Endocannabinoid and Prostanoid Crosstalk in Pain. Issue 10 (October 2019)

• Record Type: Journal Article
• Authors: Buisseret, Baptiste; Alhouayek, Mireille; Guillemot-Legris, Owein; Muccioli, Giulio G.
• Is Part Of: Trends in molecular medicine. Volume 25:Issue 10(2019)
• Page Start: 882
• Page End: 896
• Publication Date: 2019-10
• Subjects: MAGL -- FAAH -- PGD2-G -- bioactive lipid -- prostamide -- inflammation; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; Physiology, Pathological -- Periodicals; 572.8
• DOI: 10.1016/j.molmed.2019.04.009
• Languages: English
• ISSNs: 1471-4914

Abstract

Abstract : Interfering with endocannabinoid (eCB) metabolism to increase their levels is a proven anti-nociception strategy. However, because the eCB and prostanoid systems are intertwined, interfering with eCB metabolism will affect the prostanoid system and inversely. Key to this connection is the production of the cyclooxygenase (COX) substrate arachidonic acid upon eCB hydrolysis as well as the ability of COX to metabolize the eCBs anandamide (AEA) and 2-arachidonoylglycerol (2-AG) into prostaglandin-ethanolamides (PG-EA) and prostaglandin-glycerol esters (PG-G), respectively. Recent studies shed light on the role of PG-Gs and PG-EAs in nociception and inflammation. Here, we discuss the role of these complex systems in nociception and new opportunities to alleviate pain by interacting with them. Highlights: The eCB and PG systems have been studied separately for a long time. Increasing evidence has revealed a strong connection between the two systems, supporting a change in paradigm whereby both systems are studied together. eCBs and PGs are key players in nociception, acting via peripheral, spinal, and supraspinal mechanisms. As we suggest here, targeting multiple enzymes and receptors will represent new opportunities to treat pain, using the cooperative effects of modulating both the eCB and prostanoid systems. Increasing evidence supports the bioactivity of PG-EA and PG-Gs, including in inflammatory and painful situations.