A social affective neuroscience lens on placebo analgesia

Abstract

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.

What Do Placebo and Nocebo Effects Have to Do With Health Equity? The Hidden Toll of Nocebo Effects on Racial and Ethnic Minority Patients in Clinical Care

“…Further research has shown that Black patients receive less information than White patients, ask fewer questions, and are less likely to participate in decision making when experiencing lower-quality communication ( Shen et al, 2018 ). Healthcare professionals have also been shown to hold false beliefs about biological differences between White and Black patients that correlate with their treatment decisions ( Hoffman et al, 2016 ; Atlas, 2021 ). A study assessing whether patient factors affected physicians’ underestimation of patient pain found that physicians are twice as likely to underestimate pain in Black patients ( Staton et al, 2007 ).…”

“…In laboratory-based studies, subjects are exposed to an aversive stimulus (e.g., heat pain or electric shock) and then given an inert treatment (e.g., a saline infusion or inert cream) with the instruction to expect alleviation (i.e., “this will reduce your pain”) or worsening of the pain (i.e., “this will increase your pain”). Association between treatment and its effect can also be induced by conditioning through repeated pairing of a painful stimulus and a treatment to guide the experience of pain ( Atlas, 2021 ).…”

“…The mechanism underlying the placebo response has captivated and bewildered clinicians and researchers for decades. To understand why patients respond to seemingly inert treatments, placebo researchers investigated components of the clinician-patient encounter and found that positive expectations , both conscious and unconscious, are key drivers of placebo effects ( Atlas, 2021 ). The word “placebo” is derived from the Latin placere , “to please.” While placebo effects are widely known to be salubrious, their opposite, nocebo effects, are not as well known.…”

“…The patient repeatedly feels nauseous during chemotherapy, and over time they are conditioned to associate the treatment room with nausea, even if the room itself is not causing the symptom. Patients that had negative experiences or experienced discrimination in the clinical encounter have different expectations, including increased mistrust and expectations of experiencing discrimination again in the future, than those that have had mostly positive experiences in the clinical encounter ( Atlas, 2021 ; Hall et al, 2021 ). The implication is that patients could be conditioned to anticipate future poor outcomes with negative encounters.…”

Great Expectations: Recommendations for improving the methodological rigor of psychedelic clinical trials

“…Outcome expectancies also have strong effects relative to the active effects of psychotropic drugs (Rutherford and Roose 2013). In trials where subjective measures are the primary basis for outcome, outcome expectancies may particularly moderate therapeutic outcomes (Atlas 2021). Fillingim and Price (2005) concluded that, in placebo analgesia studies for example, outcome expectancies accounted for up to 81% of variance in post-treatment pain ratings.…”