Abstract
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.
Highlights
Brain morphological changes are known to occur in chronic pain [1, 2]
Two people with chronic pain suffered from trigeminal neuropathy (TNP), one person suffered from trigeminal post-herpetic neuralgia, and one individual had atypical trigeminal neuralgia assessed by the Liverpool Criteria [54]
We argue that the decline in medial prefrontal cortex (mPFC) NAA represents a decrease in mitochondrial activity rather than neuronal loss because [1] we found a reduction in mPFC glutamate which declines with decreased mitochondrial activity in a linear manner [69, 75, 76] and [2] we found a significant positive correlation between NAA and glutamate
Summary
Different types of chronic pain, e.g., nociceptive and neuropathic pain, differ in their pattern of gray matter changes [3,4,5], they show a substantial overlap in the medial prefrontal cortex (mPFC), where a decrease in gray matter volume has been widely demonstrated [2, 6,7,8,9]. We recently proposed that a decrease in mPFC gray matter volume reflects many changes, including vascular alterations caused by a change in metabolic activity, e.g., glutamate [10]. An alteration in mPFC glutamate levels has been shown in animal models of chronic pain but has never been reported in humans with chronic pain [12,13,14,15,16,17,18]. We would expect a decrease in mPFC glutamate in people with chronic pain
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