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Open research questions in Pain Management and Placebo Effect

312 unresolved questions extracted from the limitations and future-work sections of 925 Pain Management and Placebo Effect papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • identification of which mechanisms apply in different contexts, - empirical validation of the social transmission of anxiety via the nocebo effect, - investigation of nocebo education as a means to mitigate the impact of the nocebo effect

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

  • The paper identifies a gap in understanding the mechanisms of the nocebo effect. The breadth of the nocebo construct invites its application to a wide range of expectation-induced processes. 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

  • No standard diagnostic approach exists to identify nocebo effects in clinical practice. Prior work has focused on experimental research, with limited translation to real-world clinical settings. There is a need for a novel provocation protocol to address this gap.

    A novel provocation protocol to identify nocebo effects in clinical practice—a proof-of-concept n-of-1 study · 2026 · DOI

  • Investigate the long-term effects of the intervention. Examine the effectiveness of the intervention in different populations, such as children or older adults. Explore the potential benefits of combining digital hypnotherapy with other sensory modalities, such as music or nature sounds.

    Promoting relaxation through essential oil-enhanced digital hypnotherapy: A randomized controlled trial · 2026 · DOI

  • Future studies could investigate the effects of PA on other types of pain, - Future research could explore the relationship between PA and other psychological processes, - Future studies could use the FCNM approach to examine the neural mechanisms of other placebo effects

    Brain network representations of placebo analgesia · 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

  • There is a lack of validated approaches to avoid the potential harms of mental health awareness efforts without reducing awareness efforts. Current approaches to mental health awareness may cause unnecessary self-diagnosis and worsening symptoms. There is a need for a brief and simple to administer intervention that can be scalable and easy to implement in many settings.

    Inform and do no harm: Nocebo education reduces false self-diagnosis caused by mental health awareness · 2025 · DOI

  • Considerable overlap of primary studies across the included systematic reviews, - Only nine meta-analyses were rated to have high methodological quality, - The diversity of populations, comparators, and outcomes limited the synthesis of results

    Meta-analytic evidence on the efficacy of hypnosis for mental and somatic health issues: a 20-year perspective · 2024 · DOI

  • There is a need for a comprehensive overview of meta-analyses examining the efficacy of hypnosis for mental and somatic health issues. There is a lack of understanding of the safety of hypnosis interventions. There is a need to identify gaps in the current research literature.

    Meta-analytic evidence on the efficacy of hypnosis for mental and somatic health issues: a 20-year perspective · 2024 · DOI

  • Few digital interventions for promoting relaxation combine multiple sensory modalities. There is a lack of studies evaluating the effectiveness of digitally guided hypnotherapy interventions with physical olfactory cues. The potential of aromatherapy to induce a conditioned relaxation effect is not well understood.

    Promoting relaxation through essential oil-enhanced digital hypnotherapy: A randomized controlled trial · 2026 · DOI

  • Further research is needed to establish the diagnostic accuracy and generalizability of the protocol - The protocol could be applied to other substances and patient populations to explore its potential - Research could investigate the frequency of nocebo effects in clinical practice

    A novel provocation protocol to identify nocebo effects in clinical practice—a proof-of-concept n-of-1 study · 2026 · DOI

  • However, their impact on food metabolism and food-related behaviors remains underexplored.

    Expectation shapes hunger and craving: placebo effects of verbal suggestion on food-related experiences · 2026 · DOI

  • Background/Objectives: Migraine is a prevalent and disabling neurological condition for which complementary non-pharmacological interventions remain underexplored.

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

  • While animal models are increasingly used to explore the underlying mechanisms of these phenomena, it remains unclear whether animals experience placebo and nocebo effects in a manner comparable to humans or whether the associated neurobiological pathways are conserved across species.

    Direct comparisons of neural activity during placebo analgesia and nocebo hyperalgesia between humans and rats · 2025 · DOI

  • To advance our understanding, future research should explore these attentional mechanisms, in conjunction with neurophysiological correlates.

    The Role of Attention in Placebo and Nocebo Effects · 2024 · DOI

  • Treatment options for preoperative anxiety are often limited as sedatives cause side effects and their efficacy remains controversial.

    Preoperative Anxiolysis and Treatment Expectation (PATE Trial): open-label placebo treatment to reduce preoperative anxiety in female patients undergoing gynecological laparoscopic surgery – study protocol for a bicentric, prospective, randomized-controlled trial · 2024 · DOI

  • The use of OLPs to reduce preoperative anxiety and modify clinically relevant postoperative outcomes has not yet been investigated.

    Preoperative Anxiolysis and Treatment Expectation (PATE Trial): open-label placebo treatment to reduce preoperative anxiety in female patients undergoing gynecological laparoscopic surgery – study protocol for a bicentric, prospective, randomized-controlled trial · 2024 · DOI

  • Open-label (honestly prescribed) placebos (OLPs) may relieve CBP without deception, but OLP mechanisms remain poorly understood.

    Open-Label Placebo Injection for Chronic Back Pain With Functional Neuroimaging · 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

  • The standard placebo-controlled model is conceptually mismatched to an active and interactive technique such as neurofeedback. There is a need for a revised framework for control design in neurofeedback research.

    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 study identifies a gap in understanding the cognitive mechanisms that underlie panic attacks. 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

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312 open questions have been extracted from the limitations and future-work passages of 925 Pain Management and Placebo Effect papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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