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Open research questions in Pain Management and Placebo Effect

330 gap statements mined from Pain Management and Placebo Effect papers in our 7.9M-paper local library, which holds 1,261 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • The mechanisms of the placebo response are not well understood, although research indicates that expectation of an effect, preconceived bias, self-efficacy, co-interventions, and interaction with study staff may increase the incidence of placebo response.

    Predictive biomarkers of placebo response in patients with cancer: an exploratory analysis of the ABCD randomized clinical trial · 2026 · DOI

  • Finally, most of the studies (k = 6; n range: 46–93) were only sufficiently powered to detect moderate- to- large effects and thus were insufficiently powered to reliably detect weak effects.

    Trait responsiveness to verbal suggestions predicts nocebo responding: A meta‐analysis · 2024 · DOI

  • The review highlights that reassurance and behaviour support, while central to clinical care, remain variably theorised and insufficiently examined in relation to nocebo processes.

    The “Are You OK?” Paradox: A Scoping Review of Nocebo and Negative Suggestion in Healthcare Communication · 2026 · DOI

  • Whilst the placebo effect may ultimately represent a useful adjunct in perioperative pain management, current findings provide limited evidence in clinical populations.

    Updating UK clinical guidelines to incorporate the placebo effect in peri-operative care: challenges and opportunities · 2026 · DOI

  • Still, the literature mixes robust trial evidence with overstated claims about physiological effects, recovery, and digital applications, and a balanced synthesis for anesthesiologists is lacking.

    Hypnosis in Surgery: A Modern Adjunct to Anesthesia or a Forgotten Art? A Narrative Review · 2026 · DOI

  • Effects are heterogeneous, and virtual reality-delivered hypnosis has yielded inconsistent results.

    Hypnosis in Surgery: A Modern Adjunct to Anesthesia or a Forgotten Art? A Narrative Review · 2026 · DOI

  • The field of placebo effects shall remain uncertain because of the uncertainty of the mechanisms involved in the responses related to placebo.

    Placebo Effects: Neurological Mechanisms Inducing Physiological, Organic, and Belief Responses—A Prospective Analysis · 2024 · DOI

  • Future research should develop and test revised frameworks for control design in neurofeedback research. Future research should investigate the effects of non-contingent reinforcement in neurofeedback. Future research should explore the development of voluntary self-regulation in neurofeedback.

    Rethinking control conditions in clinical neurofeedback trials · 2026 · DOI

  • Future research should investigate the mechanisms underlying nocebo effects in long-term condition populations. Future research should evaluate the effectiveness of interventions aimed at reducing nocebo effects.

    Nocebo effects in long-term health conditions: a systematic review of experimental studies · 2026 · DOI

  • Experimental evidence on nocebo responses in long-term condition populations has not been systematically synthesised. There is a need to evaluate induction methods, symptom domains, and potential moderators to inform strategies for reducing avoidable nocebo-related harm.

    Nocebo effects in long-term health conditions: a systematic review of experimental studies · 2026 · DOI

  • The research highlights the need to explore the relationship between panic attacks and hypnotic processes.

    Is Panic Attack A Form of Negative Hypnosis · 2026 · DOI

  • There is a need for systematic investigation of the effects of open-label placebos on biomarkers. The literature lacks studies examining the effects of open-label placebos on hair cortisol concentrations and psychological distress.

    Open-label placebos reduce hair cortisol concentrations and psychological distress - a randomized controlled trial · 2026 · DOI

  • There is a need to evaluate the effectiveness of short-term psychotherapy in neurotic disorders. There is a lack of research on the application of short-term psychotherapy in clinical practice.

    Application of Short-Term Psychotherapy in Neurotic Disorders · 2026 · DOI

  • Although verbal suggestions are widely recognised as a hallmark method for inducing placebo responses, an open question is whether variability in placebo responding can be partly attributed to individual differences in trait responsiveness to verbal suggestions (REVS).

    Trait responsiveness to verbal suggestions predicts placebo responses: A multi-level meta-analysis · 2026 · DOI

  • The study suggests preliminary findings that warrant further investigation.

    Beyond pharmacological sedation: clinical hypnosis and self-hypnosis as patient-centred tools for perioperative anxiety management · 2026 · DOI

  • Future research on nocebo effects would benefit from the identification of which mechanisms apply in different contexts.

    Nocebo mechanisms in the social transmission of anxiety · 2026 · DOI

  • Prior neuroimaging studies have yielded heterogeneous findings, which may be reconciled from a connectomics perspective. The neural mechanisms of placebo analgesia are not well understood. There is a need for a novel approach to examine network localization of brain functional alterations related to placebo analgesia.

    Brain network representations of placebo analgesia · 2026 · DOI

  • The need for a comprehensive understanding of the neural mechanisms of hypnosis. The lack of a formal mechanistic model of hypnosis. The need for a clear definition of the concept of Fundamental Peace.

    Hypnosis as a Mechanism of Emotion Regulation and Self-Integration: An Integrative Review of Neural, Cognitive, and Experiential Pathways to Fundamental Peace · 2026 · DOI

  • The study was impacted by the coronavirus disease 2019 (COVID-19) pandemic, which limited opportunities for blood draws. The study had a limited sample size, with only 45 patients providing blood specimens. The study had to account for the potential confounding effects of the placebo response on the interpretation of the results.

    Predictive biomarkers of placebo response in patients with cancer: an exploratory analysis of the ABCD randomized clinical trial · 2026 · DOI

  • The study identifies the need to address the tension between transparency and potential harm in consent and risk communication. The review notes the challenge of exploring nocebo effects in paediatric and procedural healthcare contexts, where behaviour support and reassurance are central to practice.

    The “Are You OK?” Paradox: A Scoping Review of Nocebo and Negative Suggestion in Healthcare Communication · 2026 · DOI

  • Since placebo and nocebo-responses during acupuncture therapy are rarely studied in clinical contexts, the objective was to investigate placebo and nocebo-responses in a clinical context through comparing positive and negative side-effects between genuine and sham acupuncture, and to identify factors modifying placebo and nocebo-responses.

    Understanding Placebo and Nocebo Responses Based on a Randomized Sham-Controlled Study on Acupuncture in Integrative Cancer Care · 2024 · DOI

  • Investigate self-hypnosis protocols specifically designed to manage perioperative anxiety - Explore the use of audio-assisted self-hypnosis in larger, randomized…

    Beyond pharmacological sedation: clinical hypnosis and self-hypnosis as patient-centred tools for perioperative anxiety management · 2026 · DOI

  • The magnitude, durability, and generalizability of intervention effects remain highly variable across studies, - Direct comparisons across studies remain challenging, - The conditions under which interventions are most effective are still not fully understood, - Evidence for robust and long-lasting transfer to everyday cognitive functioning remains…

    Supporting Visual Working Memory in Healthy Aging: A Review of Current Interventions and Perspectives on Future Approaches · 2026 · DOI

  • Developing a structured, migraine-specific self-hypnosis training program - Refining the program to meet the needs of patients - Evaluating the program's effectiveness in reducing pain…

    Development and Refinement of HYlaMI, a Self-Hypnosis Training Program for Migraine Management: An ORBIT Phase Ia–Ib Acceptability Study · 2026 · DOI

  • Longitudinal assessment approaches that track changes in FP over time and in response to interventions, - Validation of the construct of Fundamental Peace, - Understanding individual differences in hypnotic…

    Hypnosis as a Mechanism of Emotion Regulation and Self-Integration: An Integrative Review of Neural, Cognitive, and Experiential Pathways to Fundamental Peace · 2026 · DOI

Most-cited papers in Pain Management and Placebo Effect

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Open questions raised by papers listed on this page include: (1) The literature mixes robust trial evidence with overstated claims about physiological effects, recovery, and digital applications, and a balanced synthesis for anesthesiologists is lacking (“Hypnosis in Surgery: A Modern Adjunct to Anesthesia or a Forgotten Art? A…”, 2026); (2) Future research should develop and test revised frameworks for control design in neurofeedback research (“Rethinking control conditions in clinical neurofeedback trials”, 2026); (3) Future research should investigate the mechanisms underlying nocebo effects in long-term condition populations (“Nocebo effects in long-term health conditions: a systematic review of…”, 2026); (4) There is a need for systematic investigation of the effects of open-label placebos on biomarkers (“Open-label placebos reduce hair cortisol concentrations and psychological…”, 2026); (5) There is a need to evaluate the effectiveness of short-term psychotherapy in neurotic disorders (“Application of Short-Term Psychotherapy in Neurotic Disorders”, 2026). 330 gap statements have been mined from Pain Management and Placebo Effect papers in our 7.9M-paper local library, which holds 1,261 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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