RvD1 disrupts nociceptor neuron and macrophage activation and neuroimmune communication, reducing pain and inflammation in gouty arthritis in mice.

Autor: Zaninelli TH; Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Centre of Biological Sciences, Londrina State University, Londrina, Paraná, Brazil., Fattori V; Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Centre of Biological Sciences, Londrina State University, Londrina, Paraná, Brazil.; Vascular Biology Program, Department of Surgery, Boston Children's Hospital-Harvard Medical School, Boston, Massachusetts, USA., Saraiva-Santos T; Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Centre of Biological Sciences, Londrina State University, Londrina, Paraná, Brazil., Badaro-Garcia S; Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Centre of Biological Sciences, Londrina State University, Londrina, Paraná, Brazil., Staurengo-Ferrari L; Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Centre of Biological Sciences, Londrina State University, Londrina, Paraná, Brazil., Andrade KC; Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Centre of Biological Sciences, Londrina State University, Londrina, Paraná, Brazil., Artero NA; Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Centre of Biological Sciences, Londrina State University, Londrina, Paraná, Brazil., Ferraz CR; Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Centre of Biological Sciences, Londrina State University, Londrina, Paraná, Brazil., Bertozzi MM; Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Centre of Biological Sciences, Londrina State University, Londrina, Paraná, Brazil., Rasquel-Oliveira F; Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Centre of Biological Sciences, Londrina State University, Londrina, Paraná, Brazil., Manchope MF; Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Centre of Biological Sciences, Londrina State University, Londrina, Paraná, Brazil., Amaral FA; Department of Biochemistry and Immunology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Brazil., Teixeira MM; Department of Biochemistry and Immunology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Brazil., Borghi SM; Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Centre of Biological Sciences, Londrina State University, Londrina, Paraná, Brazil., Rogers MS; Vascular Biology Program, Department of Surgery, Boston Children's Hospital-Harvard Medical School, Boston, Massachusetts, USA., Casagrande R; Laboratory of Antioxidants and Inflammation, Department of Pharmaceutical Sciences, Centre of Health Sciences, Londrina State University, Londrina, Paraná, Brazil., Verri WA Jr; Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Centre of Biological Sciences, Londrina State University, Londrina, Paraná, Brazil.
Jazyk: angličtina
Zdroj: British journal of pharmacology [Br J Pharmacol] 2022 Sep; Vol. 179 (18), pp. 4500-4515. Date of Electronic Publication: 2022 Jul 07.
DOI: 10.1111/bph.15897
Abstrakt: Background and Purpose: Gouty arthritis is characterized by an intense inflammatory response to monosodium urate crystals (MSU), which induces severe pain. Current therapies are often ineffective in reducing gout-related pain. Resolvin D1 (RvD1) is a specialized pro-resolving lipid mediator with anti-inflammatory and analgesic proprieties. In this study, we evaluated the effects and mechanisms of action of RvD1 in an experimental mouse model of gouty arthritis, an aim that was not pursued previously in the literature.
Experimental Approach: Male mice were treated with RvD1 (intrathecally or intraperitoneally) before or after intraarticular stimulation with MSU. Mechanical hyperalgesia was assessed using an electronic von Frey aesthesiometer. Leukocyte recruitment was determined by knee joint wash cell counting and immunofluorescence. IL-1β production was measured by ELISA. Phosphorylated NF-kB and apoptosis-associated speck-like protein containing CARD (ASC) were detected by immunofluorescence, and mRNA expression was determined by RT-qPCR. CGRP release was determined by EIA and immunofluorescence. MSU crystal phagocytosis was evaluated by confocal microscopy.
Key Results: RvD1 inhibited MSU-induced mechanical hyperalgesia in a dose- and time-dependent manner by reducing leukocyte recruitment and IL-1β production in the knee joint. Intrathecal RvD1 reduced the activation of peptidergic neurons and macrophages as well as silenced nociceptor to macrophage communication and macrophage function. CGRP stimulated MSU phagocytosis and IL-1β production by macrophages. RvD1 downmodulated this phenomenon directly by acting on macrophages, and indirectly by inhibiting CGRP release and CGRP-dependent activation of macrophages.
Conclusions and Implications: This study reveals a hitherto unknown neuro-immune axis in gouty arthritis that is targeted by RvD1.
(© 2022 British Pharmacological Society.)
Databáze: MEDLINE
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