Lower Functional Connectivity of the Periaqueductal Gray Is Related to Negative Affect and Clinical Manifestations of Fibromyalgia

Abstract

Fibromyalgia (FM) syndrome is characterized by chronic widespread pain, muscle tenderness and emotional distress. Previous studies found reduced endogenous pain modulation in FM. This deficiency of pain modulation may be related to the attributes of chronic pain and other clinical symptoms experienced in patients with FM. Thus, we tested whether there is a link between the clinical symptoms of FM and functional connectivity (FC) of the periaqueductal gray (PAG), a key node of pain modulation. We acquired resting state 3T functional MRI (rsfMRI) data from 23 female patients with FM and 16 age- and sex- matched healthy controls (HC) and assessed FM symptoms with the Brief Pain Inventory (BPI), Fibromyalgia Impact Questionnaire (FIQ), Hospital Anxiety and Depression Scale (HADS) and Pain Catastrophizing Scale (PCS). We found that patients with FM exhibit statistically significant disruptions in PAG FC, particularly with brain regions implicated in negative affect, self-awareness and saliency. Specifically, we found that, compared to HCs, the FM patients had stronger PAG FC with the lingual gyrus and hippocampus but weaker PAG FC with regions associated with motor/executive functions, the salience (SN) and default mode networks (DMN). The attenuated PAG FC was also negatively correlated with FIQ scores, and positively correlated with the magnification subscale of the PCS. These alterations were correlated with emotional and behavioral symptoms of FM. Our study implicates the PAG as a site of dysfunction contributing to the clinical manifestations and pain in FM.

Effects of genetic deletion versus pharmacological blockade of the LPA1 receptor on depression-like behaviour and related brain functional activity

“…In the antagonist-treated group, the activation of the hippocampus was accompanied by augmented activity of the LHb, which has been correlated with aversive states ( Margolis and Fields, 2016 ), and might be at least part of the substrate responsible for the increased immobility time ( Yang et al, 2008 ). In addition, after the FST, a reduction in PAG activity was observed that could be linked to negative affect ( Miczek et al, 1999 ; Mickley et al, 2011 ; Coulombe et al, 2017 ). Conversely, in WT animals, stress engaged all the limbic and almost all extralimbic regions examined, except for the LHb.…”

Composite Pain Biomarker Signatures for Objective Assessment and Effective Treatment

“…Neuroimaging in human volunteers has identified regions of the brainstem that become active during the development and maintenance of capsaicin-induced central sensitization and secondary mechanical hyperalgesia, during somatic and visceral pain, and during post-opioid hyperalgesia (Lee et al, 2008;Zambreanu et al, 2005). Such altered activity (less inhibition and more facilitation) has been verified in multiple patient cohorts, such as migraine, fibromyalgia, osteoarthritic hip and knee pain, and, most recently, painful diabetic neuropathy (Coulombe et al, 2017;Gwilym et al, 2009;Harper et al, 2018;Mainero et al, 2011;Marciszewski et al, 2018;Segerdahl et al, 2018;Soni et al, 2018). Stratifying patients based upon the presence or absence of DPMS involvement may be a potential biomarker for predicting outcome to treatment/surgery.…”

Brain imaging tests for chronic pain: medical, legal and ethical issues and recommendations

“…A different approach is to measure the dynamic brain connectivity, which varies over time, to enable identification of connectivity patterns that vary with reported levels of ongoing pain. This approach has revealed changes in the default mode and salience brain networks in chronic pain states [107][108][109] . However, a potential confounding factor is the possibility that the judgement and reporting of ongoing pain causes a detectable change in brain processing.…”