Evidence for a central mode of action for etoricoxib (COX-2 Inhibitor) in patients with painful knee osteoarthritis

The COX-2 inhibitor etoricoxib modulates the peripheral and central nociceptive mechanisms in animals. This interaction has not been studied in pain patients. 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/day etoricoxib followed by placebo), or B) (placebo followed by 60 mg/day etoricoxib). The quantitative, mechanistic pain biomarkers were pressure pain thresholds (PPTs), temporal summation (TS), and conditioning pain modulation (CPM). Clinical readouts were Brief Pain Inventory (BPI), WOMAC, PainDetect Questionnaire (PDQ), time and pain intensity during walking and stair climbing.Etoricoxib as compared with placebo significantly modulated the PPTs (P=0.012, localized sensitization) at the knee and leg (control site) (P=0.025, spreading sensitization) and temporal summation assessed from the knee (P=0.038) and leg (P=0.045). CPM was not modulated. The BPI (pain scores), PDQ, WOMAC, walking and stair climbing tests were all significantly improved by etoricoxib. Based on a minimum of 30% or 50% pain alleviation (day 0 to day 28), responders and non-responders were defined. The non-responders 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 temporal summation may indicate a better response to etoricoxib supporting the central mode-of-action of the drug.

SUMMARY: Etoricoxib significantly modulates peripheral/central sensitization and temporal summation in patients with painful knee osteoarthritis.