Enhanced Medial Prefrontal-Default Mode Network Functional Connectivity in Chronic Pain and Its Association with Pain Rumination

Abstract

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.

HIV Distal Neuropathic Pain Is Associated with Smaller Ventral Posterior Cingulate Cortex

“…That is rumination about non-pain related issues may function to inhibit the experience of pain [70]. This possible antinociceptive role for the PCC is consistent with the PCC participating in attentional disengagement from painful experiences during mind wandering [69,73,74]. A proposed mechanism for the PCC participating in antinociception may involve the default mode network circuit (connectivity between the PCC and medial prefrontal cortex) [37] interacting with descending analgesia brain circuits (connectivity between the periaqueductal gray matter and the rostral ventral medulla) [69,74,75].…”

Individual Differences in Temporal Summation of Pain Reflect Pronociceptive and Antinociceptive Brain Structure and Function

“…The resting-state fMRI data were preprocessed using methods and tools previously described in detail (Kucyi et al, 2013(Kucyi et al, , 2014. Using FSL v5.0 (Jenkinson et al, 2012), the fMRI Expert Analysis Tool (FEAT) was used on each subject's fMRI image to remove the first four volumes, extract the brain using the Brain Extract Tool (BET), correct for motion using the Functional MRI of the Brain (FMRIB) Linear Image Restoration Tool (FLIRT) with Motion Correction, and perform linear registration to both subject's T1-weighted anatomical image [six degrees of freedom (DOFs)] and standard MNI152 2 mm space (12 DOFs) using FLIRT.…”

“…To interrogate this concept, we examined resting state functional connectivity (FC) and cortical thickness of brain regions implicated in pain perception and its modulation, known as the "pain connectome" (Kucyi and Davis, 2015), in relation to individual differences in temporal summation of pain (TSP). TSP refers to the perception of increasing pain in response to repeated noxious stimuli delivered at a frequency of Ն0.33 Hz, and is the perceptual correlate of "wind-up" in the spinal dorsal horn (Mendell, 1966;Price et al, 1977).…”

“…It has been suggested that ascending processing of TSP in the cortex is mediated by Brodmann area (BA) 3a, but not BA 3b or 1 of the primary somatosensory cortex (S1; Vierck et al, 2013). However, other brain regions implicated in pain processing, such as the secondary somatosensory cortex (S2), anterior/midcingulate cortex (ACC/MCC), prefrontal cortex (PFC), and insula (Davis and Moayedi, 2013), may also play a role in mediating TSP (Staud et al, 2007).…”

Rumination modulates stress and other psychological processes in fibromyalgia

“…There are limited studies of neurophysiological processes in patients with chronic pain who have high levels of rumination. One study in such patients with temporomandibular disorder demonstrated dysfunction of the default mode network and its interaction with the descending pain modulatory system (28). This neural connectivity change, linking abnormal thought patterns to biological outcomes in the pain pathways, may have significant relevance to FM.…”