The specialised pro-resolving lipid mediator maresin 1 reduces inflammatory pain with a long-lasting analgesic effect

Maresin 1 (MaR1) is a specialised pro-resolving lipid mediator with anti-inflammatory and analgesic activities. In this study, we addressed the modulation of peripheral and spinal cord cells by MaR1 in the context of inflammatory pain. Experimental approach: Mice were treated with MaR1 before intraplantar injection of carrageenan or complete Freund's adjuvant (CFA). Mechanical hyperalgesia was assessed using the electronic von Frey and thermal hyperalgesia using a hot plate. Spinal cytokine production and NF-κB activation were determined by ELISA and astrocytes and microglia activation by RT-qPCR and immunofluorescence. CGRP release by dorsal root ganglia (DRG) neurons was determined by EIA. Neutrophil and macrophage recruitment were determined by immunofluorescence, flow cytometry, and colorimetric

Maresin 1 (MaR1) is a specialised pro-resolving lipid mediator with anti-inflammatory and analgesic activities. In this study, we addressed the modulation of peripheral and spinal cord cells by MaR1 in the context of inflammatory pain. Experimental approach: Mice were treated with MaR1 before intraplantar injection of carrageenan or complete Freund's adjuvant (CFA). Mechanical hyperalgesia was assessed using the electronic von Frey and thermal hyperalgesia using a hot plate. Spinal cytokine production and NF-κB activation were determined by ELISA and astrocytes and microglia activation by RT-qPCR and immunofluorescence. CGRP release by dorsal root ganglia (DRG) neurons was determined by EIA. Neutrophil and macrophage recruitment were determined by immunofluorescence, flow cytometry, and colorimetric

MaR1 reduced carrageenan- and CFA-induced mechanical and thermal hyperalgesia and neutrophil and macrophage recruitment proximal to CGRP+ fibres in the paw skin. Moreover, MaR1 reduced NF-κB activation, IL-1β and TNF-α production, and spinal cord glial cells activation. In the DRG, MaR1 reduced CFA-induced Nav1.8 and Trpv1 mRNA expression and calcium influx and capsaicin-induced release of CGRP by DRG neurons. Conclusions and implications: MaR1 reduced DRG neurons activation and CGRP release explaining, at least in part, its analgesic and anti-inflammatory effects. The enduring analgesic and anti-inflammatory effects and also post-treatment activity of MaR1 suggest that specialised pro-resolving lipid mediators have potential as a new class of drugs for the treatment of inflammatory pain.