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Acetaminophen Reinforces Descending Inhibitory Pain Pathways
Author(s) -
Pickering G,
Estève V,
Loriot MA,
Eschalier A,
Dubray C
Publication year - 2008
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/sj.clpt.6100403
Subject(s) - tropisetron , acetaminophen , serotonergic , pharmacology , analgesic , anesthesia , medicine , clinical pharmacology , cold pressor test , placebo , serotonin , receptor , heart rate , alternative medicine , pathology , blood pressure
The mechanism of the analgesic action of acetaminophen involves the serotonergic system. This study explores how acetaminophen interferes with serotonergic descending pain pathways. Eighteen rapid metabolizers of tropisetron were included in this double‐blind cross‐over study. After ethical approval, the healthy volunteers took 1 g oral acetaminophen (A) or placebo (p) combined with either the 5‐HT3 antagonist tropisetron (T) (5 mg) or saline, intravenously, at weekly intervals. Mechanical pain thresholds, determined before and after a cold pressor test (CPT), were repeated seven times during the three post‐dosing hours, and area under the concentration–time curves (AUCs) of the three treatments were compared. After CPT, AUC (%*min) of Ap (1,561±429) was larger than before CPT (393±382, P <0.05); these effects were totally inhibited by tropisetron. Acetaminophen reinforces descending inhibitory pain pathways; it suggests a supraspinal target for acetaminophen's antinociceptive action. This study also confirmed that there is a central serotonergic mechanism of action for acetaminophen that is not stimulus‐dependent. Clinical Pharmacology & Therapeutics (2008); 84 , 1, 47–51 doi: 10.1038/sj.clpt.6100403