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

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.