Modulation of pain, nociception, and analgesia by the brain reward center

Abstract

The midbrain dopamine center comprises a key network for reward, salience, motivation, and mood. Evidence from various clinical and preclinical settings points to the midbrain dopamine circuit as an important modulator of pain perception and pain-induced anxiety and depression. This review summarizes recent findings that shed light to the neuroanatomical, electrophysiological and molecular adaptations that chronic pain conditions promote in the mesolimbic dopamine system. Chronic pain states induce changes in neuronal plasticity and functional connectivity in several parts of the brain reward center, including nucleus accumbens, the ventral tegmental area and the prefrontal cortex. Here, we discuss recent findings on the mechanisms involved in the perception of chronic pain, in pain-induced anxiety and depression, as well as in pain-killer addiction vulnerability. Several new studies also show that the mesolimbic dopamine circuit potently modulates responsiveness to opioids and antidepressants used for the treatment of chronic pain. We discuss recent data supporting a role of the brain reward pathway in treatment efficacy and we summarize novel findings on intracellular adaptations in the brain reward circuit under chronic pain states.

Neurobiological Correlates of Pain Avoidance-Like Behavior in Morphine-Dependent and Non-Dependent Rats

“…This reward tolerance could actually lead to an escalation of opioid use, as animals experiencing chronic inflammatory pain prefer to self-administer higher levels of opioids (Hipólito et al, 2015). Our results are consistent with the theory that alterations of reward brain systems (e.g., TH activation) may contribute to the emergence of negative affective pain states (Mitsi and Zachariou, 2016). In future studies, we plan to directly measure alterations in dopamine levels and dopamine receptor signaling in the DS vs. VS during the mechanical conflict-avoidance task.…”

Etiology and Pharmacology of Neuropathic Pain

“…This may relate to the changes in affect (anxiety, depression) experienced by neuropathic pain patients (Mitsi and Zachariou, 2016). It was also shown recently that peripheral nerve injury selectively increases excitability of the nucleus accumbens indirect pathway spiny projection neurons and alters their synaptic connectivity.…”

Love as a Modulator of Pain

“…The dopamine brain reward centre is involved in mood and motivation (63) and includes the ventral tegmental area. Neurons in the ventral tegmental area also project to the nucleus accumbens and prefrontal cortex (64). The OFC is another area that is notably associated with pleasure functioning (63).…”

“…The mesolimbic dopamine circuit modulates responsiveness to the opioids and antidepressants used in chronic pain treatment (64). In addition, aberrant functioning of the circuit has been linked to the development of chronic pain states (65,66).…”