Effects of R-flurbiprofen and the oxygenated metabolites of endocannabinoids in inflammatory pain mice models.
(2021) The FASEB Journal — Vol. 35, n° 4, p. e21411 [1-16] (2021)
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- by cyclooxygenase (COX)-2, are major bioactive lipids implicated in inflammation and pain. However, COX-2 is also able to metabolize other lipids, including the endocannabinoids 2- arachidonoylglycerol (2-AG) and anandamide (AEA), to give glycerol ester (PG-G) and ethanolamide (PG-EA) derivatives of the PGs. Consequently, COX-2 can be considered as a hub, controlling PG synthesis but also PGG and PG-EA synthesis. As they were more recently characterized, these endocannabinoid metabolites are less studied in nociception compared to PGs. Interestingly R-profens, previously considered as inactive enantiomers of non-steroidal anti-inflammatory drugs (NSAIDs), are substrate-selective COX inhibitors. Indeed, Rflurbiprofen can selectively block PG-G and PG-EA production, without affecting PG synthesis from COX-2. Therefore, we compared the effect of R-flurbiprofen and S-flurbiprofen in models of inflammatory pain triggered by local administration of lipopolysaccharides (LPS) and carrageenan in mice. Remarkably, the effects of flurbiprofen enantiomers on mechanical hyperalgesia seem to depend on (i) the inflammatory stimuli, (ii) the route of administration and (iii) the timing of administration. We also assessed the effect of administration of the PG-Gs, PG-EAs and PGs on LPS-induced mechanical hyperalgesia. Our data support the interest of studying the non-hydrolytic endocannabinoid metabolism in the context of inflammatory pain.
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Buisseret, B., Guillemot-Legris, O., Ben Kouidar, Y., Paquot, A., Muccioli, G., & Al Houayek, M. (2021). Effects of R-flurbiprofen and the oxygenated metabolites of endocannabinoids in inflammatory pain mice models. The FASEB Journal, 35(4), e21411 [1-16]. https://doi.org/10.1096/fj.202002468R (Original work published 2021)