvement was noted in urinary frequency. Another study found that the classic subtype of IC responds better than the nonulcer form. In a placebo-controlled trial, one quarter of the patients reported more than 25% improvement. A good response is expected after 4-12 months of treatment, and 50% of patients demonstrate improvement in this time. The dose is 150-200 mg bid between meals. A later study evaluating PPS and hydroxyzine failed to show improvement in most women. Chondroitin sulfate is another drug that replenishes the GAG layer. The dose is 50 mL twice a week, then decreasing to once weekly for 4 weeks. Remission is maintained with monthly instillations.

Intravesical instillation therapy can be performed using agents that are cytoprotective or cytodestructive. Cytoprotective agents include heparin, which may be given in a dose of 20,000 IU in 10 mL of sterile water. Some authors have used methylprednisolone in combination with heparin. A combination of heparin with alkalinized lidocaine was shown to provide better symptom relief than heparin alone.

Cytodestructive agents include dimethyl sulfoxide (DMSO), silver nitrate, and bacille Calmette-Gue’rin (BCG) vaccine. DMSO is a scavenger for intracellular hydroxy free radicals. It is an anti-inflammatory agent and a local anesthetic. It is instilled twice as 50 mL of 50% solution. It may be given with a cocktail of gentamicin, lidocaine, sodium bicarbonate, and heparin. DMSO provides relief in about two thirds of cases, and it increases bladder compliance and inhibits detrusor contractions. BCG is thought to modulate immune responses. It is instilled as 12.5 mg (50 mL) weekly for 4-6 weeks. A recent placebo-controlled trial failed to show significant benefit with BCG.

Capsaicin is another drug that has been successful in patients with IC. Capsaicin is a selective neurotoxin for small myelinated class C afferent neurons. It reflexly inhibits bladder contractions, decreases their amplitude, and increases the residual volume. Patients with urgency and frequency due to idiopathic diabetes insipidus or sensory urgency have not responded as well to capsaicin. Also, 40 mL of 2% lidocaine is given to effect anesthesia from the initial excitation. The dose of capsaicin is 50 mL instilled over a 4-week period. Approximately 44% patients were content with this treatment, and an additional 36% had a decrease in the frequency of urge incontinence. Capsaicin requires reinstillation after 6 months.

Resiniferatoxin is an agent that works on a similar principle. A recent study showed it to be a promising agent for the treatment of IC.

Cystectomy and ileal conduit was the most frequently used major surgical procedure. A review of prescribed treatments in the IC database revealed that cystoscopy with hydrodistension is the most popular treatment. Sacral neuromodulation, hyperbaric oxygen, botulinum toxin (BTX-A), and cyclosporine A are among the newer modalities in the treatment of IC and have been tried with some success. Long-term results are needed before these should be recommended as primary measures.

Urethral syndrome
Patients with urethral syndrome present with classic symptoms of urinary tract infection, but urinary culture results are negative for infection. Symptoms include frequency, urgency, and pressure in the absence of nocturia. Physical examination reveals a tender ropelike urethra. The clinical course is marked by remissions and exacerbations. Causes include chlamydia, mycoplasma, herpes simplex, urethral trauma, atrophy, stenosis, and functional obstruction. Female prostatitis is believed to be due to inflammation of the paraurethral glands and is believed to be a frequent cause of urethral syndrome. Clinical examination reveals localization of tenderness to these glands. Treatment of urethral syndrome should be tailored to the individual cause. Patients with sterile pyuria respond to a 2- to 3-week course of doxycycline or erythromycin. All postmenopausal women should also receive a trial of local estrogen therapy. Urethral dilatation and biofeedback have been used for resistant cases.

Posthysterectomy syndrome
Posthysterectomy syndrome is pain due to a low-grade cuff cellulitis, seroma or hematoma of the cuff, or neuralgia related to transection of the nerve tissue. Resection of a portion of the vaginal cuff occasionally helps relieve the pain.

Hysterectomy for chronic pelvic pain
Long-term studies have shown that success with hysterectomy is disappointing when the only indication is pain (Garcia, 1977). If the pain has persisted for more than 6 months, has not responded to analgesics, and is causing significant distress and impairment, then hysterectomy may be considered an option after counseling the patient that the pain may persist after surgery.

Idiopathic pain
Newer treatment modalities like percutaneous tibial nerve stimulation have shown initial promise. Because of their noninvasive nature, they are likely to be tried in women with unexplained pelvic pain.

Author: Dharmesh Kapoor, MD, MBBS, MRCOG, Subspecialty Fellow, Department of Gynecology, Derriford Hospital

Coauthor(s): Gamal Mostafa Ghoniem, MD, FACS, Fellowship Program Director, Clinical Professor of Surgery, Head, Section of Voiding Dysfunction, Female Urology and Reconstruction, Cleveland Clinic Florida; Willy Davila, MD, Head, Section of Urogynecology and Reconstructive Pelvic Surgery, Chairman, Department of Gynecology, Cleveland Clinic Florida

Editors: Jordan G Pritzker, MD, Assistant Professor of Obstetrics, Gynecology, and Women’s Health, Women’s Comprehensive Health Center, Albert Einstein College of Medicine; Physician-In-Charge, Dept of Obstetrics and Gynecology, Long Island Jewish Medical Center; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Frederick B Gaupp, MD, Consulting Staff, Department of Family Practice, Assumption Community Hospital; Michel E Rivlin, MD, Associate Professor, Coordinator, Quality Assurance/Quality Improvement, Department of Obstetrics and Gynecology, University of Mississippi School of Medicine