New research among patients with fibromyalgia (FM) shows evidence of parallel, independent neural processing pathways for sensory and affective pain, and points to the need for complementary and aggressive pharmacologic and non-pharmacologic treatment strategies in affected patients.¹

"The data from our study are consistent with clinical trials that suggest that if an individual has both pain and depression, that both must be treated," study author Daniel J. Clauw, MD, rheumatologist and assistant dean for clinical and translational research at the University of Michigan in Ann Arbor, tells CIAOMed.

The investigators note that the independent processing of sensory and affective pain is reflected in the differing effects of dissimilar classes of antidepressant medications. For example, tricyclic antidepressants provide some degree of analgesia, while selective serotonin reuptake inhibitors do not.

"Because some antidepressants also happen to act as analgesics, some healthcare providers feel that treating depression alone should be enough, but physicians must recognize depression and treat it as a separate problem, just as if a patient had another set of commonly co-occurring conditions, such as diabetes and hypertension," says Dr. Clauw, who is also director of Chronic Pain and Fatigue Research Center and the Center for the Advancement of Clinical Research at the University of Michigan.

While, at present, there is no specific therapy approved for the treatment of FM, a new clinical trial suggests that pregabalin, a novel α₂-β ligand, shows considerable promise for treating the pain, disturbed sleep, and fatigue of FM.²

In the first study of 53 FM patients and 42 controls, a subset of patients who underwent MRI demonstrated that significantly less applied pressure was required to initiate pain-related neuronal activation in the FM group, compared with healthy volunteers. This heightened sensitivity applied to FM patients in general, regardless of whether they had been diagnosed with major depressive disorder (MDD) or reported any depressive symptoms.

Furthermore, researchers found only a weak correlation between the sensory regions associated with chronic pain and the affective or emotional regions associated with depression. "The present results support the independence of multiple processing networks and confirm that specific cortical regions, particularly the anterior insula, may integrate the output of these separate networks and serve to process an individual's overall sensory/emotional experience," the investigators report.

Specifically, pain was associated with changes in the primary and secondary somatosensory cortices, while depression and MDDs affected the amygdale and contralaetal anterior insula, the study showed.

To arrive at their findings, researchers assessed the severity of chronic pain and depression in FM patients through interviews, questionnaires, and measurement scales. The following day, FM patients and control subjects participated in pressure-pain sensitivity assessments involving the application of pressure to a thumbnail. Moreover, all subjects underwent MRI scans, before, during, and after the pressure-sensitivity sessions.

FM patients were required to discontinue antidepressant medications 4 weeks prior to the start of study and refrain from using any pain medication, including over-the-counter analgesics, 3 days before the beginning of the trial.

 

Novel agent reduces pain, improves sleep in FM

In a double-blind randomized controlled trial of 529 FM patients, pregabalin 450 mg/day reduced the symptoms of pain, disturbed sleep, and fatigue, compared with placebo. Moreover, the agent was well-tolerated and improved global measures and health-related quality of life, according to findings in the April 2005 issue of Arthritis & Rheumatism.

Specifically, FM patients who took 450 mg/day of pregabalin had significantly less pain compared with those who received placebo. Twenty-nine percent of patients in this group had >50% improvement in pain at the endpoint versus 13% in the placebo group. Moreover, pregabalin at 300 and 450 mg/day was associated with significant improvements in sleep quality, fatigue, and global measures of change, while 450 mg/day improved several domains of health-related quality of life.

The most frequent adverse events reported in the study were dizziness and somnolence, and rates of discontinuation due to adverse events were similar across all four treatment groups. In this study, patients received placebo or 150, 300, and 450 mg/day pregabalin.

"To demonstrate improvements in the core symptoms of fibromylagia syndrome (FMS) - pain, sleep and fatigue - represents an important advance, particularly as there are no approved treatment for this condition," lead study author Leslie J. Crofford, MD, rheumatologist at the University of Kentucky in Lexington, notes in a statement accompanying the release of the trial. "FMS is highly debilitating for patients and difficult to treat, and we are in need of new treatment options that are both effective and well tolerated," she adds. "These data are highly encouraging because pregabalin was shown to provide significant relief from the most troublesome symptoms for patients."

Dr. Clauw agrees. "[Pregablin] is one of several promising compounds currently being studied in FM," he says. "It is possible, if not likely, that within several years there may be several drugs that are specifically approved for use in FM."

References:

1. Giesecke T, Gracely RH, Williams DA, et al. The relationship between depression, clinical pain, and experimental pain in a chronic pain cohort. Arthritis Rheum. 2005;52:1577-1584.
2. Crofford LJ, Rowbotham MC, Mease PJ, et al. Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2005;52:1264-1273.