title: Neural mechanisms mediating the effects of expectation in visceral placebo analgesia: an fMRI study in healthy placebo responders and nonresponders.
abstract: This functional magnetic resonance imaging study analysed the behavioural and neural responses during expectation-mediated placebo analgesia in a rectal pain model in healthy subjects. In N=36 healthy subjects, the blood oxygen level-dependent (BOLD) response during cued anticipation and painful rectal stimulation was measured. Using a within-subject design, placebo analgesia was induced by changing expectations regarding the probability of receiving an analgesic drug to 0%, 50%, and 100%. Placebo responders were identified by median split based on pain reduction (0% to 100% conditions), and changes in neural activation correlating with pain reduction in the 0% and 100% conditions were assessed in a regions-of-interest analysis. Expectation of pain relief resulted in overall reductions in pain and urge to defecate, and this response was significantly more pronounced in responders. Within responders, pain reduction correlated with reduced activation of dorsolateral and ventrolateral prefrontal cortices, somatosensory cortex, and thalamus during cued anticipation (paired t tests on the contrast 0%>100%); during painful stimulation, pain reduction correlated with reduced activation of the thalamus. Compared with nonresponders, responders demonstrated greater placebo-induced decreases in activation of dorsolateral prefrontal cortex during anticipation and in somatosensory cortex, posterior cingulate cortex, and thalamus during pain. In conclusion, the expectation of pain relief can substantially change perceived painfulness of visceral stimuli, which is associated with activity changes in the thalamus, prefrontal, and somatosensory cortices. Placebo analgesia constitutes a paradigm to elucidate psychological components of the pain response relevant to the pathophysiology and treatment of chronic abdominal pain.
authors.affiliation: Institute of Medical Psychology and Behavioral Immunobiology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany Institute of Medical Psychology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Neuroimage Nord, Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany Department of Neuroradiology, Centre for Radiology, University Clinic of Gießen and Marburg, Justus-Liebig-University Gießen, Gießen, Germany.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Elsenbruch
authors.forename: Vassilios
authors.initials: V
authors.lastname: Kotsis
authors.forename: Sven
authors.initials: S
authors.lastname: Benson
authors.forename: Christina
authors.initials: C
authors.lastname: Rosenberger
authors.forename: Daniel
authors.initials: D
authors.lastname: Reidick
authors.forename: Manfred
authors.initials: M
authors.lastname: Schedlowski
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bingel
authors.forename: Nina
authors.initials: N
authors.lastname: Theysohn
authors.forename: Michael
authors.initials: M
authors.lastname: Forsting
authors.forename: Elke R
authors.initials: ER
authors.lastname: Gizewski
mesh_terms: D000293:Adolescent; D000328:Adult; D000698:Analgesia / Q000379:methods* / Q000523:psychology*; D001294:Attitude to Health; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods / Q000592:standards; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement / Q000379:methods; D015990:Placebo Effect; D059265:Visceral Pain / Q000503:physiopathology / Q000523:psychology* / Q000628:therapy*; D055815:Young Adult