Role of the Prefrontal Cortex in Pain Processing

Abstract

The prefrontal cortex (PFC) is not only important in executive functions, but also pain processing. The latter is dependent on its connections to other areas of the cerebral neocortex, hippocampus, periaqueductal gray (PAG), thalamus, amygdala, and basal nuclei. Changes in neurotransmitters, gene expression, glial cells, and neuroinflammation occur in the PFC during acute and chronic pain, that result in alterations to its structure, activity, and connectivity. The medial PFC (mPFC) could serve dual, opposing roles in pain: (1) it mediates antinociceptive effects, due to its connections with other cortical areas, and as the main source of cortical afferents to the PAG for modulation of pain. This is a 'loop' where, on one side, a sensory stimulus is transformed into a perceptual signal through high brain processing activity, and perceptual activity is then utilized to control the flow of afferent sensory stimuli at their entrance (dorsal horn) to the CNS. (2) It could induce pain chronification via its corticostriatal projection, possibly depending on the level of dopamine receptor activation (or lack of) in the ventral tegmental area-nucleus accumbens reward pathway. The PFC is involved in biopsychosocial pain management. This includes repetitive transcranial magnetic stimulation, transcranial direct current stimulation, antidepressants, acupuncture, cognitive behavioral therapy, mindfulness, music, exercise, partner support, empathy, meditation, and prayer. Studies demonstrate the role of the PFC during placebo analgesia, and in establishing links between pain and depression, anxiety, and loss of cognition. In particular, losses in PFC grey matter are often reversible after successful treatment of chronic pain.

Disease-modifying effects of natural Δ9-tetrahydrocannabinol in endometriosis-associated pain

“…Remarkably, the effects of THC were significantly different in endometriosis and sham mice (Figure 3c, 3d). Both aging and chronic pain are associated to local inflammatory events in these brain areas (Di Benedetto, Müller, Wenger, Düzel, & Pawelec, 2017; Ong, Stohler, & Herr, 2019). Our data suggest that these neuroinflammatory conditions modify the effects of THC on cognitive function, allowing to reveal an improvement of memory and inflammatory markers after chronic THC treatment.…”

Brain Resting-State Network Alterations Associated With Crohn's Disease

“…Although reduced GM volume of MPFC for CD as compared to HC has also been reported (23), this finding was not reproduced in the current study. The involvement of prefrontal cortex changes in CD may be explained by its role in mediating antinociceptive effects and modulation of pain (37). MPFC-nucleus accumbens connectivity has been linked to the chronification of pain (37).…”

“…The involvement of prefrontal cortex changes in CD may be explained by its role in mediating antinociceptive effects and modulation of pain (37). MPFC-nucleus accumbens connectivity has been linked to the chronification of pain (37). An investigation into pre-frontal cortex alterations and its associations with pain, psychiatric comorbidity, and cognitive deficits within CD is warranted.…”

Alcohol and Pain: A Translational Review of Preclinical and Clinical Findings to Inform Future Treatment Strategies

“…There is preliminary data that acamprosate may be more effective for individuals who engage in drinking primarily to relieve negative affect (Roos et al, ) and it is unclear whether acamprosate may also be more effective for individuals who are drinking to relieve negative affect mediated pain. Likewise, medications that are commonly used off‐label for the treatment of AUD (Kranzler and Soyka, ) including gabapentin, selective serotonin and norepinephrine reuptake inhibitors, and topiramate are commonly used in the treatment of a variety of pain conditions (Ong et al, ; Silberstein, ). To date, no randomized clinical trials have systematically studied pharmacotherapy options for individuals with comorbid AUD and chronic pain, and additional research is needed to test the efficacy of pharmacotherapy in this population.…”

“…Given the chronic and enduring nature of chronic pain, an acceptance‐based approach that improves functioning and is less concerned with pain relief may be particularly important for individuals who have a history of using alcohol for pain relief. Noninvasive brain stimulation approaches, including transcranial magnetic stimulation and transcranial direct current stimulation, may also be promising tools given evidence of effectiveness for the treatment of pain (Ong et al, ) and AUD (Stein et al, ). Finally, physical exercise may be beneficial for improving health outcomes and quality of life among both chronic pain patients (Geneen et al, ) and individuals with AUD (Hallgren et al, ).…”