Can placebo and nocebo effects generalize within pain modalities and across somatosensory sensations?

Weng, Lingling; Peerdeman, Kaya J.; Porta, Delia Della; Laarhoven, Antoinette I. M. van; Evers, Andrea

doi:10.1097/j.pain.0000000000002390

Cited by 15 publications

(24 citation statements)

References 44 publications

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“…Neural mechanisms that support these psychological processes may be similar across clinical outcomes, although downstream mediators of placebo effects are likely to differ across conditions. Although few studies have compared placebo effects across modalities [42,[64][65][66][67], a larger literature focuses on whether the brain mechanisms that process pain (and show reductions with placebo) are unique to pain. In the following section I review brain mechanisms of placebo analgesia and evaluate evidence regarding pain specificity.…”

Section: Brain Mechanisms Of Placebo Analgesia and Specificity To Painmentioning

confidence: 99%

A social affective neuroscience lens on placebo analgesia

Atlas

2021

Trends in Cognitive Sciences

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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.

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Section: Brain Mechanisms Of Placebo Analgesia and Specificity To Painmentioning

confidence: 99%

A social affective neuroscience lens on placebo analgesia

Atlas

2021

Trends in Cognitive Sciences

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“…Second, as this nocebo itch study consisted of only a single session, further study could investigate how long the induction and (response) generalization of nocebo effects persist. Third, although the findings suggested some links between the induction of nocebo effects and their generalization, it remains unclear whether nocebo responders are more prone to generalization effects than non‐responders 16 . Exploring the role of responders' characteristics in generalization of nocebo effects will help in individually predicting the prevalence of nocebo effects.…”

Section: Discussionmentioning

confidence: 99%

“…This is called response generalization, where a generalization response is alike the previous response (eg nocebo hyperknesis) to a stimulus, upon exposure to a cue (eg nocebo solution) 17 . For instance, indirect evidence showed that nocebo effects generalize from electrically evoked itch to histamine‐evoked itch 15,16 . Theoretically, generalization effects are stronger when the outcomes are more similar 18 .…”

Section: Introductionmentioning

confidence: 99%

“…Previously induced nocebo effects on one sensation can affect other sensations evoked by other, similar stimuli. 15 , 16 This is called response generalization, where a generalization response is alike the previous response (eg nocebo hyperknesis) to a stimulus, upon exposure to a cue (eg nocebo solution). 17 For instance, indirect evidence showed that nocebo effects generalize from electrically evoked itch to histamine‐evoked itch.…”

Section: Introductionmentioning

confidence: 99%

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Induction and generalization of nocebo effects on itch

Weng

Laarhoven

Peerdeman

et al. 2022

Experimental Dermatology

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Nocebo effects, that is, negative treatment outcomes due to negative expectancies, can increase itch. Moreover, indirect evidence has shown that nocebo hyperknesis can generalize to another itch modality. Knowledge on response generalization can help to prevent and decrease negative effects. The aims of this study were to investigate (1) the efficacy of inducing nocebo effects on cowhage‐evoked itch via verbal suggestions and (2) whether these effects can generalize to (2a) mechanically evoked touch and (2b) mechanically evoked itch. Forty‐four healthy participants watched a video suggesting that a nocebo solution increases cowhage‐evoked itch and that a control solution does not affect itch. Subsequently, cowhage, mechanical itch, and mechanical touch stimuli were applied. Nocebo effects were measured as the difference in both mean and peak of the outcomes itch and urge to scratch between nocebo and control trials. Main analyses revealed significant nocebo effects on mean and peak itch for all stimuli. For urge to scratch, a significant nocebo effect was only observed for mechanical touch (peak). As mechanical stimuli did not induce pure sensations as planned, posthoc sensitivity analyses were run for mechanical stimuli that individually induced either touch or itch at baseline. These analyses showed similar results for generalization to mechanical itch, but generalization to mechanical touch was non‐significant. This study showed that merely verbal suggestion can induce nocebo effects on cowhage‐evoked itch and that these effects can generalize to another itch modality. Future studies may examine how to prevent negative experiences from generalizing to subsequent encounters.

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“…Pain may be nociceptive, neuropathic or mixed ( Angst et al, 2020 ). There is evidence that the cytokine profile in COVID-19 contributes to the promotion of pain and also improves pain states ( McFarland et al, 2021 ; Weng et al, 2021 ), and that SARS-CoV-2 infection may worsen neural damage or neural pain in leprosy patients.…”

Section: Introductionmentioning

confidence: 99%

Kynurenines in the Pathogenesis of Peripheral Neuropathy During Leprosy and COVID-19

Oliveira

Athaide

RAHMAN

et al. 2022

Front. Cell. Infect. Microbiol.

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Inflammatory disorders are associated with the activation of tryptophan (TRYP) catabolism via the kynurenine pathway (KP). Several reports have demonstrated the role of KP in the immunopathophysiology of both leprosy and coronavirus disease 19 (COVID-19). The nervous system can be affected in infections caused by both Mycobacterium leprae and SARS-CoV-2, but the mechanisms involved in the peripheral neural damage induced by these infectious agents are not fully understood. In recent years KP has received greater attention due the importance of kynurenine metabolites in infectious diseases, immune dysfunction and nervous system disorders. In this review, we discuss how modulation of the KP may aid in controlling the damage to peripheral nerves and the effects of KP activation on neural damage during leprosy or COVID-19 individually and we speculate its role during co-infection.

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Can placebo and nocebo effects generalize within pain modalities and across somatosensory sensations?

Abstract: Supplemental Digital Content is Available in the Text.Placebo and nocebo effects induced by verbal suggestion and conditioning can generalize across pain modalities, but generalization to itch does not necessarily take place.

Cited by 15 publications

References 44 publications

A social affective neuroscience lens on placebo analgesia

A social affective neuroscience lens on placebo analgesia

Induction and generalization of nocebo effects on itch

Kynurenines in the Pathogenesis of Peripheral Neuropathy During Leprosy and COVID-19

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