Brain Circuits Encoding Reward from Pain Relief

Relief from pain in humans is rewarding and pleasurable. Primary rewards, or reward-predictive cues, are encoded in brain reward/motivational circuits. While considerable advances have been made in our understanding of reward circuits underlying positive reinforcement, less is known about the circuits underlying the hedonic and reinforcing actions of pain relief. We review findings from electrophysiological, neuroimaging, and behavioral studies supporting the concept that the rewarding effect of pain relief requires opioid signaling in the anterior cingulate cortex (ACC), activation of midbrain dopamine neurons, and the release of dopamine in the nucleus accumbens (NAc). Understanding of circuits that govern the reward of pain relief may allow the discovery of more effective and satisfying therapies for patients with acute or chronic pain.

TrendsElectrophysiological studies in rats demonstrate that a subset of mesolimbic dopamine neurons that are initially inhibited by a noxious stimulation show ‘rebound’ excitation at the offset of the stimulus.Recent investigations using fast-scan cyclic voltammetry in rats show phasic dopamine release in the nucleus accumbens shell at the termination of a noxious tail pinch.Using neuroimaging in humans and rats, increased BOLD activity was detected at the offset of a brief noxious stimulus in the nucleus accumbens and in the anterior cingulate cortex.In Drosophila, rodents, and humans, relief of an acute painful stimulus is associated with conditioned reward learning.In rats, relief of ongoing pain promotes a conditioned place preference that requires opioid signaling in the anterior cingulate cortex and subsequent release of dopamine in the nucleus accumbens.