The contribution of sensory system functional connectivity reduction to clinical pain in fibromyalgia.

Fibromyalgia typically presents with spontaneous body pain with no apparent cause and is considered pathophysiologically to be a functional disorder of somatosensory processing. We have investigated potential associations between the degree of self-reported clinical pain and resting-state brain functional connectivity at different levels of putative somatosensory integration. Resting-state functional magnetic resonance imaging was obtained in 40 women with fibromyalgia and 36 control subjects. A combination of functional connectivity-based measurements were used to assess (1) the basic pain signal modulation system at the level of the periaqueductal gray (PAG); (2) the sensory cortex with an emphasis on the parietal operculum/secondary somatosensory cortex (SII); and (3) the connectivity of these regions with the self-referential "default mode" network. Compared with control subjects, a reduction of functional connectivity was identified across the 3 levels of neural processing, each showing a significant and complementary correlation with the degree of clinical pain. Specifically, self-reported pain in fibromyalgia patients correlated with (1) reduced connectivity between PAG and anterior insula; (2) reduced connectivity between SII and primary somatosensory, visual, and auditory cortices; and (3) increased connectivity between SII and the default mode network. The results confirm previous research demonstrating abnormal functional connectivity in fibromyalgia and show that alterations at different levels of sensory processing may contribute to account for clinical pain. Importantly, reduced functional connectivity extended beyond the somatosensory domain and implicated visual and auditory sensory modalities. Overall, this study suggests that a general weakening of sensory integration underlies clinical pain in fibromyalgia.