Related Experiment Video
Updated: Jul 10, 2026

Intracranial Pharmacotherapy and Pain Assays in Rodents
Published on: April 9, 2019
Acetaminophen reinforces descending inhibitory pain pathways
G Pickering1, V Estève, M-A Loriot
1CHU Clermont-Ferrand, Clinical Pharmacology Centre, University Hospital, Clermont-Ferrand, France. gisele.pickering@u- clermont1.fr
Abstract:
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.
Related Concept Videos
Analgesia and Pain Management
Pain
Nociception
Opioid Analgesics: Synthetic and Semisynthetic Opioids
Desensitization and Tachyphylaxis
Several...
Opioid Analgesics: Morphine and Other Natural Cogeners