The importance of context: When relative relief renders pain pleasant

Siri Leknes, Chantal Berna, Michael C. Lee, Gregory D. Snyder, Guido Biele, Irene Tracey

Context can influence the experience of any event. For instance, the thought that "it could be worse" can improve feelings towards a present misfortune. In this study we measured hedonic feelings, skin conductance, and brain activation patterns in 16 healthy volunteers who experienced moderate pain in two different contexts. In the "relative relief context," moderate pain represented the best outcome, since the alternative outcome was intense pain. However, in the control context, moderate pain represented the worst outcome and elicited negative hedonic feelings. The context manipulation resulted in a "hedonic flip," such that moderate pain elicited positive hedonics in the relative relief context. Somewhat surprisingly, moderate pain was even rated as pleasant in this context, despite being reported as painful in the control context. This "hedonic flip" was corroborated by physiological and functional neuroimaging data. When moderate pain was perceived as pleasant, skin conductance and activity in insula and dorsal anterior cingulate were significantly attenuated relative to the control moderate stimulus. "Pleasant pain" also increased activity in reward and valuation circuitry, including the medial orbitofrontal and ventromedial prefrontal cortices. Furthermore, the change in outcome hedonics correlated with activity in the periacqueductal grey (PAG) of the descending pain modulatory system (DPMS). The context manipulation also significantly increased functional connectivity between reward circuitry and the PAG, consistent with a functional change of the DPMS due to the altered motivational state. The findings of this study point to a role for brainstem and reward circuitry in a context-induced "hedonic flip" of pain.