The search for placebo biosignatures in chronic cough: looking through the lens of neurobiology

Extract Placebo effects have long fascinated clinicians and scientists, not only as a methodological nuisance in clinical trials, but also as a window into potentially powerful endogenous regulatory systems. While in respiratory medicine the placebo phenomenon has often been considered less central than in pain or psychiatric disorders, recent pivotal randomised clinical trials for chronic cough, particularly with P2X purinoceptor 3 antagonists such as gefapixant, have drawn renewed attention to placebo responses [1]. These studies demonstrated unexpectedly large placebo responses, influencing not only subjective outcomes but also objective cough frequency measures [2]. This raises fundamental questions: how can placebo so strongly modulate reflexive motor behaviour? What neural systems mediate these effects? And how might they be harnessed for better trial design and patient care?