title: Placebo improves pleasure and pain through opposite modulation of sensory processing.
abstract: Placebo analgesia is often conceptualized as a reward mechanism. However, by targeting only negative experiences, such as pain, placebo research may tell only half the story. We compared placebo improvement of painful touch (analgesia) with placebo improvement of pleasant touch (hyperhedonia) using functional MRI and a crossover design. Somatosensory processing was decreased during placebo analgesia and increased during placebo hyperhedonia. Both placebo responses were associated with similar patterns of activation increase in circuitry involved in emotion appraisal, including the pregenual anterior cingulate, medial orbitofrontal cortex, amygdala, accumbens, and midbrain structures. Importantly, placebo-induced coupling between the ventromedial prefrontal cortex and periaqueductal gray correlated with somatosensory decreases to painful touch and somatosensory increases to pleasant touch. These findings suggest that placebo analgesia and hyperhedonia are mediated by activation of shared emotion appraisal neurocircuitry, which down- or up-regulates early sensory processing, depending on whether the expectation is reduced pain or increased pleasure.
authors.affiliation: Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, S-413 45 Gothenburg, Sweden.
authors.forename: Dan-Mikael
authors.initials: DM
authors.lastname: Ellingsen
authors.forename: Johan
authors.initials: J
authors.lastname: Wessberg
authors.forename: Marie
authors.initials: M
authors.lastname: Eikemo
authors.forename: Jaquette
authors.initials: J
authors.lastname: Liljencrantz
authors.forename: Tor
authors.initials: T
authors.lastname: Endestad
authors.forename: Håkan
authors.initials: H
authors.lastname: Olausson
authors.forename: Siri
authors.initials: S
authors.lastname: Leknes
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D018592:Cross-Over Studies; D004644:Emotions; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010121:Oxytocin; D010146:Pain / Q000139:chemically induced*; D010465:Perception / Q000502:physiology*; D010812:Physical Stimulation; D015990:Placebo Effect; D010919:Placebos / Q000494:pharmacology*; D057181:Pleasure / Q000187:drug effects*
chemical_list: D010919:Placebos; D010121:Oxytocin
keywords: expectancy; hedonic feelings; neuroimaging