Placebo and Pain

Preface

Contributors

Chapter 1. Historical Aspects of Placebo Analgesia

Abstract

Introduction

Definitions and Conceptualization

Placebos as Controls

Placebos as a Treatment

Placebo in the Early 20th Century

Placebo as More Than Just an Experimental Control

The Emergence of the Study of Placebo Mechanisms

Using History to Further Explore Placebo Analgesia

References

Chapter 2. Neurochemistry of Placebo Analgesia: Opioids, Cannabinoids and Cholecystokinin

Abstract

Introduction

Some Types of Placebo Analgesia are Mediated by Endogenous Opioids

Endocannabinoids are Involved in Some Types of Placebo Analgesia

Nocebo Hyperalgesia is Mediated by Cholecystokinin

Conclusions

References

Chapter 3. Placebo Analgesia in Rodents

Abstract

Acknowledgments

Introduction

The Placebo Effect in Animals

Studying Placebo Analgesia in Animal Models

Dissection of Placebo Analgesia in Mice

Placebo Analgesia Affects the Behavioral Despair Tests in Mice

The Opioid Receptors Involved in the Placebo Response in Rats

The Pros and Cons of Studying Placebo in the Animal Model

Conclusion and Future Directions

References

Chapter 4. Molecular Mechanisms of Placebo Responses in Humans

Abstract

Acknowledgments

Introduction

Placebo-Induced Activation of Regional Endogenous Opioid Neurotransmission

Dopaminergic Mechanisms in the Formation of Placebo Analgesic Effects

Theories of Placebo Analgesia and Placebo-Induced Activation of Regional Endogenous Opioid Neurotransmission

Personality Predictors of Placebo-Induced Activation of Regional Endogenous Opioid Neurotransmission

Conclusions

References

Chapter 5. How does EEG Contribute to Our Understanding of the Placebo Response?: Insights from the Perspective of Bayesian Inference

Abstract

Theoretical Models of Placebo Analgesia

EEG Measures of Pain and its Anticipation

Pain Anticipation and its Role in Pain Perception

EEG Studies of Placebo Analgesia

Conclusion

References

Chapter 6. Spinal Mechanisms of Placebo Analgesia and Nocebo Hyperalgesia: Descending Inhibitory and Facilitatory Influences

Abstract

Introduction

Pain and Placebo have Dynamic Interactions

Facilitatory Mechanisms

Inhibitory Mechanisms

Conclusion

References

Chapter 7. Spinal and Supraspinal Mechanisms of Placebo Analgesia

Abstract

Acknowledgments

Introduction

The Anatomy of Descending Pain Control

Descending Control in Placebo Analgesia

Placebo Analgesia and the Spinal Cord

Conclusions and Open Questions

References

Chapter 8. Positive and Negative Emotions and Placebo Analgesia

Abstract

Emotion and Motivation

Reduction in Negative Emotions: Methodologic Issues and Empirical Studies

Individual Differences in Negative Emotions and the Effectiveness of Placebo Interventions on Pain

Negative Emotions Reduce the Effectiveness of Opioids

Placebo Analgesia, Emotions, and Opioid Activity

The Nocebo Response: Negative Placebo Effect or Separate Process?

Clinical Implications

Conclusion and Future Perspectives

References

Chapter 9. Placing Placebo in Normal Brain Function with Neuroimaging

Abstract

Acknowledgments

References

Chapter 10. Brain Predictors of Individual Differences in Placebo Responding

Abstract

Acknowledgments

Brain Predictors of Individual Differences in Placebo Responding

Personality and Brain Predictors of Placebo Analgesia

Limitations of Studies on Individual Differences in PA

Solutions

How Can Brain Imaging Studies Find Brain Predictors of PA? Recommendations and Conclusions

References

Chapter 11. Placebo Responses, Antagonistic Responses, and Homeostasis

Abstract

Placebo Responses and Homeostasis

Theoretical Background

Classical Conditioning and Pain

Conditioning with Administration of Painkillers to Pain-Free Subjects

Conditioning with the Administration of Painkillers as the Unconditioned Stimulus to Individuals in Pain

Conditioning with Reduction in, or Absence of, Pain as the US

Conditioning with an Increase in Pain as the US

Active Placebo

Compensatory Responses and the Nocebo Effect

Summary and conclusions

References

Chapter 12. Placebo Analgesia, Nocebo Hyperalgesia, and Acupuncture

Abstract

Is Acupuncture a form of Placebo Treatment?

Challenges and Issues in Placebo/Sham Acupuncture Studies

Subjective and Objective Measurements in Acupuncture and Placebo Studies

Contribution of Neuroimaging to Acupuncture and Placebo/Nocebo Response

Summary and Future Directions

References

Chapter 13. The Relevance of Placebo and Nocebo Mechanisms for Analgesic Treatments

Abstract

Placebo and Nocebo in Pain Treatments: Behavioral Evidence

Understanding the Neural Mechanisms Underlying the Effects of Expectation and Learning on Drug Efficacy

Modulating Expectations to Optimize Analgesic Outcome

Exploiting Learning Mechanisms to Optimize Analgesic Outcome

Future Aims and Challenges

Conclusion

References

Chapter 14. How Placebo Responses are Formed: From Bench to Bedside

Abstract

Acknowledgments

Introduction

Instructional Learning

Associative Learning

Social Learning

Expectations

Evolutionary Principles Behind Placebo Analgesia

Conclusion

Conflicts of Interest

References

Chapter 15. Methodologic Aspects of Placebo Research

Abstract

Acknowledgment

Methodology of Studies Investigating Placebo Analgesia and Nocebo Hyperalgesia

Induced Pain and Clinical Pain

Quantification of Pain

Response Bias

Design

Within-Subjects Versus Between-Subjects Designs

The Pre-Test

Researchers’ and Subjects’ Perception of the Treatment Allocation

Single-Blind Versus Double-Blind Designs

Induction of Placebo Analgesia by Classic Conditioning: Methodological Issues

Measurement of Expectations

Conclusion

References

Chapter 16. Balanced Placebo Design, Active Placebos, and Other Design Features for Identifying, Minimizing and Characterizing the Placebo Response

Abstract

Acknowledgment

Introduction

Minimize versus Maximize

The ‘Additive Model’ Assumptions

The Balanced Placebo Design

The Balanced Cross-Over Design

The ‘Delayed Response’ Test

Active Placebos

Effective Blinding

No-Treatment and Waiting-List Controls

The Free-Choice Paradigm

Ethics of Placebo Research

Summary

References

Chapter 17. Psychological Processes that can Bias Responses to Placebo Treatment for Pain

Abstract

Theoretical Model

Demand Characteristics

The Hawthorne Effect

Response Shift

Returning to the Theoretical Model

Importance of Objective Outcomes

Conclusions and Future Directions

References

Chapter 18. Against ‘Placebo.’ The Case for Changing our Language, and for the Meaning Response

Abstract

A Summary of the Argument

A Brief Review of the Data

Conclusions

References

Chapter 19. Placebo Effects in Complementary and Alternative Medicine: The Self-Healing Response

Abstract

Background

Is CAM ‘All Placebo’? A Note on Specificity and the Efficacy Paradox

Jerome D Frank’s Model of General Healing Effects or Common Factors in Therapy

The Common Myth

The Ritual

Relationship and the Alleviation of Anxiety

Insignia of Power

Empowering Patients and Mobilizing Resources

Summing Up: The Specificity of Nonspecific Effects and the Elegance of Reducing Side-Effects by ‘Placebo’

References

Chapter 20. Conceptualizations and Magnitudes of Placebo Analgesia Effects Across Meta-Analyses and Experimental Studies

Abstract

Acknowledgment

Introduction

Developments in the Conceptualizations and Definitions of Placebo Effects

Meta-Analyses of Placebo Analgesia Effects

Experimental Studies of Factors Influencing the Magnitude of Placebo Analgesia Effects

Current Status of Meta-Analyses of the Magnitude of Placebo Analgesia Effects

References

Chapter 21. The Contribution of Desire, Expectation, and Reduced Negative Emotions to Placebo Anti-Hyperalgesia in Irritable Bowel Syndrome

Abstract

Acknowledgment

Introduction

Evidence for Visceral and Somatic Hyperalgesia in IBS Patients

Visceral and Somatic Hyperalgesia is Dynamically Maintained by Tonic Peripheral Impulse Input

Animal Models of Hyperalgesia in IBS

Psychologic Contributions to Hyperalgesia and Anti-Hyperalgesia in IBS

Central Nervous System Modulation of Pain in IBS

Neurochemical Basis of Anti-Hyperalgesia in Placebo Anti-Hyperalgesic Mechanisms

A Synergistic Interaction between Peripheral Impulse Input and Central Facilitation?

References

Chapter 22. The Wound that Heals: Placebo, Pain and Surgery

Abstract

Background

Placebo and Brain Stimulation for the Treatment of Pain

Conclusions

References

Chapter 23. What are the Best Placebo Interventions for the Treatment of Pain?

Abstract

Introduction

The Efficacy Paradox

Hypotheses from the Literature

Evidence from Direct Comparisons

Evidence from Indirect Comparisons

Discussion

Implications for Clinical Trial Methodology and Decision-Making

Conclusions and Future Directions

References

Chapter 24. How Communication between Clinicians and Patients may Impact Pain Perception

Abstract

Introduction

The Impact of Expectancy in Clinical Studies

The Impact of Emotional Communication

Promoting Patient Involvement and Common Ground: The Patient-Centered Interview

Psychosocial Interventions in Pain Management

Discussion and Conclusion; Suggestions for Future Research

References

Chapter 25. Nocebos in Daily Clinical Practice: The Potential Side Effects of the Treatment Context and the Patient–Doctor Interaction on Pain in Clinical Populations

Abstract

Introduction

Beliefs About Illnesses and Medications

Communicating a Diagnosis and Test Results

Initiating a Treatment

Treatment Implementation

The Role of Treatment Experience

Conclusions

References

Chapter 26. The Potential of the Analgesic Placebo Effect in Clinical Practice – Recommendations for Pain Management

Abstract

Acknowledgment

Introduction

Placebo Responses in Patients

Comparison of Placebo Effects in Healthy Controls and Patients

Use of Placebo Effects in Clinical Practice

Placebo Analgesia: Interactions with Attitudes Towards Medication and Prior Experience

Summary

References

Chapter 27. Placebo and Nocebo: Ethical Challenges and Solutions

Abstract

Acknowledgments

Introduction

Towards Placebos in Clinical Practice

Clinicians’ Attitudes Towards Placebos

Patients’ Attitudes Towards Placebos

Placebos and the Declaration of Helsinki

The Dilemma of Deception

The Impact of the Clinician–Patient Relationship

The Nocebo and its Implications for how Doctors Consult with their Patients

What Translational Research is Being Done, or Should be Done?

References

Index

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