title: Placebo conditioning and placebo analgesia modulate a common brain network during pain anticipation and perception.
abstract: The neural mechanisms whereby placebo conditioning leads to placebo analgesia remain unclear. In this study we aimed to identify the brain structures activated during placebo conditioning and subsequent placebo analgesia. We induced placebo analgesia by associating a sham treatment with pain reduction and used fMRI to measure brain activity associated with three stages of the placebo response: before, during and after the sham treatment, while participants anticipated and experienced brief laser pain. In the control session participants were explicitly told that the treatment was inactive. The sham treatment group reported a significant reduction in pain rating (p=0.012). Anticipatory brain activity was modulated during placebo conditioning in a fronto-cingulate network involving the left dorsolateral prefrontal cortex (DLPFC), medial frontal cortex and the anterior mid-cingulate cortex (aMCC). Identical areas were modulated during anticipation in the placebo analgesia phase with the addition of the orbitofrontal cortex (OFC). However, during altered pain experience only aMCC, post-central gyrus and posterior cingulate demonstrated altered activity. The common frontal cortical areas modulated during anticipation in both the placebo conditioning and placebo analgesia phases have previously been implicated in placebo analgesia. Our results suggest that the main effect of placebo arises from the reduction of anticipation of pain during placebo conditioning that is subsequently maintained during placebo analgesia.
authors.affiliation: Human Pain Research Group, University of Manchester Rheumatic Diseases Centre, Hope Hospital, Salford M6 8HD, UK. alison.watson@manchester.ac.uk
authors.forename: Alison
authors.initials: A
authors.lastname: Watson
authors.forename: Wael
authors.initials: W
authors.lastname: El-Deredy
authors.forename: Gian Domenico
authors.initials: GD
authors.lastname: Iannetti
authors.forename: Donna
authors.initials: D
authors.lastname: Lloyd
authors.forename: Irene
authors.initials: I
authors.lastname: Tracey
authors.forename: Brent A
authors.initials: BA
authors.lastname: Vogt
authors.forename: Valerie
authors.initials: V
authors.lastname: Nadeau
authors.forename: Anthony K P
authors.initials: AK
authors.lastname: Jones
mesh_terms: D000328:Adult; D000698:Analgesia / Q000379:methods*; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000704:Analysis of Variance; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D001931:Brain Mapping; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007834:Lasers / Q000009:adverse effects; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009415:Nerve Net / Q000098:blood supply / Q000503:physiopathology*; D010100:Oxygen / Q000097:blood; D010146:Pain / Q000188:drug therapy* / Q000523:psychology*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects*; D010919:Placebos / Q000494:pharmacology / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000700:Analgesics; D010919:Placebos; D010100:Oxygen