Update on Treatment for Chronic Pain

Selection from:
Highlights of the American Academy of Pain Management 19th Annual Clinical Meeting

An Update on Chronic Pain Treatments CME/CE
Andrew N. Wilner, MD, FAAN, FACP

At the 2008 American Academy of Pain Management (AAPM) meeting in Nashville, Tennessee, experts addressed 3 problematic areas of chronic pain: chronic pelvic pain in women, headache, and fibromyalgia.

In order to treat the common problem of chronic pelvic pain in women, clinicians must focus on identifying one of the multiple causes, as many women will respond to therapy. When no cause is found, empiric treatment for unseen endometriosis may be successful.

For patients with chronic headache, the differential diagnosis is wide but severe underlying causes are rare, with most patients suffering from migraine, chronic daily headache, or cluster headache. Because of comorbidities such as bipolar and personality disorder, variability of response to medications, and other factors, algorithms are of limited usefulness and treatment must be individualized.

Fibromyalgia is a disease of multifactorial origin that is still not accepted as a "real disease" by many clinicians but can be diagnosed by specific criteria from the American College of Rheumatology (ACR). The identification and treatment of comorbidities may be even more important in fibromyalgia than in patients with migraine. In all patients with chronic pain, providers must be aware of the potential for addiction in their patients and develop safeguards for its prevention.

Chronic Pelvic Pain
Ayman Al-Hendy, MD, PhD, Director of the Center for Women's Health Research, Meharry Medical College, Nashville, Tennessee, explained that identifying and treating chronic pelvic pain represents a challenge for women's health and primary care practitioners. Up to 15% of women have chronic pelvic pain, but 75% do not consult a healthcare provider and only 10% consult a gynecologist. Chronic pelvic pain may result from a wide spectrum of disorders, including gastrointestinal, gynecologic, musculoskeletal, psychiatric, rheumatologic, and urologic.
In a laparoscopy study of 1318 women with chronic pelvic pain, the most common gynecologic cause for chronic pelvic pain was endometriosis (28%), followed by adhesions (25%) and chronic pelvic infection (6%). Less common causes included ovarian cysts, leiomyomas, pelvic varicosities, and "other." No pathology was identified in 39%, but Dr. Al-Hendy suggested that some of these patients may have had undetected endometriosis.

"Pelvic pain with a negative work-up is usually due to endometriosis when you exclude other causes of pain," advised Dr. Al-Hendy.

Evaluation of chronic pelvic pain begins with a detailed history and physical examination and may require laboratory work, imaging studies and procedures such as laparoscopy. Dr. Al-Hendy asks patients to complete a symptom questionnaire in the waiting room prior to the office examination. For successful treatment of patients with nongynecologic causes of chronic pelvic pain, such as fibromyalgia, irritable bowel syndrome, or urethral syndrome, a multidisciplinary pain clinic may be necessary.

On laparoscopy, endometriosis is characterized by a wide variety of lesions, including vesicles, polyps, "windows," diverticulae, adhesions, vascular "red" lesions, and fibrotic "white" lesions. Lesions may also be black, yellow, or clear. The gold standard for the diagnosis is histopathologic evidence of endometrial glands and stroma. Dr. Al-Hendy added that the severity of endometrial disease seen on laparoscopy doesn't correlate well with symptom severity. Further, lesions may remain hidden even from properly performed laparoscopy.

Laparoscopic laser treatment yields significant improvement in 100% of patients with severe endometriosis, 69% of patients with mild disease, and 38% of patients with minimal disease. Dr. Al-Hendy suggested that patients with minimal disease may have lesions hidden from the laparoscope, accounting for the poor treatment response.

The addition of hormonal treatment, a gonadotropin-releasing hormone (GnRH) agonist that induces a "chemical menopause," improves the results of surgical treatment. Even a GnRH agonist without surgery controls symptoms in almost 90% of patients for 1 year, with recurrence of pain symptoms in 50% of patients at 4 years. Dr. Al-Hendy recommended that patients keep a diary of their pain symptoms, which are important to separate from the menopausal symptoms that may result from GnRH therapy, such as headaches, night sweats, and hot flashes.

If there are no visible lesions of endometriosis and the pain does not respond to a GnRH agonist, the cause is probably not endometriosis, concluded Dr. Al-Hendy.

Management of Headache
Lawrence Robbins, MD, Assistant Professor of Neurology at Rush Medical College, Chicago, Illinois, and Director of the Robbins Headache Clinic, Northbrook, Illinois, was the recipient of this year's AAPM Clinical Pain Management Award. In his presentation he reviewed the treatment of chronic headache, with an emphasis on migraine. Other causes of chronic headache include chronic daily headache, cluster headache, and, more rarely, intracranial pathology.
According to Dr. Robbins, migraine affects 28 million people in the United States and is common in all age groups. In addition to head pain, symptoms characteristic of migraine headaches include nausea, photophobia, and relation to the menstrual cycle.

Dr. Robbins explained, "Migraine is like having asthma or diabetes. It's a physical problem."
Patients should be educated about possible migraine triggers. These include relation to the menstrual cycle, undersleeping, stress and daily hassles, weather changes, missing meals, bright lights, and specific foods and drinks. These triggers can be cumulative, resulting in a headache. For example, a weather change occurring on the first day of the menstrual period may trigger a migraine.

Dr. Robbins advised that people with migraine pay attention to their caffeine ingestion. Small amounts of caffeine can help headaches, and 150-200 mg, the amount in a single cup of coffee, is usually enough. However, caffeine tolerance can develop. Some people who miss their routine cups of coffee will develop headaches or depression due to caffeine withdrawal.

Medications are most effective when used early in the headache. There are many choices of triptans, which may be combined with nonsteroidal anti-inflammatory drugs (NSAIDs). Triptans are more effective when used early, before allodynia and sensitization begin. Nontriptan abortive medications include acetaminophen, aspirin, NSAIDs, caffeine, and metoclopramide, as well as dichloralphenazone alone and in combination. Dihydroergotamine (DHE) injections and dihydroergotamine and caffeine nasal spray are also options. Antiemetics include ondansetron and promethazine. Other pain medications include opioids, butalbital, and hydrocodone. Dr. Robbins uses steroids, injectable opioids, butorphanol nasal spray, and fentanyl when the usual abortives do not work. For some patients with intractable headaches, monoamine oxidase inhibitors (MAOIs), stimulants, occipital stimulators, patent foramen ovale surgery, occipital nerve blocks, and cervical injections may be helpful. Dr. Robbins objected to the use of algorithms for the treatment of headache.

"Comorbidities shape how we treat headache patients; anxiety, depression, bipolar spectrum and personality disorders, attention-deficit/hyperactivity disorder, addictions, and insomnia will all influence how we treat the headache," observed Dr. Robbins. "Medical comorbidities that affect the gastrointestinal system, irritable bowel syndrome, constipation, and diarrhea will also influence treatment choice," he added.
"For example, amitriptyline can cause weight gain, constipation, and fatigue, so we wouldn't use it in patients predisposed to these symptoms."

In addition to medical therapies, psychotherapy, biofeedback, exercise, yoga, massage, acupuncture, and other treatments may be useful. "Acceptance is very important, not resignation," advised Dr. Robbins. "However, the patient may have acceptance, but their spouse or family may not, which increases the anxiety and stress of the patient. In addition, active coping is very important compared to passive coping. We want to promote self-efficacy."
Dr. Robbins concluded, "We are not treating headaches, we are treating people and trying to enhance quality of life."

Management of Fibromyalgia
Philip Mease, MD, Chief, Division of Clinical Research, Swedish Hospital Medical Center, Seattle, Washington, described fibromyalgia as a condition characterized by heightened pain sensitivity, fatigue, sleep disturbance, and other symptoms due to dysregulation of neurophysiologic function. Fibromyalgia is not simply a condition that occurs in the developed world; it has a prevalence worldwide ranging from 0.7% (Denmark) to 10.5% (Norway). In the United States, the prevalence of fibromyalgia is 2%.

Fibromyalgia may be diagnosed by applying ACR criteria, which include a history of chronic widespread pain for at least 3 months and identification of at least 11 out of 18 tender points. The ACR diagnostic criteria are 88.4% sensitive and 81.1% specific. Fibromyalgia appears to have a multifactorial pathophysiology, which includes a strong familial predisposition, central pain amplification, psychiatric comorbid conditions, and other factors, such as immune dysregulation and the role of neurohormones such as dopamine, and growth hormone. Magnetic resonance imaging studies have provided objective evidence to show that patients with fibromyalgia have a lower threshold for pain sensitivity.

Multiple comorbid symptoms and syndromes may accompany fibromyalgia, including tension/migraine headache, affective disorders, temporomandibular joint disorder, idiopathic low back pain, irritable bowel syndrome, nondermatomal paresthesias, fatigue, memory and cognitive difficulties, and others. Tension headache is one of the most common comorbidities, occurring in over 70% of women and 50% of men with fibromyalgia.

After confirming a diagnosis, Dr. Mease recommended the identification of important symptom domains, their severity, and level of patient function. The only diagnostic instrument that has been validated for measure of function and quality of life in fibromyalgia is the Fibromyalgia Impact Questionnaire (FIQ). Patients should be evaluated for comorbid medical and psychiatric disorders, psychosocial stressors, level of fitness, and barriers to treatment. Education should be provided about fibromyalgia and treatment options should be reviewed.

Despite different modes of action, a variety of neuromodulatory agents may improve the symptoms of fibromyalgia patients. These include antidepressants, analgesics, anticonvulsants, muscle relaxants, and sedative hypnotic drugs. Only 2 drugs are FDA-approved for the specific treatment of fibromyalgia: pregabalin (Lyrica®) and duloxetine hydrochloride (Cymbalta®). However, many other medications are used off-label for the treatment of fibromyalgia.
Two pivotal phase 3 trials of the investigational drug milnacipran have been completed recently and showed favorable results for the treatment of fibromyalgia. Statistically significant durable pain relief as well as multidimensional symptom improvement lasted at least 1 year. The main adverse event was nausea (36.7%), with other adverse effects similar to those associated with duloxetine. Milnacipran has been approved in Europe and Asia for the treatment of depression.
Nonpharmacologic therapy for fibromyalgia includes aerobic exercise, cognitive-behavioral therapy, patient education, strength training, acupuncture, biofeedback, balneotherapy, and hypnotherapy. Both the patient's pain and comorbid conditions should be treated. Referral to a specialist may be necessary for complex cases.

Conclusions
The treatment of chronic pelvic pain, migraine, and fibromyalgia requires a directed history, physical examination, and laboratory evaluations to rule out other diagnoses and appreciation of multiple comorbidities that may influence the expression of symptoms and guide treatment choice. Multiple treatment modalities are available, which must be individualized for each patient.
This activity is supported by an educational grant from PriCara, Division of Ortho-McNeil-Janssen Pharmaceuticals Inc., administered by Ortho-McNeil Janssen Scientific Affairs, LLC.