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.

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