Arthritis Pain and Beyond: Coverage from the 2011 American College of Rheumatology/Association of Rheumatology Health Professionals Annual Meeting

In addition to offering sessions that covered more traditional topics in pain management, including presentations on the evaluation and treatment of back pain, assessing sleep disturbance in fibromyalgia, and identifying changes in the neuromuscular system in osteoarthritis, this year's ACR/ARHP Annual Meeting also offered several additional sessions that addressed more off-the-beaten-path topics.

During his session at the 2011 ACR/ARHP Annual Meeting, A. Vania Apkarian, PhD, professor of physiology, department of physiology, Northwestern University Feinberg School of Medicine, summarized recent research on pain perception that shows distinct regional changes in the brains of patients suffering from chronic painful conditions such as osteoarthritis (OA).

Apkarian noted that his research has shown that the anatomy of the brain changes profusely in the osteoarthritis pain patient, and said that his research has led him to believe there is a "very specific signature in the brain that distinguishes the OA patient from other chronic pain patients."

For their research, Apkarian and his team used a mechanical device to apply pressure to the knees of patients, who provided feedback on the extent of pain. They also used functional MRI (fMRI) to identify which parts of the brain are activated, and to what extent, during the painful stimulus. This allowed researchers to capture the time variability of the pain and the intensity of the stimulus applied.

He said that psychophysically, pressure pain ratings did not differ between OA patients and healthy subjects. There was also no difference between knees in patients with OA. Thus, he said that "the clinical assumption that the knee joint in OA patient is sensitized to pain turns out not to be true."

Is There a Unique “Brain Signature” Associated with Osteoarthritis and Other Chronic Pain Conditions?

Researchers using fMRI make the controversial claim that the unique structural changes observed in the brains of patients with osteoarthritis can be used to predict placebo response.

This and other research, said Apkarian, shows that different pain conditions, such as osteoarthritis, produce distinct brain activity, and each has a unique signature in the brain. For example, he said studies of regional gray matter density shows decreased gray matter in specific regions in patients with chronic back pain (CBP). He said that you can see different patterns of this for different chronic pain conditions, and that chronic pain is associated with functional behavior and chemical changes in the cortex. In addition, Apkarian told the audience that imaging studies show that there is increased interaction between regions of the brain in OA patients compared to healthy subjects. "There is massive plasticity of the brain that is specific to chronic pain patients," he said.

Because of these changes, he said that researchers can look at the single parameter of whole brain reorganization to distinguish between OA patients and healthy patients with 90% accuracy. The longer the patient has lived with chronic OA pain, the greater the reorganization.

Apkarian next described results from a double-blind, placebo-controlled brain imaging study involving 30 patients with chronic back pain: half of them received a 5% lidocaine patch, and half received placebo. All patients were scanned with fMRI for spontaneous pain at baseline, at six hours post-treatment, and after two weeks of patch use. The researchers reported no difference in pain perception between treatments. By comparing imaging results of patients who responded to treatment to imaging of nonresponders after 2 weeks, Apkarian said that the research team was able to predict with 80% accuracy at baseline which patients will respond to placebo after two weeks.

In another study, researchers gave placebo to 17 osteoarthritis patients, and conducted fMRI scans at baseline and two weeks post-treatment, then followed the patients two more weeks for pain. After two weeks, there were eight responders to placebo, and nine nonresponders. Responders reported a 50% decrease in pain, vs. no real difference in nonresponders. Pain increased after patients stopped taking placebo.

Investigating whether the same brain network identified in the chronic back pain study was also predictive of placebo response in these patients with OA, Apkarian’s team compared brain connectivity at baseline between the groups and identified a second "brain circuit" that differentiates and predicts OA placebo responders from nonresponders with 95% accuracy.

In closing, Apkarian said that chronic pain imparts a specific signature on the brain, which depends on the experiential history of the condition and reorganizational mechanisms of the peripheral and central nerve systems. He said that there are functional and anatomic profiles that distinguish between acute and various chronic pain conditions, and that it is possible to use the specificity of this signature for each clinical condition to help predict placebo response in patients.

During her presentation on "Arthritis and Traditional Chinese Medicine" at the 2011 ACR/ARHP Annual Meeting, Chenchen Wang, MD, MSc, associate professor of medicine, Tufts Medical Center, Tufts University School of Medicine, briefly compared and contrasted the basic tenets and approaches of Chinese and Western medicine, and reviewed evidence for the efficacy of tai chi for treating fibromyalgia, arthritis, and other painful rheumatic conditions.

The Mind-Body Connection: The Use of Tai Chi to Treat Arthritis and Other Painful Rheumatic Diseases

With more patients and practitioners expressing interest in non-Western modes of healing and other complementary and alternative forms of medicine, researchers are studying whether methods like tai chi are effective in treating arthritis and other painful conditions.

Dr. Wang noted that in her opinion, traditional Chinese medicine is empirical, whereas Western medicine is more experimental and based on the animal model. She said that Chinese medicine is a "whole body system," while practitioners of Western medicine tend to focus on individual body systems. The attempt to achieve "Man-nature harmony" in Chinese medicine results in "whole and multifactorial interaction in medicine, particularly in terms of syndrome differentiation," with practitioners seeking to “heal the person with illness.” She contrasted this approach with the Western approach of "dealing with local structural problems with causalities, particularly with the disease itself" and "treating the illness of the person."

Wang noted that research has shown beneficial mind-body effects in patients who use tai chi for chronic pain, and that the interactions between the brain, mind, body, and emotions facilitated by tai chi may enhance patients’ capacity for self-care. In one study ("A Randomized Trial of Tai Chi for Fibromyalgia" http://www.ncbi.nlm.nih.gov/pubmed/20818876), Wang and colleagues "conducted a single-blind, randomized trial of classic Yang-style tai chi as compared with a control intervention consisting of wellness education and stretching for the treatment of fibromyalgia." Patients in both groups participated in one-hour sessions, twice a week, for 12 weeks. The researchers measured the change in participants' Fibromyalgia Impact Questionnaire (FIQ) scores after 12 weeks, and again after 24 weeks. Patients were also administered the Medical Outcomes Study 36-Item Short-Form Health Survey to measure changes in quality of life scores. The patients in the tai chi group "had clinically important improvements in the FIQ total score and quality of life" that were maintained at 24 weeks.

In another study that looked at the effect of tai chi on osteoarthritis ("Tai Chi is Effective in Treating Knee Osteoarthritis: A Randomized Controlled Trial" http://www.ncbi.nlm.nih.gov/pubmed/19877092), Chang and colleagues "conducted a prospective, single-blind, randomized controlled trial of 40 individuals with symptomatic tibiofemoral OA." Participants were randomized to one-hour tai chi sessions or "attention control (wellness education and stretching)" sessions twice weekly for 12 weeks. The researchers measured participants' Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores after 12 weeks, along with "WOMAC function, patient and physician global assessments, timed chair stand, depression index, self-efficacy scale, and quality of life." They repeated the measurements after 24 and 48 weeks. They reported that, compared with the controls, patients assigned to tai chi exhibited "significantly greater improvement" in WOMAC pain scores, WOMAC physical function, patient global visual analog scale, physician global VAS, chair stand time, Center for Epidemiologic Studies Depression Scale, self-efficacy score, and Short Form 36 physical component summary. These results led Wang and colleagues to conclude that tai chi "reduces pain and improves physical function, self-efficacy, depression, and health-related quality of life for knee OA."

She said that these and other studies support the contention that tai chi is a "safe and enjoyable exercise with high adherence that is effective for the treatment of chronic pain, and improves physical function, sleep quality, depression, and quality of life in some people with arthritis and chronic pain."

The Debate Over Medical Marijuana Continues

Although there is some evidence showing treatment with medical marijuana can benefit patients with arthritis, chronic pain, and other conditions, there are also serious concerns over quality control, non-standardized dosing, and other potential safety risks.

The light-hearted debate between Stuart Silverman, MD, and Arthur Kavanaugh, MD, during the "Joints for Joints: Medical Marijuana is Useful for Treating Rheumatic Disease" session at the 2011 ACR/ARHP Annual Meeting featured music clips, humorous Photoshopped images of the presenters, and plenty of marijuana-focused quips and double entendres. It also covered several serious issues associated with the proliferation in use of medical marijuana for treating rheumatic diseases and a range of chronic painful conditions.

Silverman, who is clinical professor of medicine at University of California, Los Angeles, and the medical director of OMC Clinical Research Center, argued against the position that medical marijuana is an useful treatment, pointing out that although there is some showing some clinical benefits, they are outweighed by the risks associated with medical marijuana and the lack of solid information available for physicians and patients. "If we’re going to prescribe it, we need to know what it is, and how it works," he said.

In addition to noting the lack of guidelines for physicians who recommend medical marijuana and the variability in practice, Silverman said that the biggest problem with medical marijuana is that, most of the time, physicians and patients don’t know what they’re getting from the dispensaries. He showed the audience several examples of the ads and menus of products offered by dispensaries in California, most of which had given silly, euphemistic names to the marijuana strains (“Green Dream,” “Orange Kush,” “AK47,” etc) that provided no useful information. “How do the clinics know the potency of what they’re offering? How do they check the THC content? These product names are just marketing gimmicks,” he said.

has shown that there is a tremendous amount of product variability in medical marijuana, along with frequent mold and fungus contamination, wide variability in THC content, lack of transparency from suppliers, and other variables that together make it difficult for patients and physicians to make informed prescribing decisions. Silverman said that often, patients rely on the product recommendations from the dispensaries and collectives selling the products. Most patients do not know about species differences, or about the risk of contamination.

The variable methods of medical marijuana delivery also introduce a large degree of uncertainty, making accurate dosing a challenge. For example, Silverman noted that edible marijuana products contain variable levels of active ingredient, and are absorbed into the system much slower than inhaling. Smoking remains the most common and easiest route of delivery for medical marijuana, with vaporizers being the preferred delivery method for many patients. But the actual amount of active ingredient delivered is highly variable, based on smoking style. Smoking, of course, carries with it its own additional health risks; smoke from a joint or pipe contains the same constituents (apart from nicotine) as cigarette smoke. Plus, Silverman observed that "smoking results in rapid onset of effect, but with high serum levels of the active ingredient over short intervals, which doesn’t make it a good candidate for treating chronic pain."

Medical marijuana has a wide range of side effects, with a highly variable incidence. In order to prescribe this medically, physicians must determine if its therapeutic effects outweigh the potential harmful side effects. Silverman concluded that although medical marijuana might have some potential benefits, it is “not ready for primetime” until serious issues regarding dosing standardization, quality control, potential adverse effects, addiction and dependence prevention, and provider training are addressed.

In the November 2010 issue of Pain Management (http://bit.ly/ufMnln), editorial board member Steve Passik, PhD, and co-author Sharang Tickoo wrote that it was their belief that many politicians who supported legalizing medical marijuana were “using physicians as a Trojan horse” to appease supporters of full legalization. In their view, “Medical marijuana is a compromise that hurts the already troubled image of the pain doctor and threatens pain management.” They concluded that “if Americans want legal marijuana then it should be legal (as long as some of the revenue generated is targeted at improved substance-abuse treatment for those vulnerable individuals who might be harmed by this increased access). If, once marijuana is legal, there is a desire to develop special access programs for the medically ill or even grow particularly pure or potent plants, so be it. Perhaps better safety and efficacy studies would follow. The present confusion between medical marijuana laws on a state level (which of course is not truly legal) and federal laws is the worst of both worlds.”

Arthur Kavanaugh, MD, professor of medicine, division of rheumatology, allergy, immunology, University of California, San Diego, arguing the “pro” position in this debate, offered several examples of studies showing the benefits of medical marijuana for treating musculoskeletal pain and other rheumatic conditions. He also said that there is some strong in vitro evidence for the anti-inflammatory effects of marijuana. Kavanaugh was more sanguine about the safety and efficacy issues associated with medical marijuana, noting that we have a mountain of anecdotal evidence from thousands of years of medicinal and recreational use. He did agree with Silverman that it is vitally important to work to reduce the variability in active ingredient strength among the products and to improve patient and provider education. He speculated that these deficiencies may be due in large part to the degree to which politics in the US has hindered development and testing of medical marijuana.