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J Neurosci. 2014 Mar 12;34(11):3969-75. doi: 10.1523/JNEUROSCI.5055-13.2014.

Enhanced medial prefrontal-default mode network functional connectivity in chronic pain and its association with pain rumination.

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Division of Brain, Imaging and Behaviour-Systems Neuroscience, Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada M5T 2S8, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada M5S 1A8, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada M5G 1G6, Mount Sinai Hospital Dental Clinic, Toronto, Ontario, Canada M5G 1X5, Department of Surgery, University of Toronto, Toronto, Ontario, Canada M5T 1P5, Department of Neuroscience, Physiology and Pharmacology, University College London, United Kingdom WC1E 6BT, Department of Physical Therapy, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel 3498838, and University of Toronto Centre for the Study of Pain, Toronto, Ontario, Canada M5T 1P8.


Rumination is a form of thought characterized by repetitive focus on discomforting emotions or stimuli. In chronic pain disorders, rumination can impede treatment efficacy. The brain mechanisms underlying rumination about chronic pain are not understood. Interestingly, a link between rumination and functional connectivity (FC) of the brain's default mode network (DMN) has been identified within the context of mood disorders. We, and others, have also found DMN dysfunction in chronic pain populations. The medial prefrontal cortex (mPFC) is a key node of the DMN that is anatomically connected with the descending pain modulatory system. Therefore, we tested the hypothesis that in patients with chronic pain, the mPFC exhibits abnormal FC related to the patient's degree of rumination about their pain. Seventeen patients with idiopathic temporomandibular disorder (TMD) and 17 age- and sex-matched healthy controls underwent resting state functional MRI, and rumination about pain was assessed through the rumination subscale of the Pain Catastrophizing Scale. Compared with healthy controls, we found that TMD patients exhibited enhanced mPFC FC with other DMN regions, including the posterior cingulate cortex (PCC)/precuneus (PCu) and retrosplenial cortex. We also found that individual differences in pain rumination in the chronic pain patients (but not in healthy controls) were positively correlated to mPFC FC with the PCC/PCu, retrosplenial cortex, medial thalamus, and periaqueductal/periventricular gray. These data implicate communication within the DMN and of the DMN with the descending modulatory system as a mechanism underlying the degree to which patients ruminate about their chronic pain.


TMD; connectivity; default mode; medial prefrontal cortex; pain; rumination

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