Placebo and nocebo effects are positive and negative treatment-like effects, respectively, that cannot be attributed to an active treatment component. They are caused by patients’ expectations of...Show morePlacebo and nocebo effects are positive and negative treatment-like effects, respectively, that cannot be attributed to an active treatment component. They are caused by patients’ expectations of symptom improvement or worsening. Both effects play a significant role in the treatment of itch. However, there is a great variability in their extent in healthy individuals and patient groups, which may be partly explained by genetic variants in specific neurotransmitter pathways. This study is the first to investigate genetic predictors of placebo and nocebo effects on itch. Based on research in pain, the genes COMT rs4680, FAAH rs324420, and OPRM1 rs1799971 were identified to investigate their potential role in the extent to which placebo and nocebo effects on itch were induced in healthy individuals. This cross-trial analysis included 58 in the placebo and 127 healthy genotyped participants in the nocebo analysis from three studies. Itch stimuli were elicited electrically or with histamine, and placebo and nocebo effects were induced with specific learning processes, i.e., conditioning with verbal suggestion, or antihistamine was classically conditioned. COMT met/met variants demonstrated significantly higher placebo effects on itch compared to val/val variants, 95% BCa CI [0.026, 1.263]. No other significant differences were found between the variants of COMT, FAAH and OPRM1 and placebo or nocebo effects on itch. Knowledge on genetic predictors of placebo and nocebo effects on itch could help to improve clinical trial design and allow clinicians to tailor itch-reducing treatments such that they optimize treatment efficacy. Future research should focus on a replication study with a larger cohort and homogenous itch-inducing methods as well as learning processes to verify the studied relationship.Show less
