Placebo Pain Relief: Mechanisms and Therapeutic Opportunities

The placebo effect has accompanied medicine throughout its history and remains a powerful modulator of health and disease. While the rise of double-blind, randomized, placebo-controlled trials has positioned placebo effects primarily as methodological controls, accumulating evidence has prompted a reassessment of their underlying mechanisms and therapeutic value. Over the past several decades, substantial progress has been made in elucidating the psychological, neural circuit, and molecular bases of placebo effects. In this review, we summarize recent clinical and preclinical findings that reveal how cognitive processes engage endogenous pain-modulatory circuits to shape pain perception. We further discuss strategies for leveraging placebo-related mechanisms in current clinical practice and outline potential future directions in which a more precise mechanistic understanding may enable targeted, ethical, and effective approaches to pain management.