title: Evidence for a central mode of action for etoricoxib (COX-2 inhibitor) in patients with painful knee osteoarthritis.
abstract: The COX-2 inhibitor etoricoxib modulates the peripheral and central nociceptive mechanisms in animals. This interaction has not been studied in patients with pain. This randomized, double-blind, placebo-controlled, 2-way crossover, 4-week treatment study investigated the pain mechanisms modulated by etoricoxib in patients with painful knee osteoarthritis. Patients were randomized to group A (60 mg/d etoricoxib followed by placebo) or B (placebo followed by 60 mg/d etoricoxib). The quantitative, mechanistic pain biomarkers were pressure pain thresholds, temporal summation (TS), and conditioning pain modulation. Clinical readouts were Brief Pain Inventory, WOMAC, painDETECT questionnaire (PD-Q), and time and pain intensity during walking and stair climbing. Etoricoxib as compared with placebo significantly modulated the pressure pain thresholds (P = 0.012, localized sensitization) at the knee and leg (control site) (P = 0.025, spreading sensitization) and TS assessed from the knee (P = 0.038) and leg (P = 0.045). Conditioning pain modulation was not modulated. The Brief Pain Inventory (pain scores), PD-Q, WOMAC, and walking and stair climbing tests were all significantly improved by etoricoxib. Based on a minimum of 30% or 50% pain alleviation (day 0-day 28), responders and nonresponders were defined. The nonresponders showed a significant association between increased facilitation of TS and increased pain alleviation. None of the other parameters predicted the degree of pain alleviation. Generally, a responder to etoricoxib has the most facilitated TS. In conclusion, etoricoxib (1) modulated central pain modulatory mechanisms and (2) improved pain and function in painful osteoarthritis. Stronger facilitation of TS may indicate a better response to etoricoxib, supporting the central mode-of-action of the drug.
authors.affiliation: SMI, Translational Pain Biomarker Group, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark.|C4Pain, Aalborg, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Arendt-Nielsen
authors.affiliation: SMI, Translational Pain Biomarker Group, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark.|C4Pain, Aalborg, Denmark.
authors.forename: Line Lindhardt
authors.initials: LL
authors.lastname: Egsgaard
authors.affiliation: SMI, Translational Pain Biomarker Group, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark.
authors.forename: Kristian Kjær
authors.initials: KK
authors.lastname: Petersen
mesh_terms: D000368:Aged; D059333:Central Nervous System Sensitization / Q000187:drug effects* / Q000502:physiology; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D000077613:Etoricoxib; D005260:Female; D006801:Humans; D007719:Knee Joint / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000503:physiopathology; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D013450:Sulfones / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011725:Pyridines; D013450:Sulfones; D000077613:Etoricoxib