title: The brain signature of paracetamol in healthy volunteers: a double-blind randomized trial.
abstract: BACKGROUND
  Paracetamol's (APAP) mechanism of action suggests the implication of supraspinal structures but no neuroimaging study has been performed in humans.
  
  
  RESULTS
  This randomized, double-blind, crossover, placebo-controlled trial in 17 healthy volunteers (NCT01562704) aimed to evaluate how APAP modulates pain-evoked functional magnetic resonance imaging signals. We used behavioral measures and functional magnetic resonance imaging to investigate the response to experimental thermal stimuli with APAP or placebo administration. Region-of-interest analysis revealed that activity in response to noxious stimulation diminished with APAP compared to placebo in prefrontal cortices, insula, thalami, anterior cingulate cortex, and periaqueductal gray matter.
  
  
  CONCLUSIONS
  These findings suggest an inhibitory effect of APAP on spinothalamic tracts leading to a decreased activation of higher structures, and a top-down influence on descending inhibition. Further binding and connectivity studies are needed to evaluate how APAP modulates pain, especially in the context of repeated administration to patients with pain.
authors.affiliation: CHU Clermont-Ferrand, Centre de Pharmacologie Clinique, Faculté de medicine, France ; Centre d'Investigation Clinique - Inserm 1405, Faculté de medicine, France ; Clermont Université, Laboratoire de Pharmacologie, Faculté de medicine, France.
authors.forename: Gisèle
authors.initials: G
authors.lastname: Pickering
authors.affiliation: CHU Gabriel Montpied, Clermont-Ferrand, Service d'Imagerie Ostéo-articulaire thoracique et neurologique, Clermont-Ferrand, France.
authors.forename: Adrian
authors.initials: A
authors.lastname: Kastler
authors.affiliation: CHU Clermont-Ferrand, Centre de Pharmacologie Clinique, Faculté de medicine, France ; Centre d'Investigation Clinique - Inserm 1405, Faculté de medicine, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Macian
authors.affiliation: CHU Clermont-Ferrand, Délégation Recherche Clinique et à l'Innovation, Clermont-Ferrand, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Pereira
authors.affiliation: Institut du Cerveau et de la Moelle epiniere - ICM, Centre de NeuroImagerie de Recherche CENIR, Inserm U1127, CNRS UMR 7225, Sorbonne Universités, UPMC University Paris, Paris, France, Department of Neuroradiology, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Valabrègue
authors.affiliation: Institut du Cerveau et de la Moelle epiniere - ICM, Centre de NeuroImagerie de Recherche CENIR, Inserm U1127, CNRS UMR 7225, Sorbonne Universités, UPMC University Paris, Paris, France, Department of Neuroradiology, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lehericy
authors.affiliation: CHU Gabriel Montpied, Clermont-Ferrand, Service d'Imagerie Ostéo-articulaire thoracique et neurologique, Clermont-Ferrand, France ; UMR CNRS UdA 6284, Clemont-Ferrand, France.
authors.forename: Louis
authors.initials: L
authors.lastname: Boyer
authors.affiliation: CHU Clermont-Ferrand, Centre de Pharmacologie Clinique, Faculté de medicine, France ; Centre d'Investigation Clinique - Inserm 1405, Faculté de medicine, France ; Clermont Université, Laboratoire de Pharmacologie, Faculté de medicine, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Dubray
authors.affiliation: CHU Gabriel Montpied, Clermont-Ferrand, Service d'Imagerie Ostéo-articulaire thoracique et neurologique, Clermont-Ferrand, France.
authors.forename: Betty
authors.initials: B
authors.lastname: Jean
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology*; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005071:Evoked Potentials / Q000187:drug effects; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010146:Pain / Q000188:drug therapy*; D013133:Spinothalamic Tracts / Q000187:drug effects / Q000378:metabolism; D055815:Young Adult
chemical_list: D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen
keywords: fMRI; nociception; pain; paracetamol; pharmacology