Pickering G, et al. - In this randomized double-blind crossover controlled pilot study including 47 Caucasian volunteers, researchers examined how paracetamol pain relief is associated with the genetic polymorphism of 23 enzymes and receptors. At the Clinical Pharmacology Department, University Hospital, Clermont-Ferrand, France, two randomized sessions 1 week apart with oral paracetamol or placebo were implemented among the participants, and pain changes were evaluated with mechanical pain stimuli. Paracetamol vs placebo was antinociceptive (222 ± 482 kPaxmin vs 23 ± 431 kPaxmin). Among participants, 30 were paracetamol responders and 17 were paracetamol nonresponders. TRPV1rs224534 A allele, UGT2B15rs1902023 TT genotype, and SULT1A1rs9282861 GG genotype characterized responders. For the first time, findings confirm that a specific TRPV1 rs224534 variant is involved in paracetamol antinociception. Further, they indicate a novel antinociceptive role for specific variants of hepatic phase II enzymes linked with paracetamol metabolism. Results support performing larger clinical trials on these potential genomic markers of paracetamol analgesia in patients.