The brain signature of paracetamol in healthy volunteers: a double-blind randomized trial

• Published in: Drug design, development and therapy development and therapy, 2015-01, Vol.9 (default), p.3853-3862
• Main Authors: Pickering, Gisèle, Kastler, Adrian, Macian, Nicolas, Pereira, Bruno, Valabrègue, Romain, Lehericy, Stéphane, Boyer, Louis, Dubray, Claude, Jean, Betty
• Format: Article
• Language: English
• Subjects: Acetaminophen; Acetaminophen - pharmacology; Adult; Analgesics; Analgesics, Non-Narcotic - pharmacology; Brain - drug effects; Brain - metabolism; Brain mapping; Brain research; Clinical trials; Cortex (cingulate); Cross-Over Studies; Dosage and administration; Double-Blind Method; Double-blind studies; Drug metabolism; Evaluation; Evoked Potentials - drug effects; Experiments; Feasibility studies; fMRI; Functional magnetic resonance imaging; Human health and pathology; Humans; Life Sciences; Magnetic Resonance Imaging; Male; Medical imaging; Methods; Neural networks; Neural transmission; Neuroimaging; nociception; Observations; Original Research; Pain; Pain - drug therapy; Pain perception; Paracetamol; Periaqueductal gray area; Pharmacology; Physiological aspects; Resonance; Spinothalamic Tracts - drug effects; Spinothalamic Tracts - metabolism; Substantia grisea; Thermal stimuli; Young Adult
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S81004

Paracetamol's (APAP) mechanism of action suggests the implication of supraspinal structures but no neuroimaging study has been performed in humans. 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. 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.