Abstract
Chronic pain patients frequently develop and suffer from mental comorbidities such as depressive mood, impaired cognition, and other significant constraints of daily life, which can only insufficiently be overcome by medication. The emotional and cognitive components of pain are processed by the medial prefrontal cortex, which comprises the anterior cingulate cortex, the prelimbic, and the infralimbic cortex. All three subregions are significantly affected by chronic pain: magnetic resonance imaging has revealed gray matter loss in all these areas in chronic pain conditions. While the anterior cingulate cortex appears hyperactive, prelimbic, and infralimbic regions show reduced activity. The medial prefrontal cortex receives ascending, nociceptive input, but also exerts important top-down control of pain sensation: its projections are the main cortical input of the periaqueductal gray, which is part of the descending inhibitory pain control system at the spinal level. A multitude of neurotransmitter systems contributes to the fine-tuning of the local circuitry, of which cholinergic and GABAergic signaling are particularly emerging as relevant components of affective pain processing within the prefrontal cortex. Accordingly, factors such as distraction, positive mood, and anticipation of pain relief such as placebo can ameliorate pain by affecting mPFC function, making this cortical area a promising target region for medical as well as psychosocial interventions for pain therapy.
Highlights
Functional magnetic resonance imaging studies in both humans and rodents have shown that there is not a single brain structure responsible for pain perception, but that different cortical, subcortical, and associative brain regions are activated during a painful stimulus [1]
This review aims to dissect the main local circuitry, including transmitter systems, together with input and output connectivity of medial prefrontal cortex (mPFC) subregions and their importance for affective pain processing and the mental comorbidities frequently associated with chronic pain disorders
The selective ablation of astrocytes inhibits long-term facilitation associated with inflammatory pain and relieves escape avoidance behavior, which stresses their functional importance for pain processing in the anterior cingulate cortex (ACC) [117,118]
Summary
Functional magnetic resonance imaging (fMRI) studies in both humans and rodents have shown that there is not a single brain structure responsible for pain perception, but that different cortical, subcortical, and associative brain regions are activated during a painful stimulus [1]. The mPFC is primarily known for its prominent role in attention, working memory, and goal-directed behavior [20] It provides top-down regulation of sensory and affective processes, including inhibition of both sensory and affective pain signals by descending projections to the various brain and spinal cord regions: its projections are the main cortical input of the PAG, which is part of the descending inhibitory pain control system at the spinal level [21,22,23]. This review aims to dissect the main local circuitry, including transmitter systems, together with input and output connectivity of mPFC subregions and their importance for affective pain processing and the mental comorbidities frequently associated with chronic pain disorders
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