Etoricoxib

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Etoricoxib is a non-funded cyclooxygenase-2 (COX-2) inhibitor (see NSAIDs) that has demonstrated efficacy in managing pain, particularly in conditions like osteoarthritis. An RCT indicated that etoricoxib addresses both peripheral and central pain mechanisms.

A randomized, double-blind, placebo-controlled, 2-way crossover study involving patients with painful knee OA investigated the pain mechanisms modulated by etoricoxib (60 mg/day) over a 4-week treatment period. The study found that etoricoxib significantly modulated central pain modulatory mechanisms and improved pain and function in these patients.

The study defined responders based on achieving at least a 30% or 50% reduction in average pain over the last 24 hours (BPI) from day 0 to day 28. Using the 30% pain reduction criterion, 57% of subjects were classified as responders to etoricoxib; with a 50% reduction criterion, 30% were responders. Fascinatingly, among non-responders there was a significant negative correlation between baseline temporal summation and pain alleviation.

The study utilized quantitative sensory testing (QST) to assess the drug's impact on pain mechanisms: pressure pain thresholds (improved), temporal summation (improved), and conditioned pain modulation (no change).

The findings that etoricoxib modulates spreading sensitization (PPTs at a distant site) and temporal summation provide evidence for a central mode of action. Animal studies have previously indicated increased spinal prostaglandin E2 (PGE2) levels after peripheral inflammation, a process involving COX-2 that can be modulated by intrathecally administered COX-2 inhibitors, affecting central sensitization. Human data also suggest that etoricoxib can enter the cerebrospinal fluid, allowing for potential modulation of central sensitization in pain patients. The study's results support the hypothesis that etoricoxib exerts part of its analgesic effect by inhibiting central pain mechanisms associated with sensitization.

Resources

Etoricoxib central effects - arendt-nielsen 2016.pdf - 1.15 MB (f)