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.

Recent studies have suggested that most people who have been diagnosed with fibromyalgia by physicians may not actually have the condition. A new Arthritis Care & Research study found that overall agreement between clinicians’ diagnosis of fibromyalgia and diagnosis by published criteria is only fair.

For the study, 497 patients visiting a rheumatology clinic completed a health assessment questionnaire as well as a questionnaire that assessed fibromyalgia diagnostic variables used by the American College of Rheumatology. Patients were also evaluated and diagnosed by rheumatology clinicians.

Of the 497 patients, 121 (24.3 percent) satisfied fibromyalgia criteria while 104 (20.9 percent) received a clinician’s diagnosis of fibromyalgia. The agreement between clinicians and criteria was 79.2 percent; however, agreement beyond chance was only fair. Physicians failed to identify 60 (49.6 percent) of criteria-positive patients and incorrectly identified 43 (11.4 percent) of criteria-negative patients.

“We have recently studied the same issue in 3,000 primary care patients and found about the same results. Therefore, our conclusions are secure,” said lead author Dr. Frederick Wolfe, of the National Data Bank for Rheumatic Diseases.

In an accompanying editorial Dr. Don Goldenberg, of Oregon Health & Science University, noted that to conclude that expert physicians often misdiagnose fibromyalgia implies that published criteria are superior to expert clinical judgement for the diagnosis of individual patients. He stressed that this fails to account for many of the variables present in clinical encounters, including time spent in evaluating and categorizing each patient’s multiple symptoms. “The diagnostic gold standard for fibromyalgia will continue to be the rheumatologist’s expert opinion, not classification criteria, no matter how well-refined and intentioned,” he wrote. “This is the only way to capture the variability and severity of inter-related symptoms as they play out over time.”

New research indicates that a disruption of brain signals for reward and punishment contributes to increased pain sensitivity, known as hyperalgesia, in fibromyalgia patients. Results published in Arthritis & Rheumatism, a journal of the American College of Rheumatology, suggest that this altered brain processing might contribute to widespread pain and lack of response to opioid therapy in patients with fibromyalgia.

Fibromyalgia is a chronic, musculoskeletal syndrome characterized by widespread joint and muscle pain along with other symptoms such as fatigue, sleep disturbances, and cognitive difficulty. Previous research estimates that fibromyalgia affects 3.4% of women and 0.5% of men in the U.S. Prevalence of this pain disorder increases with age, affecting more than 7% of women between 60 and 79 years of age. 

“In patients with fibromyalgia there is an alteration in the central nervous system pain processing and a poor response to topical pain treatments, trigger point injections and opioids,” said lead author Dr. Marco Loggia from Massachusetts General Hospital and Harvard Medical School in Boston. “Our study examines the disruption of brain function involved in the individual experience of pain anticipation and pain relief.” 

For the present study, the research team enrolled 31 patients with fibromyalgia and 14 healthy controls. Functional magnetic resonance imaging (MRI) and cuff pressure pain stimuli on the leg were performed on all subjects. During the MRI, participants received visual cues alerting them of impending pain onset (pain anticipation) and pain offset (relief anticipation). 

Results show that during pain anticipation and relief, fibromyalgia patients displayed less robust response within brain regions involved in sensory, affective, cognitive and pain regulating processes. The ventral tegmental area (VTA)—a group of neurons in the center of the brain involved in the processing of reward and punishment—displayed activation during pain anticipation and stimulation, but deactivation during anticipation of relief in healthy controls. In contrast, VTA responses during periods of pain, and anticipation of pain and relief, in fibromyalgia patients were significantly reduced or inhibited. 

Dr. Loggia concludes, “Our findings suggest that fibromyalgia patients exhibit altered brain responses to punishing and rewarding events, such as expectancy of pain and relief of pain. These observations may contribute to explain the heightened sensitivity to pain, as well as the lack of effectiveness of pain medications such as opioids, observed in these patients. Future studies should further investigate the neurochemical basis underlying these dysfunctions.”