title: Placebo analgesia: Self-report measures and preliminary evidence of cortical dopamine release associated with placebo response.
abstract: Placebo analgesia is measured by self-report, yet current, expected, and recalled efficacy may be differentially related to brain function. Here we used a human thermal pain model to compare self-reports of expected, concurrent, and recalled efficacy of a topical placebo analgesic, and tested associations of the three measures of efficacy with changes in dopamine D2/D3 receptor availability in brain using [(18)F]fallypride with positron emission tomography (PET). Participants (15 healthy women) were assessed on three test days. The first test day included a laboratory visit, during which the temperature needed to evoke consistent pain was determined, placebo analgesia was induced via verbal and experience-based expectation, and the placebo response was measured. On two subsequent test days, PET scans were performed in Control and Placebo conditions, respectively, in counterbalanced order. During Visit 1, concurrent and recalled placebo efficacy were unrelated; during the Placebo PET visit, expected and recalled efficacy were highly correlated (ρ = 0.68, p = 0.005), but concurrent efficacy was unrelated to expected or recalled efficacy. Region of interest analysis revealed dopamine D2/D3 receptor availability was lower in left ventrolateral prefrontal cortex in the Placebo condition (p < 0.001, uncorrected), and greater change in this measure was associated with higher levels of recalled analgesic efficacy (ρ = 0.58, p = 0.02). These preliminary findings underscore the need to consider how self-reported symptom improvement is assessed in clinical trials of analgesics and suggest that dopaminergic activity in the ventrolateral prefrontal cortex may promote recalled efficacy of placebo.
authors.affiliation: Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Psychology, Stony Brook University, NY, USA.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Jarcho
authors.affiliation: Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Alan Edwards Centre for Research on Pain, Faculty of Dentistry, McGill University, Montreal, QC, Canada.
authors.forename: Natasha A
authors.initials: NA
authors.lastname: Feier
authors.affiliation: Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Medicine, Division of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, CA, United States; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Physiology, UCLA, Los Angeles, CA, United States; Pain and Interoception Network (PAIN), UCLA, Los Angeles, CA, Unit.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Labus
authors.affiliation: Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Medicine, Division of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, CA, United States; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Physiology, UCLA, Los Angeles, CA, United States; Pain and Interoception Network (PAIN), UCLA, Los Angeles, CA, Unit.
authors.forename: Bruce
authors.initials: B
authors.lastname: Naliboff
authors.affiliation: Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Medicine, Division of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, CA, United States; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Physiology, UCLA, Los Angeles, CA, United States; Pain and Interoception Network (PAIN), UCLA, Los Angeles, CA, Unit.
authors.forename: Suzanne R
authors.initials: SR
authors.lastname: Smith
authors.affiliation: Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Medicine, Division of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, CA, United States; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Physiology, UCLA, Los Angeles, CA, United States; Pain and Interoception Network (PAIN), UCLA, Los Angeles, CA, Unit.
authors.forename: Jui-Yang
authors.initials: JY
authors.lastname: Hong
authors.affiliation: School of Nursing, University of Maryland, Baltimore, MD, USA; School of Medicine, University of Maryland, Baltimore, MD, USA.
authors.forename: Luana
authors.initials: L
authors.lastname: Colloca
authors.affiliation: Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Medicine, Division of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, CA, United States; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Physiology, UCLA, Los Angeles, CA, United States; Pain and Interoception Network (PAIN), UCLA, Los Angeles, CA, Unit; VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Tillisch
authors.affiliation: VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Mandelkern
authors.affiliation: Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Medicine, Division of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, CA, United States; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Physiology, UCLA, Los Angeles, CA, United States; Pain and Interoception Network (PAIN), UCLA, Los Angeles, CA, Unit.
authors.forename: Emeran A
authors.initials: EA
authors.lastname: Mayer
authors.affiliation: Department of Physiology, UCLA, Los Angeles, CA, United States; VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Edythe D
authors.initials: ED
authors.lastname: London
mesh_terms: D000328:Adult; D000698:Analgesia / Q000523:psychology*; D001549:Benzamides / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D019788:Fluorodeoxyglucose F18; D006358:Hot Temperature; D006801:Humans; D008279:Magnetic Resonance Imaging; D058748:Pain Perception / Q000502:physiology*; D015990:Placebo Effect; D049268:Positron-Emission Tomography; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D057566:Self Report; D055815:Young Adult
chemical_list: D001549:Benzamides; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D019788:Fluorodeoxyglucose F18; C574003:fallypride; D004298:Dopamine
keywords: PET; Pain; Placebo effect; Ventrolateral prefrontal cortex; [18F]fallypride