Pain is a fundamental experience that promotes survival. In humans, pain stands at the intersection of multiple health crises: chronic pain, the opioid epidemic, and health disparities. The study of placebo analgesia highlights how social, cognitive, and affective processes can directly shape pain, and identifies potential paths for mitigating these crises. This review examines recent progress in the study of placebo analgesia through affective science. It focuses on how placebo effects are shaped by expectations, affect, and the social context surrounding treatment, and discusses neurobiological mechanisms of placebo, highlighting unanswered questions and implications for health. Collaborations between clinicians and social and affective scientists can address outstanding questions and leverage placebo to reduce pain and improve human health.Pain: a biopsychosocial phenomenon that requires integrative research Pain (see Glossary) lies at the core of multiple health crises. It is central to the opioid epidemic [1,2], there are substantial health disparities in pain [3][4][5], over 11% of American adults report experiencing daily pain [6], and chronic pain is highly comorbid with other central nervous system conditions, including mental health illnesses [7] and substance use disorders [8]. Healthcare practitioners have reduced opioid prescriptions in response to the opioid epidemic [9], but we lack effective alternatives, including nonaddictive and nonpharmacological therapies.Hope can be found in the progress the field has made in isolating the mechanisms that contribute to pain through animal models because the systems that process pain [10] and nociception are highly conserved across species. Nevertheless, pain in humans is ultimately a subjective, conscious experience that involves the integration of sensory processing, emotion, context, and decision making. Understanding human pain requires an integrative approach that draws on psychology, neuroscience, and medicine. In this review I focus on placebo analgesia, a phenomenon that lies at the intersection of these diverse fields. In the following sections I review the critical influences of expectations, affect, and the social context surrounding treatment (Figure 1, Key figure). I then discuss the brain mechanisms underlying placebo effects and the extent to which placebo analgesia provides insights into domains other than pain. Throughout, I emphasize that research on the placebo effect has important implications for the urgent crises surrounding opioid use disorder and health disparities in pain.
HighlightsThe study of placebo analgesia provides insights into how pain and clinical outcomes are shaped by social, cognitive, and affective processes.