The science of fibromyalgia

Abstract

Fibromyalgia (FM) is a common chronic widespread pain disorder. Our understanding of FM has increased substantially in recent years with extensive research suggesting a neurogenic origin for the most prominent symptom of FM, chronic widespread pain. Neurochemical imbalances in the central nervous system are associated with central amplification of pain perception characterized by allodynia (a heightened sensitivity to stimuli that are not normally painful) and hyperalgesia (an increased response to painful stimuli). Despite this increased awareness and understanding, FM remains undiagnosed in an estimated 75% of people with the disorder. Clinicians could more effectively diagnose and manage FM if they better understood its underlying mechanisms. Fibromyalgia is a disorder of pain processing. Evidence suggests that both the ascending and descending pain pathways operate abnormally, resulting in central amplification of pain signals, analogous to the "volume control setting" being turned up too high. Patients with FM also exhibit changes in the levels of neurotransmitters that cause augmented central nervous system pain processing; levels of several neurotransmitters that facilitate pain transmission are elevated in the cerebrospinal fluid and brain, and levels of several neurotransmitters known to inhibit pain transmission are decreased. Pharmacological agents that act centrally in ascending and/or descending pain processing pathways, such as medications with approved indications for FM, are effective in many patients with FM as well as other conditions involving central pain amplification. Research is ongoing to determine the role of analogous central nervous system factors in the other cardinal symptoms of FM, such as fatigue, nonrestorative sleep, and cognitive dysfunction.

FIGURE 1.

Pain sensitivity in the general population. From Rheum Dis Clin N Am, with permission from Elsevier.

FIGURE 2.

Neuroimages of regional cerebral blood flow in areas of the brain associated with pain processing in patients with fibromyalgia and controls. These images reflect responses to stimuli during pain scans. The effects of pressure applied to the left thumb sufficient to evoke a pain rating of 11 (moderate) are compared with the effects of innocuous pressure in patients with fibromyalgia (red) and controls (green), with overlapping activations in yellow. Significant increases in the functional magnetic resonance imaging signal (arrows) resulting from increases in regional cerebral blood flow are shown in standard space superimposed on an anatomic image of a standard brain. Similar pain intensities, produced by significantly less pressure in patients with FM, resulted in overlapping or adjacent activations in the contralateral primary somatosensory cortex (SI), inferior parietal lobule (IPL), secondary somatosensory cortex (SII), superior temporal gyrus (STG), insula, and putamen, as well as in the ipsilateral cerebellum. From Arthritis Rheum, with permission from John Wiley and Sons.

FIGURE 3.

Neural pathways and neurotransmitters that influence pain sensitivity. Adapted from Rheum Dis Clin N Am, with permission from Elsevier.