Positive emotions and brain reward circuits in chronic pain

Abstract

Chronic pain is an important public health problem that negatively impacts quality of life of affected individuals and exacts enormous socio-economic costs. Chronic pain is often accompanied by comorbid emotional disorders including anxiety, depression and possibly anhedonia. The neural circuits underlying the intersection of pain and pleasure are not well understood. We summarize recent human and animal investigations demonstrating that aversive aspects of pain are encoded in brain regions overlapping with areas processing reward and motivation. We highlight findings revealing anatomical and functional alterations of reward/motivation circuits in chronic pain. Finally, we review supporting evidence for the concept that pain relief is rewarding and activates brain reward/motivation circuits. Adaptations in brain reward circuits may be fundamental to the pathology of chronic pain. Knowledge of brain reward processing in the context of pain could lead to the development of new therapeutics for the treatment of emotional aspects of pain and comorbid conditions.

Mu Opioid Receptors in Gamma-Aminobutyric Acidergic Forebrain Neurons Moderate Motivation for Heroin and Palatable Food

“…MORs are expressed throughout nociceptive pathways in the brain, spinal cord and sensory neurons (7) and our data are in accordance with previous studies indicating that major sites for these responses to morphine include periaqueductal gray (PAG) and spinal cord (47) where receptors are spared. Recent attention has focused on the implication of brain reward circuits in chronic pain (48) and a recent study used optogenetic manipulations to show that corticostriatal circuits regulate both nociceptive and affective aspects of neuropathic pain (49). Dlx-MOR mice responses to persistent pain will therefore be of interest in future investigations.…”

Enriched Environment and Effects on Neuropathic Pain: Experimental Findings and Mechanisms

“…On the contrary, VWR allows animals to exercise at their discretion in a more pleasant stress‐free environment. Studies have shown that VWR activates the mesolimbic reward pathway, resulting in pain relief . They suggest another putative reward mechanism governing the EE‐induced EIH in higher brain regions.…”

Mechanisms Underlying Bone and Joint Pain

“…amygdala) are implicated in processing the incoming signal and contribute to the perception of pain [29]. Notably, these different brain regions may contribute to different components of the complex sensation of pain that includes both sensory and emotional components [30, 31]. Clinical and preclinical studies are making important gains in our understanding of how these different brain regions contribute to the affective (unpleasant) and sensory (intensity, location) aspects of pain [32].…”