• Gisèle Pickering, Adrian Kastler, Nicolas Macian, Bruno Pereira, Romain Valabrègue, Stéphane Lehericy, Louis Boyer, Claude Dubray, and Betty Jean.
• 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.
• Drug Des Dev Ther. 2015 Jan 1; 9: 3853-62.

BackgroundParacetamol's (APAP) mechanism of action suggests the implication of supraspinal structures but no neuroimaging study has been performed in humans.Methods And ResultsThis 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.ConclusionThese 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.

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