Gynecologic Pain

INTRODUCTION

¡@

The uterus, cervix, and adnexa share the same visceral innervation as the lower ileum, sigmoid colon, and rectum. Signals travels via the sympathetic nerves to spinal cord segments T10 through L1. It often is difficult to distinguish between pain of gynecologic and gastrointestinal origin due to this shared pathway (Jones, 1996).

ACUTE PELVIC PAIN

¡@

Acute pain due to ischemia or injury to a viscus is accompanied by autonomic reflex responses such as nausea, vomiting, restlessness, and sweating. The following is a discussion of some of the important gynecologic causes of acute abdominal pain.

Culdocentesis is a very useful diagnostic aid in differentiating the cause of acute gynecologic pain. In the absence of a positive pregnancy test, fresh blood suggests a corpus luteum hemorrhage, old blood suggests a ruptured endometrioma (chocolate cyst), purulent fluid suggests acute PID, and sebaceous fluid indicates a dermoid cyst.

¡@

Ectopic pregnancy

An unruptured ectopic pregnancy produces localized pain due to dilatation of the fallopian tube. Once ruptured, the pain tends to be generalized due to peritoneal irritation. Symptoms of rectal urgency due to a mass in the pouch of Douglas also may be present. Syncope, dizziness, and orthostatic changes in blood pressure are sensitive signs of hypovolemia in these patients.

Abdominal examination findings include tenderness and guarding in the lower quadrants. Once hemoperitoneum has occurred, distension, rebound tenderness, and sluggish bowel sounds may develop.

Pelvic exam may reveal cervical motion tenderness that is exaggerated on the side of the tubal ectopic.

Initially, a sensitive serum or urine pregnancy test should be performed. A positive pregnancy test should be followed by culdocentesis to detect any unclotted blood. A hematocrit less than 16% (in the peritoneal blood) rules out hemoperitoneum. Transvaginal ultrasound should be performed. If an intrauterine gestational sac with a fetal pole is identified, the chances of a coexisting ectopic pregnancy are remote. Such a heterotopic gestation should be considered in patients taking ovulation-inducing drugs. Serial serum beta-hCG estimations often are helpful in making the diagnosis. In early intrauterine gestations, the doubling time for hCG usually is 48 hours. Only 15% of cases are exceptions to this rule.

Laparoscopy should be attempted if the patient is hemodynamically unstable, there remains a high index of suspicion, or the patient complains of increasing pain despite adequate analgesia.

Treatment options for an unruptured ectopic pregnancy include salpingostomy and salpingectomy. This may be performed laparoscopically or by open procedure. Methotrexate, a folic acid antagonist, also is used for the treatment of unruptured ectopic pregnancy. A ruptured ectopic pregnancy requires a laparotomy with removal of blood clots.

¡@

Adnexal masses

Corpus luteum hematoma

This condition develops in the luteal phase of the menstrual cycle. Slow leakage produces minimal pain. Frank hemorrhage can lead to hemoperitoneum and hypovolemic shock. Generalized abdominal pain and syncope are features of such a presentation. Treatment includes laparoscopy or laparotomy, evacuation of clots, and control of ovarian bleeding.

Ruptured ovarian cyst

The most common causes are dermoid cyst, cystadenoma, and endometrioma. Since the amount of blood loss is minimal, hypovolemia does not supervene. Peritoneal irritation due to leakage of cyst fluid can lead to significant tenderness, rebound tenderness, abdominal distension, and hypoperistalsis. Treatment involves cyst removal.

Ovarian torsion

Changes in ovarian axial morphology, which typically are secondary to ovarian cysts (most commonly dermoids), can undergo torsion around the pedicle. Frequently, torsion resolves spontaneously, and the only presenting symptom is lower abdominal pain. Persistent torsion progresses to occlusion of the venous drainage of the ovary, which leads to congestion, ovarian enlargement, thickening of the ovarian capsule, and subsequent infarction. Pain eventually becomes severe and is accompanied by nausea, vomiting, and restlessness. Infarction also leads to fever and mild leukocytosis.

If the ovary appears viable on laparoscopic examination, the pedicle may be untwisted and the cyst removed. An infarcted ovary needs to be removed.

Acute pelvic inflammatory disease

RECURRENT PELVIC PAIN

¡@

Mittelschmerz

Mittelschmerz is midcycle abdominal pain due to leakage of prostaglandin-containing follicular fluid at the time of ovulation. It is self-limited, and a theoretical concern is treatment of pain with prostaglandin synthetase inhibitors, which could prevent ovulation.

Endometriosis

Pain associated with endometriosis may worsen premenstrually or during menses. Patients experience generalized lower abdominal tenderness, and associated complaints include dysmenorrhea, dyschezia, and dyspareunia. Endometriotic deposits in both the uterosacral ligaments and rectovaginal septum contribute to pain during intercourse. Painful defecation is due to infiltration of the bowel wall by endometriotic deposits. It is important to remember that the pain associated with endometriosis is not correlated with the presence or amount of visible endometriotic tissue. In fact, prevalence of endometriosis is the same in women with and without pain (Kresch, 1984; Cunanan, 1983). Rather, pain is related to the chemical mediators of inflammation and neural infiltration.

Ovulation suppression using different drugs has been tried in order to reduce the pain associated with endometriosis. Overall, no difference appears to exist in the efficacy of danazol, gestrinone, oral contraceptives, depot medroxyprogesterone acetate, and gonadotropin-releasing hormone (GnRH) analogs in placebo-controlled trials. Dydrogesterone, however, was found to be less effective.

In systematic reviews, laparoscopic ablation of endometriotic implants using diathermy or laser remains unproven as a treatment modality for pain or subfertility. One study, however, did find that a combination of ablation and laparoscopic uterine nerve ablation (LUNA) was more effective at relieving pain. During postoperative treatment, GnRH analogs resulted in significantly reduced pain scores in women who received treatment for 6 months.

Laparoscopic cystectomy of an endometrioma was found to be superior to simple drainage for treatment of recurring pain.

GnRH agonists were used for 6 months in patients with documented endometriosis as the only treatment. At 5 years, more than half of patients were symptom-free. The best responses were obtained in patients with mild or moderate disease. Among those with persistent or recurrent pain, there was an increasing correlation with the severity of the endometriosis. (Waller, 1993)

Primary dysmenorrhea

By definition, primary dysmenorrhea is menstrual pain associated with ovulatory cycles in the absence of structural pathology. It usually presents in younger women. Patients experience suprapubic, cramping pain that may radiate to the anterior thigh or sacral region. Pain may be accompanied by autonomic symptoms such as nausea, vomiting, and syncope. The onset of primary dysmenorrhea is a few hours prior to the onset of menses, and pain usually lasts for up to 72 hours. More than 80% of patients have an excellent response to treatment with prostaglandin synthetase inhibitors. Oral contraceptives may be used with equal effectiveness in patients who desire simultaneous fertility control.

Smoking was associated with a higher relative risk of severe dysmenorrhea. In a systematic review, naproxen, ibuprofen, and mefenamic acid were more effective for pain relief compared to placebo. A Cochrane database review of trials evaluating oral contraceptives for treatment of dysmenorrhea currently is underway.

Secondary dysmenorrhea

Secondary dysmenorrhea is cyclic menstrual pain associated with structural pathology. The most common causes are endometriosis, adenomyosis, and presence of an intrauterine device. Pain starts 1-2 weeks prior to the onset of menses and persists for a few days after cessation of flow. Hypertonic uterine activity coupled with an excess of prostaglandins is postulated to be the cause of secondary dysmenorrhea. Patients are somewhat less responsive to nonsteroidal anti-inflammatory drugs (NSAIDs) and combination oral contraceptives than patients with primary dysmenorrhea.

Adenomyosis

CHRONIC PELVIC PAIN

¡@

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 (ACOG, 2001).

Annually, 400,000 laparoscopies are performed on patients with endometriosis and chronic pelvic pain. Negative laparoscopic findings occur in 40% of patients (Howard, 1993).

Important nongynecologic causes that must be considered in the differential diagnosis include irritable bowel syndrome (IBS), interstitial cystitis (IC), and pelvic floor myofascial syndrome. It is important to rule out abdominal wall etiologies that are aggravated by head raising or straight-leg raising while supine.

Dyspareunia as a significant factor

Patients with deep, internal, or thrust dyspareunia often express a feeling that something is being bumped into 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 also may cause dyspareunia and pain at the apex of the vagina.

Adhesions

The density or location of adhesions is not correlated with degree of pain (Rapkin, 1986). 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 (Chan, 1985). In a randomized study, patients with severe adhesions involving the intestinal tract were shown to benefit from adhesiolysis (Peters, 1992). 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 (Bost, 2001).

Chronic PID

Pain is due to infection or adhesions that exacerbate the baseline pain. Infection may be accompanied by fever, leukocytosis, and gonococcal or chlamydial infection. Laparoscopy and peritoneal fluid cultures 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 (TAHBSO), 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 often is fruitless due to the density of adhesions, and a laparotomy is the surgical procedure of choice for tissue removal. It may be challenging to find the ovarian tissue.

¡@

IBS

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 (Thompson, 1999)

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. On examination, a tender sigmoid colon often is palpable. Fiber supplementation 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 (Drossman, 1996).

Low-dose antidepressants such as amitriptyline and selective serotonin reuptake inhibitors (SSRIs) may have an adjunctive role. Alosetron was approved by the United States Food and Drug Administration for constipation-predominant IBS, but it was withdrawn because of several episodes of ischemic colitis. Newer medications being evaluated for IBS include tegaserod, which is a 5-hydroxytryptamine (5-HT₄) receptor partial agonist that helps symptoms of IBS, alleviates constipation, and accelerates intestinal transit. Fedotozine is a kappa-opioid agonist that decreases intestinal hypersensitivity and may help decrease bloating pain. Substance P antagonists currently are being evaluated for the treatment of IBS. Patient support groups also can be very 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 suffering.

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 on 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. 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 (such as stretch and cold spray), local injection of anesthetic agents, transcutaneous electrical stimulation (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 (Slocumb, 1990).

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.

Interstitial cystitis

There is considerable overlap in symptomatology in patients with IC and IBS. Although some authorities think that the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 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 (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 cc while awake
• Symptoms relieved by antibiotics, urinary antiseptics, analgesics, anticholinergics, or muscle relaxants
  ¡@

A recent study found evidence of IC on cystoscopy in 38% of patients who underwent laparoscopy for chronic pelvic pain (Clemons, 2001).

It also has been suggested that IC has 2 different etiologic mechanisms. The classic or ulcerative variant is inflammatory in origin, and the non-ulcer variant is neuropathic in origin. This has implications for choice of therapy. An evidence-based therapeutic algorithm for treatment does not exist (Hanno, 2001).

Treatment options

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

Amitriptyline is a tricyclic antidepressant (TCA) 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.

Corticosteroids are not widely used because of equivocal results and side effects such as fluid retention and osteoporosis.

Sodium pentosan polysulfate (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. There was, however, no objective demonstration of improvement in urinary frequency. Another study found that the classic subtype of IC responds better than the non-ulcer 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. Dose is 150-200 mg bid between meals.

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. Cytodestructive agents include dimethyl sulfoxide (DMSO), silver nitrate, and bacille Calmette-Guin (BCG).

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. Lidocaine has been shown to provide temporary symptom relief and is another option for intravesical treatment. Chondroitin sulfate is another drug that replenishes the GAG layer. Dose is 50 mL twice a week, then decreasing to once weekly for 4 weeks. Remission is maintained at monthly instillations. BCG is thought to modulate immune responses. It has more potential risks and is only experimental at present. It is instilled as 12.5 mg (50 mL) weekly for 4-6 weeks.

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. 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. 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.

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

The most favored oral treatments included amitriptyline, pentosan polysulfate, and NSAIDs. The most favored intravesical treatments were DMSO cocktail, heparin sulfate, and an anesthetic cocktail. Cystectomy and ileal conduit was the most frequently used major surgical procedure. Sodium pentosan polysulfate remains the only oral therapy approved by the United Stated Food and Drug Administration for the treatment of IC. A review of prescribed treatments by the IC database revealed that cystoscopy with hydrodistension was the most popular treatment. Recently, sacral nerve stimulation (Interstim) has been tried with some success. Long-term results should be awaited before recommending this as a primary measure.

¡@

Urethral syndrome

Patients with urethral syndrome present with classic symptoms of urinary tract infection, but urinary culture is negative for infection. Symptoms include frequency, urgency, and pressure in the absence of nocturia. Physical examination reveals a tender ropelike urethra. Clinical course is marked by remissions and exacerbations. Causes include chlamydia, mycoplasma, herpes simplex, urethral trauma, atrophy, stenosis, and functional obstruction. Treatment 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 also should 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 in relieving the pain (Butrick, 1995).

¡@

Treatment modalities for chronic pelvic pain

Laparoscopy

Laparoscopy of endometriotic deposits has been used to treat symptoms associated with endometriosis, although this procedure has not led to symptom resolution in many cases. Recently, there has been interest in a technique called conscious pain mapping that allows patients to identify specific lesions that cause pain. In cases of endometriosis, there was a predictive value with histologically diagnosed endometriosis but not visually diagnosed endometriosis (Howard, 2000).

Laparoscopic uterine nerve ablation

The uterosacral ligaments carry many sensory afferent fibers to the lower parts of the uterus by way of the Lee-Frankenhäuser plexus, which lies in and around the uterosacral ligaments as they insert upon the posterior aspects of the cervix. Laparoscopic uterine nerve ablation (LUNA) has been used for the treatment of pain due to endometriosis and dysmenorrhea; its efficacy was proven for both conditions. Both electrocoagulation and laser diathermy were found to be effective (Lichten, 1987; Ewen, 1994; Damaro, 1994). LUNA was found to be significantly superior to diagnostic laparoscopy at 12 months follow-up. Another trial compared LUNA to laparoscopic presacral neurectomy (LPSN). The latter had superior pain relief at 12 months; however, 94% of patients complained of constipation following LPSN compared to 0% in the LUNA group.

Presacral neurectomy

Presacral neurectomy is an effective treatment for dysmenorrhea, dyspareunia, and pelvic pain. It also has reduced pain in cancer patients. (Biggerstaff, 1994; Perez, 1990; Nezhat, 1992; Garcia, 1977; Plancarte, 1990)

Hysterectomy

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 as an option after counseling the patient that the pain may persist after surgery.

Other treatments

Transcutaneous electrical nerve stimulation (TENS) is reportedly superior to placebo, but it is less effective than ibuprofen for treatment of dysmenorrhea.

VULVAR PAIN

¡@

Vulvovaginitis may be due to allergic reaction (contact vaginitis), infection (bacterial, parasitic, fungal), or hypoestrogenism (atrophic). Symptoms include burning, discomfort, dyspareunia, and abdominal vaginal discharge. It is important to localize the pain in order to arrive at a diagnosis.

Contact vulvitis

The patient usually complains of itching or burning that involves the vulva but not the vagina. Elimination of the suspected agent and topical steroids for 7-10 days usually results in resolution of symptoms.

Atrophic vaginitis

Primary complaints include burning, dyspareunia, and vaginal spotting. The patient also may experience burning during micturition, urinary urgency, and urinary frequency. Topical estrogen cream is the first-line treatment. Incidence of systemic absorption is low with low-dose topical estrogens.

Microbial vaginitis

The usual complaints are accompanied by vaginal discharge. Appropriate treatment results in resolution of symptoms.

Vulvodynia

Essential vulvodynia is a diffuse, unremitting vulval burning that may radiate to the inner thigh, buttocks, and perineum. Associated complaints include urethral and rectal burning or discomfort. This is a condition commonly found in postmenopausal women. Physical examination reveals hyperalgesia in the affected areas. Prevalence is unknown. Pudendal nerve damage or compression is a possible contributory factor. Urinary frequency, urgency, and incontinence may develop as a consequence, and chronic constipation also may develop. Amitriptyline has been used with some success in the treatment of vulvodynia.

Vulvar vestibulitis is a subset of vulvodynia. The obligatory components are severe pain on vestibular touch or attempted vaginal entry, tenderness to pressure localized within the vulvar vestibule, and physical findings limited to vestibular erythema of various degrees. It has been suggested that since both the vestibule of the vulva and the bladder are derived from the urogenital sinus, there is a common etiology to these conditions.

PAIN DUE TO COMPLICATIONS OF GYNECOLOGIC SURGERY

¡@

Thermal bowel injury is a serious complication of surgery. It occurs in 0.5-3.2 per 1000 cases, and symptoms may not develop for days or weeks. Patient presentation includes bilateral lower quadrant pain, tenderness, fever, leukocytosis, and peritonitis. Ileus or free gas under the diaphragm may be noted on a plain abdominal x-ray.

Peritonitis may occur as a consequence of undetected bowel perforations. Other complications include abscess, enterocutaneous fistula, and septic shock.

Thermal injury to the bladder or ureter may present up to 14 days postoperatively with abdominal or flank pain, fever, and peritonitis. An intervenous pyelogram demonstrates extravasation of urine or urinoma. Patients with mechanical obstruction may present in 1 week with a similar clinical picture.

Incisional herniae rarely become incarcerated. Patients present with abdominal pain and signs of bowel obstruction or perforation.

Hysteroscopy commonly leads to uterine perforation, which may involve the bowel. Such a possibility should be kept in mind when evaluating a patient.

Following a vaginal hysterectomy, patients may present with pelvic pain due to vaginal cuff hematoma, cellulitis, or ovarian abscess. Wound compilations such as dehiscence, renal angle pain due to ureteric injury, and retention should be considered.