Mesolimbic dopamine signaling in acute and chronic pain: implications for motivation, analgesia, and addiction

The mesolimbic dopamine system comprises neurons in the ventral tegmental area (VTA) andsubstantia nigra (SN), projecting to the ventral striatum. This system was originally described to mediate pleasure and goal-directed movement associated with rewarding stimuli. However, it is now clear that dopamine, although crucial for reward processing, drives not the hedonic experience of reward (“liking”) but rather the instrumental behavior of reward-driven actions (“wanting”). Phasic dopamine acts as an incentive salience signal underlying reinforcement learning. Moreover, aversive stimuli, such as pain, also stimulate dopamine, further diminishing the idea of dopamine as a “reward” signal. Recent studies suggest that dopamine neurons in the VTA and SN form a heterogeneous population tuned to either (or both) aversive or rewarding stimuli. This review will summarize our current understanding of the role of the mesolimbic dopamine system in acute pain and the changes that occur in chronic pain.