What does the grey matter decrease in the medial prefrontal cortex reflect in people with chronic pain?

Background and Objective Alterations in the grey matter volume of several brain regions have been reported in people with chronic pain. The most consistent observation is a decrease in grey matter volume in the medial prefrontal cortex. These findings are important as the medial prefrontal cortex plays a critical role in emotional and cognitive processing in chronic pain. Although a logical cause of grey matter volume decrease may be neurodegeneration, this is not supported by the current evidence. Therefore, the purpose of this review was to evaluate the existing literature to unravel what the decrease in medial prefrontal cortex grey matter volume in people with chronic pain may represent on a biochemical and cellular level. Databases and Data Treatment A literature search for this topical review was conducted using PubMed and SCOPUS library. Search terms included chronic pain, pain, medial prefrontal cortex, anterior cingulate cortex, grey matter, neurochemistry, spectroscopy, magnetic resonance imaging, positron emission tomography, dendrite, neurodegeneration, glia, astrocyte, microglia, neurotransmitter, glutamate, GABA and different combinations of these terms. Results Adopting a stress model of chronic pain, two major pathways are proposed that contribute to grey matter volume decrease in the medial prefrontal cortex: (a) changes in dendritic morphology as a result of hypothalamic-pituitary axis dysfunction and (b) neurotransmitter dysregulation, specifically glutamate and gamma-Aminobutyric acid, which affects local microvasculature. Conclusion Our model proposes new mechanisms in chronic pain pathophysiology responsible for mPFC grey matter loss as alternatives to neurodegeneration. Significance It is unclear what the decrease in medial prefrontal cortex grey matter volume represents in chronic pain. The most attractive reason is neurodegeneration. However, there is no evidence to support this. Our review reveals nondegenerative causes of decreased medial prefrontal grey matter to guide future research into chronic pain pathophysiology.