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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurol. | doi: 10.3389/fneur.2019.01110

Reduced glutamate in the medial prefrontal cortex is associated with emotional and cognitive dysregulation in people with chronic pain

Brooke Naylor1, 2,  Negin Hesam-Shariati2, James McAuley2, 3,  Simon Boag1,  Toby Newton-John4,  Caroline Rae2, 3 and  Sylvia M. Gustin2, 5*
  • 1Macquarie University, Australia
  • 2Neuroscience Research Australia, Australia
  • 3University of New South Wales, Australia
  • 4University of Technology Sydney, Australia
  • 5School of Psychology, University of New South Wales, Australia

A decrease in glutamate in the medial prefrontal cortex (mPFC) has been extensively found in animal models of chronic pain. Given that the mPFC is implicated in emotional appraisal, cognition and extinction of fear, could a potential decrease in glutamate be associated with increased pessimistic thinking, fear and worry symptoms commonly found in people with chronic pain? To clarify this question, 19 chronic pain subjects and 19 age- and gender-matched control subjects without pain underwent magnetic resonance spectroscopy. Both groups also completed the Temperament and Character, the Beck Depression and the State Anxiety Inventories to measure levels of harm avoidance, depression and anxiety, respectively. People with chronic pain had significantly higher scores in harm avoidance, depression and anxiety compared to control subjects without pain. High levels of harm avoidance are characterised by excessive worry, pessimism, fear, doubt and fatigue. Individuals with chronic pain showed a significant decrease in mPFC glutamate levels compared to control subjects without pain. In people with chronic pain mPFC glutamate levels were significantly negatively correlated with harm avoidance scores. This means that the lower the concentration of glutamate in the mPFC, the greater the total scores of harm avoidance. High scores are associated with fearfulness, pessimism and fatigue-proneness. We suggest that chronic pain, particularly the stress-induced release of glucocorticoids, induces changes in glutamate transmission in the mPFC, thereby influencing cognitive and emotional processing. Thus, in people with chronic pain, regulation of fear, worry, negative thinking and fatigue is impaired.

Keywords: Medial prefrontal cortex, Chronic Pain, spectroscopy, Glutamate, N-acetylaspartate, harm avoidance, emotional dysregulation

Received: 14 Mar 2019; Accepted: 03 Oct 2019.

Copyright: © 2019 Naylor, Hesam-Shariati, McAuley, Boag, Newton-John, Rae and Gustin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Sylvia M. Gustin, School of Psychology, University of New South Wales, Sydney, 2052, New South Wales, Australia,