Association between Chronic Pain and Alterations in the Mesolimbic Dopaminergic System

Abstract

Chronic pain (pain lasting for >3 months) decreases patient quality of life and even occupational abilities. It can be controlled by treatment, but often persists even after management. To properly control pain, its underlying mechanisms must be determined. This review outlines the role of the mesolimbic dopaminergic system in chronic pain. The mesolimbic system, a neural circuit, delivers dopamine from the ventral tegmental area to neural structures such as the nucleus accumbens, prefrontal cortex, anterior cingulate cortex, and amygdala. It controls executive, affective, and motivational functions. Chronic pain patients suffer from low dopamine production and delivery in this system. The volumes of structures constituting the mesolimbic system are known to be decreased in such patients. Studies on administration of dopaminergic drugs to control chronic pain, with a focus on increasing low dopamine levels in the mesolimbic system, show that it is effective in patients with Parkinson’s disease, restless legs syndrome, fibromyalgia, dry mouth syndrome, lumbar radicular pain, and chronic back pain. However, very few studies have confirmed these effects, and dopaminergic drugs are not commonly used to treat the various diseases causing chronic pain. Thus, further studies are required to determine the effectiveness of such treatment for chronic pain.

Electroacupuncture Ameliorates Chronic Inflammatory Pain-Related Anxiety by Activating PV Interneurons in the Anterior Cingulate Cortex

“…Activity of ACC neurons is necessary and sufficient for the coding and processing of pain and the accompanying emotional pain, and the balance between neural excitation and inhibition is necessary for the normal function of the ACC ( Gong et al, 2010 ; Zugaib et al, 2014 ). In chronic pain clinical practice and basic research, changes in neurotransmitters in the central system have been found, which was caused by the dysregulation of GABAergic, glutamatergic, dopaminergic and opioidergic mechanisms ( Mhalla et al, 2010 ; Bannister and Dickenson, 2020 ; Yang et al, 2020 ). Dysfunction of GABAergic interneurons, as a major inhibitory system in the central nervous system, was reported to be closely related to the pathogenesis of anxiety-like behavior and chronic pain ( Möhler, 2012 ; Lau and Vaughan, 2014 ).…”

Clostridioides difficileinfection increases circulating p-cresol levels and dysregulates brain dopamine metabolism: linking gut-brain axis to autism spectrum disorders?

“…Generally, DA is considered as anti-nociceptive and persistent pain is often associated with a decreased DA levels in brain as opposed to acute pain, such as a pin prick. [55][56][57][58] Therefore, a significantly increased DA and its degradation products observed in the striatum and pre-frontal cortex could be potentially attributed to a pathway that directly alters DA metabolism, such as p-cresol mediated inhibition of DBH. Increased DA (or its degradation products) to norepinephrine ratio as seen in both striatum and pre-frontal cortex of the C. difficile infected mice has been implicated in disorders of DBH activity, such as low DBH levels due to mutations in DBH coding genes.…”

Pain-Related Abnormal Neuronal Synchronization of the Nucleus Accumbens in Parkinson’s Disease

“…Several pathways involved in sensory processing modulate pain [ 5 ]. These pathways are altered across the “on” and “off” states in PD, and an alteration of the pathways is closely related to pain processing in the brain [ 6 , 7 , 8 ].…”

“…These pathways are altered across the “on” and “off” states in PD, and an alteration of the pathways is closely related to pain processing in the brain [ 6 , 7 , 8 ]. The mesolimbic pathway is associated with reward and motivation and plays an important role in the perception and modulation of pain [ 5 ]. The nucleus accumbens (NAc) is a central component of the mesolimbic pathway and is connected to pain-related brain regions [ 5 ].…”