title: Haloperidol blocks dorsal striatum activity but not analgesia in a placebo paradigm.
abstract: Although placebo analgesia has been associated with an engagement of the endogenous opioid system there is growing evidence from neuropharmacological studies for an involvement of additional neurotransmitter systems. An increased dopaminergic neurotransmission in the ventral basal ganglia that has been found during placebo analgesia suggests a role for the dopaminergic system (Scott et al., 2007). It is, however, unclear whether striatal dopaminergic activity is causally involved in this type of analgesia. This study aimed at exploring the functional role of the dopaminergic system in placebo analgesia. To this end, we investigated the effect of the dopamine D2/D3 receptor antagonist haloperidol on behavioral and neural measures of placebo analgesia using functional magnetic resonance imaging (fMRI) in healthy volunteers. We found that 2 mg haloperidol p.o. significantly reduced the correlation between dorsal striatum activity and the individual placebo response, but had no significant effect on placebo analgesia at the behavioral or neural level, as indexed by activity in sensory or pain-modulatory brain regions. Our study therefore suggests that dopaminergic neurotransmission might not be causally involved in placebo analgesia but is related to phenomena associated with placebo analgesia such as reward processing and learning.
authors.affiliation: Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Neurology, University Duisburg-Essen, Germany. Electronic address: n.wrobel@uke.de.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Wrobel
authors.affiliation: Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK.
authors.forename: Katja
authors.initials: K
authors.lastname: Wiech
authors.affiliation: Department of Neurology, University Duisburg-Essen, Germany.
authors.forename: Katarina
authors.initials: K
authors.lastname: Forkmann
authors.affiliation: Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Neurology, University Duisburg-Essen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Ritter
authors.affiliation: Department of Neurology, University Duisburg-Essen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bingel
mesh_terms: D000293:Adolescent; D000328:Adult; D000698:Analgesia; D001921:Brain / Q000187:drug effects*; D001931:Brain Mapping; D018492:Dopamine Antagonists / Q000494:pharmacology*; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009434:Neural Pathways / Q000187:drug effects* / Q000502:physiology; D010146:Pain / Q000188:drug therapy*; D010919:Placebos / Q000494:pharmacology; D055815:Young Adult
chemical_list: D018492:Dopamine Antagonists; D010919:Placebos; D006220:Haloperidol
keywords: Dopamine; Haloperidol; Pain; Placebo analgesia; fMRI