Neural mechanisms of endogenous pain control (360G-Wellcome-214251_Z_18_Z)

Pain plays a vital role in self-protection and injury avoidance, and my research to date has outlined a core learning and decision-making framework, based on reinforcement learning theory, that shows how this is achieved in the brain. Recently, I have shown that this controls not only actions, but also the intensity of perceived pain itself (endogenous pain control) - an effect related to predicted uncertainty. This leads to the underlying hypothesis that pain is actively tuned by the value of its information - a precise metric that derives from an estimate of the extra benefit to survival achieved through learning. This leads to a series of testable questions: i) how and where is this information computed, ii) is it opioid-dependent, iii) how is it maintained over time, iv) how and at what level does it control pain representations, v) and can it be targeted to reduce pain. The proposed research describes the series of behavioural and neuroimaging experiments that will answer these questions, aiming to provide a comprehensive circuit level account of the major endogenous pain control process in the brain. Ultimately, the results aim to provide a basis for developing precision interventions for chronic pain.