White matter integrity of the descending pain modulatory system is associated with interindividual differences in placebo analgesia

The ability for endogenous pain control varies considerably among individuals. The mechanisms underlying this interindividual difference are incompletely understood. We used placebo analgesia as a classic model of endogenous pain modulation in combination with diffusion tensor magnetic resonance imaging to test the hypothesis of a structural predisposition for the individual capacity of endogenous pain control. Specifically we determined white matter integrity within and between regions of the descending pain modulatory system. Twenty-four healthy participants completed a placebo paradigm and underwent diffusion tensor magnetic resonance imaging. The individual placebo analgesic effect was correlated with white matter integrity indexed by fractional anisotropy. The individual placebo analgesic effect was positively correlated with FA in the right dorsolateral prefrontal cortex, left rostral anterior cingulate cortex, and the periaqueductal grey. Probabilistic tractography seeded in these regions showed that stronger placebo analgesic responses were associated with increased mean fractional anisotropy values within white matter tracts connecting the periaqueductal grey with pain control regions such as the rostral anterior cingulate cortex and the dorsolateral prefrontal cortex. Our findings provide the first evidence that the white matter integrity within and between regions of the descending pain modulatory network is critically linked with the individual ability for endogenous pain control.