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

Brooke Naylor, Negin Hesam-Shariati, James H. McAuley, Simon Boag, Toby Newton-John, Caroline D. Rae, Sylvia M. Gustin*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    11 Citations (Scopus)
    15 Downloads (Pure)


    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 characterized 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.

    Original languageEnglish
    Article number1110
    Pages (from-to)1-13
    Number of pages13
    JournalFrontiers in Neurology
    Publication statusPublished - 3 Dec 2019

    Bibliographical note

    Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.


    • medial prefrontal cortex
    • chronic pain
    • spectroscopy
    • glutamate
    • N-acetylaspartate
    • harm avoidance
    • emotional dysregulation


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