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Therefore, we performed pain phenotyping, functional neuroimaging, pharmacokinetic\/pharmacodynamic assessments, inflammation biomarkers, and gene expression profiling in healthy subjects who underwent surgical extraction of bony impacted third molars and were treated with ibuprofen (400\u00a0mg; <jats:italic>N<\/jats:italic>\u00a0=\u00a019) or placebo (<jats:italic>N<\/jats:italic>\u00a0=\u00a010). Analgesic efficacy was not associated with demographic or clinical characteristics, ibuprofen pharmacokinetics, or the degree of cyclooxygenase inhibition by ibuprofen. Compared with partial responders to ibuprofen (<jats:italic>N<\/jats:italic>\u00a0=\u00a09, required rescue medication within the dosing interval), complete responders (<jats:italic>N<\/jats:italic>\u00a0=\u00a010, no rescue medication) exhibited greater induction of urinary prostaglandin metabolites and serum tumor necrosis factor\u2010\u03b1 and interleukin 8. Differentially expressed genes in peripheral blood mononuclear cells were enriched for inflammation\u2010related pathways. These findings suggest that a less pronounced activation of the inflammatory prostanoid system is associated with insufficient pain relief on ibuprofen alone and the need for additional therapeutic intervention.<\/jats:p>","DOI":"10.1002\/cpt.1446","type":"journal-article","created":{"date-parts":[[2019,3,31]],"date-time":"2019-03-31T10:59:10Z","timestamp":1554029950000},"page":"632-641","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Variability in the Analgesic Response to Ibuprofen Is Associated With Cyclooxygenase Activation in Inflammatory Pain"],"prefix":"10.1111","volume":"106","author":[{"given":"Katherine N.","family":"Theken","sequence":"first","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliot 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