Impaired functioning of the brain's ability to process pain stimuli may negatively affect how people with fibromyalgia experience pain, according to new research. The research also shows that abnormal pain signal processing is associated with reduced opioid receptor binding, and these findings suggest that the brain's normal pain-inhibiting processes malfunction in fibromyalgia patients.
This study is the first to demonstrate the connection between μ-opioid receptor binding and the brain's response to the pain of fibromyalgia, said lead investigator Richard Harris, PhD, assistant professor in the Department of Anesthesiology and research assistant professor in the Department of Internal Medicine, University of Michigan, Ann Arbor. "In fibromyalgia patients, the main inhibitory mechanisms are not working correctly, specifically the opioid receptors within the brain," he said during his presentation at the 2012 annual meeting of the American College of Rheumatology (abstract 2450).
The investigators used functional magnetic resonance imaging to measure changes in blood flow in the brains of 18 female patients with fibromyalgia after they received a painful stimulus, administered to the thumb in varying intensity, and measured by the Short-Form McGill Pain Questionnaire. The researchers also measured μ-opioid receptor binding by positron emission tomography scanning. None of the patients had received opioids prior to the study, which was conducted between 2008 and 2012. The study cohort received acupuncture and placebo acupuncture for reduction of pain before and after the tests for the brain's response to pain and the binding of μ-opioid receptors.
A negative correlation was seen between the change in blood oxygenation level–dependent (BOLD) signal and the μ-opioid receptor binding in several regions of the brain involved in processing and controlling pain. These included the right posterior insula (R= –0.82; P=0.0004), left medial insula (R= –0.82; P=0.0003), left orbital frontal cortex (R= –0.75; P=0.0004) and right amygdala (R= –0.68; P=0.002).
Positive correlations also were found in the right dorsolateral prefrontal cortex (R=0.66;P=0.003), posterior cingulate (R=0.62; P=0.006) and the right putamen (R=0.72; P=0.0008).
"When opioid receptor binding went down, the evoked brain pain response went up in key brain regions that are involved in pain processing, such as the insula and amygdala," Dr. Harris said. He proposed two possible explanations: either the receptors were downregulated or activating the receptors actually caused pain.
Dr. Harris found the study results to be somewhat paradoxical. "We found that fibromyalgia patients either have too few receptors in their brains, or the receptors themselves, when they get activated, are causing pain instead of lessening pain. It is possible that opioids are not the best treatment for fibromyalgia and may even worsen symptoms," he added.
"This study may explain why patients with fibromyalgia do not respond to narcotics," said Kathryn Dao, MD, associate director of rheumatology research at Baylor Research Institute, in Dallas. "Further studies would help define if the same aberration in the pain signaling pathway is responsible for other chronic pain conditions."