Atcherley, Christopher W.

Relief of aversive states, including pain, is rewarding and associated with an increase in dopamine (DA) release in the mesolimbic reward circuit. Measurement of DA in the nucleus accumbens (NAc) is usually accomplished with microdialysis but this method does not allow determination of the temporal relationship to pain, and to its relief. In this study, we used isoflurane anesthetized rats to measure NAc DA release on a millisecond to second timescale using fast scan cyclic voltammetry (FSCV). Our approach was to standardize the depth of anesthesia by a reflexive pain response to noxious heat, the tail‐flick test. The depth of anesthesia was standardized to this biological response of approximately 5.0 sec latency. FSCV involves the application of a specific triangular waveform at a high scan rate, allowing for oxidation and reduction of dopamine detected by a specialized electrode previously implanted in the NAc shell. Application of noxious heat to the tail was accompanied by a decrease in the DA signal that peaked at the time of the tail‐flick. Following the tail‐flick, there was a rebound increase in DA signal that peaked after 2.9 s. The data show a time‐locked DA response to pain onset, and to pain offset, likely related to the negative and positive components of pain and its relief. Support or Funding Information Supported by DA034975 from the NIH

ABSTRACTChronic pain is an important public health problem that negatively impacts the quality of life of affected individuals and exacts enormous socioeconomic 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 and demonstrate 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. J. Comp. Neurol. 524:1646–1652, 2016. © 2016 Wiley Periodicals, Inc.