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Br J Pharmacol. 2019 Mar 4. doi: 10.1111/bph.14647. [Epub ahead of print]

The specialized pro-resolving lipid mediator Maresin-1 reduces inflammatory pain with a long-lasting analgesic effect.

Author information

1
Departament of Pathology, Centre of Biological Sciences, Londrina State University, Londrina, Paraná, Brazil.
2
Departament of Pharmaceutical Sciences, Centre of Health Science, Londrina State University, Londrina, Paraná, Brazil.

Abstract

BACKGROUND:

MaR1 is a specialized 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 inflammatory pain context.

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 methods. Trpv1 and Nav1.8 expression and calcium imaging of DRG neurons were determined by RT-qPCR and Fluo-4AM, respectively.

KEY RESULTS:

MaR1 reduced carrageenan- and CFA-induced mechanical and thermal hyperalgesia, and neutrophil and macrophage recruitment proximal to CGRP+ fibers 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:

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 the specialized pro-resolving lipid mediators may become a new class of drugs important for the treatment of inflammatory pain.

KEYWORDS:

chronic pain; glial cells; omega-3 fatty acids; pain treatment; spontaneous pain

PMID:
30830967
DOI:
10.1111/bph.14647

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