British journal of pharmacology, 2019-06, Vol.176 (11), p.1728-1744
2019
Details
- Autor(en) / Beteiligte
- Titel
- The specialised pro‐resolving lipid mediator maresin 1 reduces inflammatory pain with a long‐lasting analgesic effect
- Ist Teil von
- British journal of pharmacology, 2019-06, Vol.176 (11), p.1728-1744
- Ort / Verlag
- England: Blackwell Publishing Ltd
- Erscheinungsjahr
- 2019
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Background and Purpose 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 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+ 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0007-1188eISSN: 1476-5381DOI: 10.1111/bph.14647Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6514290
- Format
- –
- Schlagworte
- Activation, Analgesics, Analgesics - pharmacology, Analgesics - therapeutic use, Animals, Anti-Inflammatory Agents - pharmacology, Anti-Inflammatory Agents - therapeutic use, Astrocytes, Calcitonin gene-related peptide, Calcitonin Gene-Related Peptide - metabolism, Calcium, Calcium imaging, Calcium influx, Capsaicin, Capsaicin receptors, Carrageenan, Colorimetry, Docosahexaenoic Acids - pharmacology, Docosahexaenoic Acids - therapeutic use, Dorsal root ganglia, Enzyme-linked immunosorbent assay, Fibers, Flow cytometry, Freund's Adjuvant, Ganglia, Spinal - drug effects, Gene expression, Glial cells, Hot Temperature, Hyperalgesia, Hyperalgesia - drug therapy, Hyperalgesia - genetics, Hyperalgesia - metabolism, Immunofluorescence, Inflammation, Interleukin-1beta - metabolism, Lipids, Macrophages, Male, Mice, Microglia, NAV1.8 Voltage-Gated Sodium Channel - genetics, Neurons, Neurons - drug effects, Neutrophils, NF-kappa B - metabolism, Pain, Pain - drug therapy, Pain - genetics, Pain - metabolism, Pain perception, Physical Stimulation, Research Paper, Research Papers, Skin, Sodium channels (voltage-gated), Spinal cord, Spinal Cord - drug effects, Spinal Cord - metabolism, TRPV Cation Channels - genetics, Tumor necrosis factor, Tumor Necrosis Factor-alpha - metabolism