Effects of pharmacological manipulations on endogenous perceptual modulation
pain
Both dopamine and opioids are implicated in relief processing, although their precise roles remain unclear. We found endogenous relief modulation here was modulated by enhanced dopamine availability induced by the intake of levodopa. Importantly, all three core aspects of informational-sensitivity were modulated by levodopa: active controllability, unpredictability, and association with novelty seeking. These findings also illustrate potential parallels with the previous observation of endogenous pain inhibition by extrinsic monetary reward co-occurring with experimental pain (The role of dopamine in pain relief in the context of reinforcement is supported by findings of increased dopamine release induced by pain relief in the Nucleus accumbens of rats (In contrast to our hypothesis, pharmacologically blocking opioid receptors using naltrexone did not reduce modulation endogenous pain inhibition in this task. The doses and methods used here are comparable to those used in other contexts which have identified opioidergic effects. Using positron emission tomography In humans, Although we did not assess the affective component of the relief experience, we implemented two outcome measures that are assumed to capture independent aspects of the pain experience: VAS ratings indicate perception of phasic changes (outcomes), while the behavioral measure indicates perceptual within-trial sensitization or habituation in response to the tonic stimulation within each trial. We found enhanced endogenous modulation by controllability and unpredictability in VAS ratings, in line with the view that endogenous modulation enhances behaviorally relevant information. In contrast, the within-trial sensitization did not differ between the active and passive conditions under placebo. In a previous study using a similar experimental paradigm 