Activision of Reward Pathway by Pain Relief

Abstract

Recent progress in the pain research field has shed light on the role of dopaminergic neurotransmission in pain perception. However, the relationship between pain relief and reward, and how pain relief modulates the reward circuitry is not well understood. Previous conditioned place preference studies (CPP) in our laboratory have demonstrated that pain relief is rewarding and established the essential role of the ventral tegmentum area (VTA) in the reward that results from pain relief. Based on these observations, we hypothesized that pain relief will activate neurons in the reward pathway. Using immunohistochemical studies, we investigated changes in cFos-staining, a marker for neural activation, in tyrosine hydroxylase-labeled dopaminergic neurons in the VTA. We found that peripheral nerve block selectively increased staining for cFos in the VTA in rats with hind paw incision pain, indicating activation of reward circuitry upon pain relief. Additionally, many of these c-Fos positive cells in the VTA were also tyrosine hydroxylase (TH) positive, suggesting that these were dopaminergic neurons that may underlie the reward associated with pain relief.