Queen’s University researcher Ian Gilron has uncovered a more effective way of treating fibromyalgia, a medical condition characterized by chronic widespread pain typically accompanied by fatigue, as well as sleep, mood and memory problems.

The results of the trial suggest that combining pregabalin, an anti-seizure drug, with duloxetine, an antidepressant, can safely improve outcomes in fibromyalgia, including not only pain relief, but also physical function and overall quality of life. Until now, these drugs have been proven, individually, to treat fibromyalgia pain.

“Previous evidence supports added benefits with some drug combinations in fibromyalgia,” says, Dr. Gilron (Anesthesiology, Biomedical Sciences). “We are very excited to present the first evidence demonstrating superiority of a duloxetine-pregabalin combination over either drug alone.”

Fibromyalgia was initially thought to be a musculoskeletal disorder. Research now suggests it’s a disorder of the central nervous system – the brain and spinal cord. Researchers believe that fibromyalgia amplifies painful sensations by affecting the level and activity of brain chemicals responsible for processing pain signals.

“The condition affects about 1.5 to 5 per cent of Canadians – more than twice as many women as men. It can have a devastating on the lives of patients and their families,” explains Dr. Gilron. “Current treatments for fibromyalgia are either ineffective or intolerable for many patients.”

This study is the latest in a series of clinical trials – funded by the Canadian Institutes of Health Research (CIHR) – that Dr. Gilron and his colleagues have conducted on combination therapies for chronic pain conditions. By identifying and studying promising drug combinations, their research is showing how physicians can make the best use of current treatments available to patients.

“The value of such combination approaches is they typically involve drugs that have been extensively studied and are well known to health-care providers,” says Dr. Gilron.

This new research was published in the journal Pain.

Dr. Gilron and his research team at Queen’s are members of the SPOR Network on Chronic Pain. The national network, funded under Canada’s Strategy for Patient-Oriented Research, directs new research, trains researchers and clinicians, increases access to care for chronic pain sufferers, and speeds up the translation of the most recent research into practice.

 Evidence suggests acupuncture reduces the symptoms of fibromyalgia, according to a Mayo Clinic study.

Fibromyalgia is a disorder considered disabling by many, and is characterized by chronic, widespread musculoskeletal pain and symptoms such as fatigue, joint stiffness and sleep disturbance. No cure is known and available treatments are only partially effective.

Mayo’s study involved 50 fibromyalgia patients enrolled in a randomized, controlled trial to determine if acupuncture improved their symptoms. Symptoms of patients who received acupuncture significantly improved compared with the control group, according to the study published in the June issue of Mayo Clinic Proceedings.

“The results of the study convince me there is something more than the placebo effect to acupuncture,” says David Martin, M.D., Ph.D., lead author of the acupuncture article and a Mayo Clinic anesthesiologist. “It affirms a lot of clinical impressions that this complementary medical technique is helpful for patients.”

Increasingly, patients are interested in pursuing complementary medicine techniques in conjunction with their mainstream medical care, Dr. Martin says. But often, such techniques lack scientific evidence to justify a patient’s expense and time.

The study lends credence to patients’ belief that nontraditional methods may improve their health. In Mayo’s trial, patients who received acupuncture to counter their fibromyalgia symptoms reported improvement in fatigue and anxiety, among other symptoms. Acupuncture was well tolerated, with minimal side effects.

Mayo’s acupuncture study is one of only three randomized and controlled studies involving fibromyalgia patients. Of the other studies, one found acupuncture to be helpful, while the other reported it was ineffective for pain relief.

Dr. Martin says Mayo’s study demonstrates that acupuncture is helpful, and also proves physicians can conduct a rigorous, controlled acupuncture study. Future research could help physicians understand which medical conditions respond best to acupuncture, how to apply it to best relieve symptoms, and how long patients can expect to their symptoms to decrease after each treatment.

People who have the common chronic pain condition fibromyalgia often report that they don’t respond to the types of medication that relieve other people’s pain. New research from the University of Michigan Health System helps to explain why that might be: Patients with fibromyalgia were found to have reduced binding ability of a type of receptor in the brain that is the target of opioid painkiller drugs such as morphine.

The study included positron emission tomography (PET) scans of the brains of patients with fibromyalgia, and of an equal number of sex- and age-matched people without the often-debilitating condition. Results showed that the fibromyalgia patients had reduced mu-opioid receptor (MOR) availability within regions of the brain that normally process and dampen pain signals – specifically, the nucleus accumbens, the anterior cingulate and the amygdala.

“The reduced availability of the receptor was associated with greater pain among people with fibromyalgia,” says lead author Richard E. Harris, Ph.D., research investigator in the Division of Rheumatology at the U-M Medical School’s Department of Internal Medicine and a researcher at the U-M Chronic Pain and Fatigue Research Center.

“These findings could explain why opioids are anecdotally thought to be ineffective in people with fibromyalgia,” he notes. The findings appear in The Journal of Neuroscience. “The finding is significant because it has been difficult to determine the causes of pain in patients with fibromyalgia, to the point that acceptance of the condition by medical practitioners has been slow.”

Opioid pain killers work by binding to opioid receptors in the brain and spinal cord. In addition to morphine, they include codeine, propoxyphene-containing medications such as Darvocet, hydrocodone-containing medications such as Vicodin, and oxycodone-containing medications such as Oxycontin.

The researchers theorize based on their findings that, with the lower availability of the MORs in three regions of the brains of people with fibromyalgia, such painkillers may not be able to bind as well to the receptors as they can in the brains of people without the condition.

Put more simply: When the painkillers cannot bind to the receptors, they cannot alleviate the patient’s pain as effectively, Harris says. The reduced availability of the receptors could result from a reduced number of opioid receptors, enhanced release of endogenous opioids (opioids, such as endorphins, that are produced naturally by the body), or both, Harris says.

The research team also found a possible link with depression. The PET scans showed that the fibromyalgia patients with more depressive symptoms had reductions of MOR binding potential in the amygdala, a region of the brain thought to modulate mood and the emotional dimension of pain.

The study subjects were 17 women with fibromyalgia and 17 women without the condition.

 

Areas of the brain responsible for pain processing and cognitive performance changed in fibromyalgia patients who exercised following a medication holiday, say researchers from Georgetown University Medical Center. They say the changes indicate brain functioning is more streamlined after an exercise intervention because less of the brain’s resources are devoted to processing bothersome fibromyalgia perceptions such as pain.

The study, presented at the Society of Neuroscience’s annual meeting, Neuroscience 2011, used functional MRI scans to assess changes in the brain. Researchers observed a decrease in brain activity in areas responsible for memory and pain control after fibromyalgia patients took part in an exercise regimen.

“The decreased brain activity we see in the area of cognition suggests that the brain is working more efficiently,” explains Brian Walitt, M.D. M.P.H., director of the Fibromyalgia Evaluation and Research Center at Georgetown University Medical Center and senior study author. “We also see less brain activity in areas responsible for pain processing which might be aiding that efficiency.” Walitt cautions that more research needs to be conducted before suggesting a change in clinical care for fibromyalgia.

Fibromyalgia is a medical disorder characterized by widespread pain, fatigue, disordered sleep, and cognitive changes. It is regarded as an interoceptive disorder in that it has no apparent cause, Walitt says. “In conditions like this, the body perceives something by mistake.” The pain is not psychosomatic, but is real and likely produced by the central nervous system, he says.

To that end, the research team used fMRI to “provide a definitive measure of cognitive functioning, so that we can more scientifically measure the effect of exercise,” says Manish Khatiwada, M.S., who will be presenting the results. “This is a novel approach to the study of fibromyalgia.” (Khatiwada is working in the laboratory of co-author John VanMeter, Ph.D., director of the Center for Functional and Molecular Imaging.)

For this study, the researchers enrolled eighteen women with fibromyalgia, and gave them a baseline fMRI to assess working memory and questionnaires about their well-being and pain while they were on medication. They then were told not to use their medications for a “washout” period, and had a second fMRI and memory testing. After six weeks, they had another assessment. The final scan was taken after the volunteers engaged in a six-week period of exercise, which involved three 30-minute sessions of aerobic exercise each week with a trainer.

Memory and pain typically worsen in patients after stopping their medication — which was the experience of patients in this study. After six weeks of exercise, however, patients reported an improvement in overall well-being. However, their performance in the memory task did not change significantly when compared to their baseline study measurements. Despite a change in memory test performance, brain activity in the memory task and pain processing areas of the brain decreased.

“What we see is a less interference by pain activity which could be contributing to the decrease in activity in the memory section. Basically, the brain is using less energy for the same task,” Walitt says.

 

Stressful or traumatic events experienced during pregnancy can have long-lasting effects on the fetus, yet these effects may not become apparent until many years later, according to a study suggesting that girls born of such pregnancies may be at greater risk for developing a painful muscle condition called fibromyalgia as adults.

The study, presented at the 6th International Congress of Neuroendocrinology (ICN 2006), shows how vulnerable a fetus is to “prenatal programming.” Indeed, animal studies presented at ICN 2006 indicate that a synthetic hormone commonly given to pregnant women at risk for delivering early can permanently affect the newborn’s neuroendocrine system and may have even more profound effects on those born in the next generation. ICN 2006 is being held at the David L. Lawrence Convention Center in Pittsburgh June 19 – 22.

Summaries of these studies’ findings follow:

Stress during pregnancy may put baby girls at later risk for fibromyalgia

New research suggests girls who were born following pregnancies that were encumbered by stressful life events may be at greater risk for developing fibromyalgia later in life. While little is known about the causes of fibromyalgia, a condition affecting mostly women and characterized by extreme fatigue and widespread muscle pain, the studies led by Dirk Hellhammer, Ph.D., professor of psychobiology at the University of Trier, Germany, indicate “prenatal programming” likely plays a role. Stress experienced during pregnancy can affect the development of the fetus’s adrenal gland, permanently limiting its capacity for producing adequate amounts of the hormone cortisol, he reports.

Compared to 100 healthy female control subjects, significantly more patients among the 93 women diagnosed with fibromyalgia reported their mothers had experienced profound stress during pregnancy, such as the loss of a partner, physical or emotional trauma or lack of social support. Moreover, of these patients born of such pregnancies, only the women had “blunted” cortisol response in a standardized measure of psychological stress, an observation that supported findings in animal studies. Furthermore, low cortisol levels were only observed in patients with a history of prenatal stress. While more study is needed, results collected so far provide strong evidence that girls may be at added risk for developing fibromyalgia if, while in the womb, they were exposed to higher than normal levels of cortisol produced by their mothers in response to stress.

Effects of steroid drug during pregnancy can span generations

A synthetic hormone commonly given to pregnant women at risk for delivering early not only can result in permanent changes to the newborn’s neuroendocrine system, but may have even greater effects on those born in the next generation, indicate results from animal studies.

Approximately 7 percent of pregnant women are treated with synthetic glucocorticoid to help hasten lung development when pre-term birth seems likely. Both animal and human clinical studies have shown the treatment could have long-term effects on neuroendocrine function and behavior. Using a guinea pig model, Stephen G. Matthews, Ph.D., professor, physiology, obstetrics & gynecology and medicine, University of Toronto, Faculty of Medicine, has shown that late-pregnancy exposure affects neurotransmitter systems – the brain’s primary communications vehicle – and makes fundamental changes to stress response mechanisms. Moreover, exposure in the womb to these synthetic hormones, which also have potent anti-inflammatory and immunosuppressive properties, can have life-long consequences. According to Dr. Matthews’ research, exposure affects the hypothalamic-pituitary-adrenal axis (HPA), which controls how the body responds to stress and is involved in regulation of energy balance and the immune system as well. Now, in more recent studies, his group is finding such effects extend to second generation offspring, in whom changes to HPA function and behavior are even greater than in those directly exposed. For instance, animals whose grandmothers were treated with glucocorticoids exhibit reduced levels of stress hormones and modified activity.