Thursday, March 13, 2014

Pain Medicine News - Fibromyalgia Now Widely Recognized as Requiring Multimodal Approach

Israeli fibromyalgia guidelines published online in November 2013 and Canadian guidelines published in May 2013 follow in the solid footsteps of the 2010 American College of Rheumatology preliminary diagnostic criteria for fibromyalgia. The Canadian and Israeli documents eschew an extensive physical examination and a tender-point count, focus on the importance of nonpharmacologic treatments and recognize fibromyalgia as neither a distinct rheumatic nor mental disorder. German guidelines cut from similar cloth were published in 2008.

"All three guidelines focus on a multimodal approach; and we emphasize the primacy of physical activity and self-management strategies that may be augmented by interventions such as cognitive-behavioral therapy. Mary-Ann Fitzcharles, MD, lead author of the Canadian guidelines (Pain Res Manag 2013;18:119-126), said after discussing the three guidelines at the American College of Rheumatology's 2013 annual meeting, "Medications do play a role in patient care, but with the acknowledgment that responses are generally modest at best."

Jacob Ablin, MD, lead author of the Israeli guidelines (2013; 152:L742-L747;​Ima/​FormStorage/​Type7/​clinical_68_fibrom.pdf) and director of the Fibromyalgia Clinic at the Tel-Aviv Sourasky Medical Center, told meeting attendees the Israeli and German guidelines also recommend against the use of nonsteroidal anti-inflammatory drugs, systemic steroids, benzodiazepines and thyroid hormone. Additionally, all three guidelines caution about the side effects of medications, which may mimic fibromyalgia symptoms.

"Fibromyalgia is not rheumatoid arthritis," emphasized Dr. Ablin. "Until we have true DMARDs [disease-modifying antirheumatic drugs] for fibromyalgia, pharmacologic treatment is a useful adjunct, not an imperative."

Star Role for Primary Care

Another expert in the field who was not involved with development of any of these guidelines made another important point: The Canadian guidelines put primary care doctors on the front lines. The German guidelines (Ger Med Sci 2008;9:Doc14) do the same.

"I'm familiar with the Canadian guidelines and am impressed that they turn it back to the family doc and provide tools for them to do the diagnosis and treatment in most cases," said Anthony Russell, MD, professor of medicine, University of Alberta, Edmonton, Canada, in an email toPain Medicine News.

The guidelines all focus on fibromyalgia as a cluster of symptoms with pain as the primary complaint, but with other manifestations that significantly contribute to patient suffering such as sleep disorder, fatigue and mood disorder. They all give grade A recommendations to aerobic exercise, multicomponent therapy and cognitive-behavioral therapy. Amitriptyline, started at a low dose, is given a grade A by the Canadian and Israeli guidelines, and a grade C recommendation by the Germans. The serotonin-norepinephrine reuptake inhibitors duloxetine and milnacipran (Savella, Forest Laboratories) are given a grade A recommendation by the Canadians and Israelis and grades B/C by the Germans (B for patients with comorbid depressive or generalized anxiety disorder and C for people without either of these comorbidities), whereas the anticonvulsants gabapentin and pregabalin (Lyrica, Pfizer) receive grades A and C, respectively. The evidence for other therapies such as balneotherapy (spa therapy), selective serotonin reuptake inhibitors and tramadol is more equivocal.

The German guidelines give much more credence to complementary and alternative medicine than do the other two: They give grade A recommendations to meditative movement therapies such as yoga and tai chi, and relaxation training combined with exercise, and grade C recommendations to acupuncture, biofeedback and hypnosis or guided imagery. The Israelis give a grade C recommendation for tai chi. The Canadian guidelines categorize yoga and tai chi as exercise activities.

The German and Israeli guidelines also call for stepwise treatment based on disease severity. For example, they recommend that individuals with mild or moderate fibromyalgia continue aerobic exercise, with increases as patients regain strength and overall health.

"Patients and physicians alike need to know that fibromyalgia is not a disabling condition for the majority of patients and that improvement is achievable," said Dr. Fitzcharles, associate professor of medicine, Division of Rheumatology, McGill University, Montreal, Quebec. "Contrary to many people's perception that fibromyalgia always has an adverse outcome, the objective of treatment and patient goals should to be to remain in the normal swing of life as best as possible."

Wednesday, March 12, 2014

FDA Approves First Device to Prevent Migraine

The US Food and Drug Administration (FDA) today allowed marketing of the first device for the preventive treatment of migraine headaches (Cefaly, STX-Med).

It is also the first transcutaneous electrical nerve stimulation (TENS) device specifically authorized for use before the onset of pain, the FDA noted in a statement released today.

"Cefaly provides an alternative to medication for migraine prevention," Christy Foreman, director of the Office of Device Evaluation at the FDA's Center for Devices and Radiological Health, said in the statement. "This may help patients who cannot tolerate current migraine medications for preventing migraines or treating attacks."

The device, which resembles a plastic headband worn across the forehead and over the ears, stimulates the trigeminal nerve using a self-adhesive electrode in the center of the forehead. "The user may feel a tingling or massaging sensation where the electrode is applied," the FDA notes. "Cefaly is indicated for patients 18 years of age and older and should only be used once per day for 20 minutes."

The FDA reviewed the data for Cefaly through the de novo premarket review pathway, a regulatory pathway for generally low- to moderate-risk medical devices that are not substantially equivalent to an already legally marketed device.

Two Studies

The approval was based on data from a clinical study conducted in Belgium involving 67 individuals who experienced more than 2 migraine headache attacks a month and who had not taken any medication to prevent migraines for 3 months before using the device, as well as a patient satisfaction study of 2313 device users in France and Belgium.

The 67-person study, published in Neurology, showed that those who used the device experienced significantly fewer days with migraines per month and took less migraine attack medication than those who used a placebo device. The device did not completely prevent migraines and did not reduce the intensity of migraines that did occur, the FDA notes.

"The patient satisfaction study showed that a little more than 53% of patients were satisfied with Cefaly treatment and willing to buy the device for continued use," the statement adds. "The most commonly reported complaints were dislike of the feeling and not wanting to continue using the device, sleepiness during the treatment session, and headache after the treatment session."

No serious adverse events occurred during either study, the agency notes.

The device is already available in Europe, as well as several South American and Middle Eastern countries and Canada.

Monday, March 03, 2014

Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION)

The mission of the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership with the United States Food and Drug Administration (FDA) is to identify, prioritize, sponsor, coordinate, and promote innovative activities — with a special interest in optimizing clinical trials — that will expedite the discovery and development of improved analgesic, anesthetic, and addiction treatments for the benefit of the public health.
ACTTION is a multi-year, multi-phase initiative that is closely aligned with the FDA's Critical Path Initiative. This public-private partnership has been designed to streamline the discovery and development process for new analgesic, anesthetic, and addiction medications and to more generally accelerate the development of treatments with improved efficacy and safety.
The key objectives of ACTTION involve initiating and supporting strategic collaborations among a broad spectrum of stakeholders — including, but not limited to, academia, the FDA and other government agencies, industry, professional organizations, patient advocacy groups, foundations, and philanthropic organizations — with the goals of sharing data and innovative thinking about the development of novel therapeutics. These strategic collaborations involve a wide range of research projects and other activities, for example, scientific workshops, consensus meetings, and in-depth analyses of clinical trial data to determine the effects of research methods on study assay sensitivity and efficiency.

Saturday, March 01, 2014

Sensitization and Catastrophizing: Introspection Confirmed Experimentally | Pain Research Forum

I had a strange experience recently. My own reaction to it seemed interesting enough to warrant closer examination, and that, in turn, led to a useful insight. Eighteenth century philosophers recognized the limitations of such introspection, but it continues to be a source of psychological insight and hypotheses. I have sometimes learned to understand patients' experiences better by considering my own. In this case, experimental confirmation of what I learned quickly followed.

Last fall I acquired a walking treadmill. I raised my desk and placed the treadmill under it, allowing me to walk while I work. I quickly learned to walk, think, and dictate text to the computer with little cross-task interference. Walking at 2-3 km/h, I could comfortably cover 5 to 10 km a day, get some exercise, burn a few hundred calories and do some writing. This happy outcome lasted for about six weeks.

Then this arrangement fell apart for what seemed like a ridiculous reason. When I walked on the treadmill for progressively shorter periods of time, a powerful aversive sensation would build up in the soles of my feet. With every step, it felt as if I had one or more pieces of small, sharp gravel in my shoes. I kept stopping to inspect my shoes and socks and never found anything that could account for the sensation. Yes, perhaps there were tiny irregularities in the insoles of my shoes or inside my socks, but there was nothing like the sharp gravel my soles were reporting to my brain. I would rate the pain intensity at 3/10 and the unpleasantness at 8/10. The pain would stop a few minutes after I stopped walking on the treadmill, but would return quicker and stronger each time I resumed.

Interestingly, the problem never occurred during ordinary walking. I could easily walk 5 km outdoors without experiencing these aversive sensations in the soles of my feet.

At this point, two months after installing the desk treadmill, some serious catastrophizing set in. I told myself, "I wasted $1200. I'll never be able to use this treadmill. I'll have to go back to sitting at a desk. So much for my fitness plan," and similar discouraged thoughts. When I did attempt to walk on the treadmill while working, I could not concentrate on the work at all: my mind was almost fully occupied with the sensation in my feet and with those catastrophizing thoughts. Realizing this led to a vicious cycle of increased catastrophizing: "What an idiot – I ought to be able to focus on my work!"

After several weeks of this struggle, I finally remembered what should have been obvious to me as a pain researcher and as a person who has observed quantitative sensory testing in both clinical and research settings. I was experiencing neural sensitization to the prolonged and regular repetition of identical physical stimuli produced by walking on the treadmill.

In what has been called the "Chinese water torture" (which is probably not Chinese in origin and was described in Europe in the 16th century), a small drop of water falls at regular intervals on the restrained victim's forehead, becoming agonizing after a while. This is a classic example of sensitization. I realized that putting my feet down in a mechanically regular pattern had the same effect. The feelings in my feet corresponded to the classic phenomena of sensitization including allodynia (interpreting a normal touch as painful) and windup (progressively stronger response to the same stimulus).

With this insight, the cure was obvious: I had to vary the stimulus. This turned out to be easy. When the sharp gravel sensation starts, I kick off my shoes and continue walking in my socks or bare feet; if I am already barefoot when the sensitization begins, I put my socks and shoes back on. I vary the speed setting on the treadmill so that my footfalls occur at different intervals. I vary the way I walk, placing weight on different parts of my feet. Sometimes I just stand for a while. These actions vary the frequency, location, intensity and quality of the stimuli on my feet, thus reducing the sensitization.

Because of these minor changes I can continue my work with little interference. The sensitization still occurs (pain 1/10, unpleasantness 3/10), but it doesn't bother me because I know what to do. In other words, the sensitization is not amplified by catastrophizing and helplessness.

This experience helps me to understand patients whose pain is worsened by sensitization. I don't think this neurophysiological phenomenon is widely understood outside the circles of pain specialists. The combination of sensitization and catastrophizing is dramatically distressing and disabling. Changing either can influence the other.

Coincidentally, the day after I wrote the above, an article by Salomons and colleagues was published online in Pain, providing experimental confirmation of what I learned through direct experience. In this study, repeated thermal stimuli were applied to participants' forearms, producing hyperalgesia. Half the participants were given a cognitive intervention to reduce their stress response to the painful stimuli by identifying negative cognitions and reappraising the situation. In comparison with a control condition, the cognitive intervention led to reduced unpleasantness ratings. The authors conclude, "Reduction in secondary hyperalgesia was associated with reduced pain catastrophizing, suggesting that changes in central sensitization are related to changes in pain-related cognitions. Thus, we demonstrate that central sensitization can be modified volitionally by altering pain-related thoughts."

The take-home message: let's watch out for sensitization and catastrophizing and their mutually reinforcing interaction, in our patients and in ourselves.

Have you experienced sensitization and hyperalgesia in your own life? What did you do, physically and psychologically, to deal with it? Did you learn anything from that experience that informs your research or clinical practice? What other research bears on this relationship between sensitization and catastrophizing?