The insular (IC) and cingulate cortices (CC) are critically involved in pain perception. Previously we demonstrated that fibromyalgia (FM) patients have greater connectivity between the insula and Default Mode Network at rest, and that changes in the degree of this connectivity were associated with changes in the intensity of ongoing clinical pain. Here we more thoroughly evaluate the degree of resting state connectivity to multiple regions of the IC in individuals with FM and healthy controls (HC). We also investigated the relationship between connectivity, experimental pain and current clinical chronic pain. Functional connectivity was assessed using resting state functional magnetic resonance imaging in 18 FM patients and 18 age- and sex-matched HC using pre-defined seed regions in the anterior, middle and posterior IC. FM patients exhibited greater connectivity between: (1) right mid IC and right mid/posterior CC and right mid IC; (2) right posterior IC and the left CC; and (3) right anterior IC and left superior temporal gyrus. HCs displayed greater connectivity between: left anterior IC and the bilateral medial frontal gyrus/ACC; and left posterior IC and the right superior frontal gyrus. Within the FM group, greater connectivity between the IC and CC was associated with decreased pressure-pain thresholds. Perspective These data provide further support for altered resting-state connectivity between the IC and other brain regions known to participate in pain perception/modulation playing a pathogenic role in conditions such as FM. We speculate that altered IC connectivity is associated with the experience of chronic pain in individuals with fibromyalgia.

Background Amongst the most common chronic pain conditions, yet poorly understood, are temporomandibular disorders (TMDs), with a prevalence estimate of 3 – 15% for Western populations. Although it is increasingly acknowledged that central nervous system mechanisms contribute to pain amplification and chronicity in TMDs, further research is needed to unravel neural correlates that might abet the development of chronic pain. Objective The insular cortex (IC) and cingulate cortex (CC) are both critically involved in the experience of pain. The current study sought specifically to investigate IC-CC functional connectivity in TMD patients and healthy controls (HCs), both during resting state and during the application of a painful stimulus. Method Eight patients with TMD, and 8 age and sex matched healthy controls (HCs) were enrolled in the present study. FMRI data during resting state and during the performance of a pressure pain stimulus to the temple were acquired. Predefined seed regions were placed in the IC (anterior and posterior insular cortices) and the extracted signal was correlated with brain activity throughout the whole brain. Specifically we were interested whether TMD patients and HCs would show differences in IC – CC connectivity, both during resting state and during the application of a painful stimulus to the face. Results As a main finding functional connectivity analyses revealed an increased functional connectivity between the left anterior IC and pregenual ACC in TMD patients, during both resting state and applied pressure pain. Within the patient group there was a negative correlation between the anterior IC - ACC connectivity and clinical pain intensity as measured by a VAS. Conclusions Since the pregenual region of the ACC is critically involved in antinociception, we hypothesize that an increase in anterior IC – ACC connectivity is indicative of an adaptation of the pain modulatory system early in the chronification process.