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Current therapies are often ineffective in reducing gout\u2010related pain. Resolvin D1 (RvD1) is a specialized pro\u2010resolving lipid mediator with anti\u2010inflammatory 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>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\u20101\u03b2 production was measured by ELISA. Phosphorylated NF\u2010kB and apoptosis\u2010associated speck\u2010like protein containing CARD (ASC) were detected by immunofluorescence, and mRNA expression was determined by RT\u2010qPCR. CGRP release was determined by EIA and immunofluorescence. MSU crystal phagocytosis was evaluated by confocal microscopy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>RvD1 inhibited MSU\u2010induced mechanical hyperalgesia in a dose\u2010 and time\u2010dependent manner by reducing leukocyte recruitment and IL\u20101\u03b2 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\u20101\u03b2 production by macrophages. RvD1 downmodulated this phenomenon directly by acting on macrophages, and indirectly by inhibiting CGRP release and CGRP\u2010dependent activation of macrophages.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>This study reveals a hitherto unknown neuro\u2010immune axis in gouty arthritis that is targeted by RvD1.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15897","type":"journal-article","created":{"date-parts":[[2022,6,18]],"date-time":"2022-06-18T17:34:25Z","timestamp":1655573665000},"page":"4500-4515","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["RvD1 disrupts nociceptor neuron and macrophage activation and neuroimmune communication, reducing pain and inflammation in gouty arthritis in mice"],"prefix":"10.1111","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7233-477X","authenticated-orcid":false,"given":"Tiago 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