Genetic Influences on Neural Responses in Placebo Analgesia Circuitry

Placebo analgesia is a well-established medical phenomenon with overlapping neural representations between humans and rodents, but the genetic contribution to this conserved neural circuitry remains unknown. Using functional brain imaging in 305 monozygotic and dizygotic twins, we quantified the heritability of neural activation in placebo analgesia brain circuity during evoked pain, including the rostral anterior cingulate cortex, brainstem and cerebellum, using the ACE model. Neural responses showed significant heritability, with additive genetics accounting for 21 to 49% of the variance (A = 0.21-0.49), indicating that genetics have a moderate effect on pain-evoked brain activity within the placebo analgesia circuitry. For the first time, our findings reveal a heritable component of the neural network supporting placebo analgesia. By linking genetic variations to neural responses in placebo analgesia circuitry, this study bridges human and preclinical research and opens new ways for improving clinical trial methodology and tailoring pain therapies to individual genetic profiles.