title: A prefrontal non-opioid mechanism in placebo analgesia.
abstract: Behavioral studies have suggested that placebo analgesia is partly mediated by the endogenous opioid system. Expanding on these results we have shown that the opioid-receptor-rich rostral anterior cingulate cortex (rACC) is activated in both placebo and opioid analgesia. However, there are also differences between the two treatments. While opioids have direct pharmacological effects, acting on the descending pain inhibitory system, placebo analgesia depends on neocortical top-down mechanisms. An important difference may be that expectations are met to a lesser extent in placebo treatment as compared with a specific treatment, yielding a larger error signal. As these processes previously have been shown to influence other types of perceptual experiences, we hypothesized that they also may drive placebo analgesia. Imaging studies suggest that lateral orbitofrontal cortex (lObfc) and ventrolateral prefrontal cortex (vlPFC) are involved in processing expectation and error signals. We re-analyzed two independent functional imaging experiments related to placebo analgesia and emotional placebo to probe for a differential processing in these regions during placebo treatment vs. opioid treatment and to test if this activity is associated with the placebo response. In the first dataset lObfc and vlPFC showed an enhanced activation in placebo analgesia vs. opioid analgesia. Furthermore, the rACC activity co-varied with the prefrontal regions in the placebo condition specifically. A similar correlation between rACC and vlPFC was reproduced in another dataset involving emotional placebo and correlated with the degree of the placebo effect. Our results thus support that placebo is different from specific treatment with a prefrontal top-down influence on rACC.
authors.affiliation: Cognitive Neurophysiology Research Group, Stockholm Brain Institute, Osher Center for Integrative Medicine, Karolinska Institutet, Stockholm, Sweden Pain Clinic, Department of Anaesthesiology and Intensive Care Medicine, Helsinki University Central Hospital and Institute of Clinical Medicine, University of Helsinki, Finland Cognitive Neuroscience Research Group, IBB/CBME, University of Algarve, Faro, Portugal Oxford Centre for Functional MRI of the Brain, University of Oxford, Oxford, UK.
authors.forename: Predrag
authors.initials: P
authors.lastname: Petrovic
authors.forename: Eija
authors.initials: E
authors.lastname: Kalso
authors.forename: Karl Magnus
authors.initials: KM
authors.lastname: Petersson
authors.forename: Jesper
authors.initials: J
authors.lastname: Andersson
authors.forename: Peter
authors.initials: P
authors.lastname: Fransson
authors.forename: Martin
authors.initials: M
authors.lastname: Ingvar
mesh_terms: D000328:Adult; D000698:Analgesia / Q000379:methods / Q000523:psychology; D000701:Analgesics, Opioid / Q000627:therapeutic use; D001931:Brain Mapping; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D018847:Opioid Peptides / Q000378:metabolism*; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology; D010147:Pain Measurement; D015990:Placebo Effect; D010919:Placebos / Q000627:therapeutic use*; D017397:Prefrontal Cortex / Q000378:metabolism / Q000503:physiopathology*; D012044:Regression Analysis
chemical_list: D000701:Analgesics, Opioid; D018847:Opioid Peptides; D010919:Placebos
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