{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T01:23:10Z","timestamp":1777944190706,"version":"3.51.4"},"reference-count":44,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T00:00:00Z","timestamp":1612742400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hungarian Brain Research Program","award":["20017-1.2.1-NKP-2017-00002, NAP2.0"],"award-info":[{"award-number":["20017-1.2.1-NKP-2017-00002, NAP2.0"]}]},{"name":"EFOP","award":["3.6.1-16-2016-00004, 3.6.2-16-2017-00008, and 3.6.2-16-2017-00006"],"award-info":[{"award-number":["3.6.1-16-2016-00004, 3.6.2-16-2017-00008, and 3.6.2-16-2017-00006"]}]},{"name":"FIKPII","award":["17886-4\/23018\/FEKUTSTRAT"],"award-info":[{"award-number":["17886-4\/23018\/FEKUTSTRAT"]}]},{"name":"GINOP","award":["2.3.2-15-2016-00050 \u201cPEPSYS"],"award-info":[{"award-number":["2.3.2-15-2016-00050 \u201cPEPSYS"]}]},{"name":"Hungarian National Scientific Research Fund","award":["KKP129954"],"award-info":[{"award-number":["KKP129954"]}]},{"name":"J\u00e1nos Bolyai Research Scholarship of The Hungarian Academy of Sciences","award":["BO\/00501\/19"],"award-info":[{"award-number":["BO\/00501\/19"]}]},{"name":"New National Excellence Program of the Ministry for Innovation and Technology","award":["\u00daNKP-20-5-PTE-540"],"award-info":[{"award-number":["\u00daNKP-20-5-PTE-540"]}]},{"name":"New National Excellence Program of the Ministry for Innovation and Technology","award":["\u00daNKP-20-3-II-PTE-734"],"award-info":[{"award-number":["\u00daNKP-20-3-II-PTE-734"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Capsaicin-sensitive peptidergic sensory nerves play complex, mainly protective regulatory roles in the inflammatory cascade of the joints via neuropeptide mediators, but the mechanisms of the hyperacute arthritis phase has not been investigated. Therefore, we studied the involvement of these afferents in the early, \u201cblack box\u201d period of a rheumatoid arthritis (RA) mouse model. Capsaicin-sensitive fibres were defunctionalized by pretreatment with the ultrapotent capsaicin analog resiniferatoxin and arthritis was induced by K\/BxN arthritogenic serum. Disease severity was assessed by clinical scoring, reactive oxygen species (ROS) burst by chemiluminescent, vascular permeability by fluorescent in vivo imaging. Contrast-enhanced magnetic resonance imaging was used to correlate the functional and morphological changes. After sensory desensitization, both early phase ROS-burst and vascular leakage were significantly enhanced, which was later followed by the increased clinical severity scores. Furthermore, the early vascular leakage and ROS-burst were found to be good predictors of later arthritis severity. We conclude that the anti-inflammatory role of peptidergic afferents depends on their activity in the hyperacute phase, characterized by decreased cellular and vascular inflammatory components presumably via anti-inflammatory neuropeptide release. Therefore, these fibres might serve as important gatekeepers in RA.<\/jats:p>","DOI":"10.3390\/ijms22041682","type":"journal-article","created":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T23:43:16Z","timestamp":1612914196000},"page":"1682","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Capsaicin-Sensitive Peptidergic Sensory Nerves Are Anti-Inflammatory Gatekeepers in the Hyperacute Phase of a Mouse Rheumatoid Arthritis Model"],"prefix":"10.3390","volume":"22","author":[{"given":"B\u00e1lint","family":"Botz","sequence":"first","affiliation":[{"name":"Department of Medical Imaging, Medical School, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"},{"name":"J\u00e1nos Szent\u00e1gothai Research Centre, Molecular Pharmacology Research Team, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00e1bor","family":"Kriszta","sequence":"additional","affiliation":[{"name":"J\u00e1nos Szent\u00e1gothai Research Centre, Molecular Pharmacology Research Team, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"},{"name":"J\u00e1nos Szent\u00e1gothai Research Centre, NMR Core Facility, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"},{"name":"Department of Pharmacology and Pharmacotherapy, Medical School, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kata","family":"B\u00f6lcskei","sequence":"additional","affiliation":[{"name":"J\u00e1nos Szent\u00e1gothai Research Centre, Molecular Pharmacology Research Team, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"},{"name":"Department of Pharmacology and Pharmacotherapy, Medical School, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4724-8201","authenticated-orcid":false,"given":"\u00c1d\u00e1m Istv\u00e1n","family":"Horv\u00e1th","sequence":"additional","affiliation":[{"name":"J\u00e1nos Szent\u00e1gothai Research Centre, Molecular Pharmacology Research Team, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"},{"name":"Department of Pharmacology and Pharmacotherapy, Medical School, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0512-1157","authenticated-orcid":false,"given":"Attila","family":"M\u00f3csai","sequence":"additional","affiliation":[{"name":"Department of Physiology, Semmelweis University, H-1094 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zsuzsanna","family":"Helyes","sequence":"additional","affiliation":[{"name":"J\u00e1nos Szent\u00e1gothai Research Centre, Molecular Pharmacology Research Team, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"},{"name":"Department of Pharmacology and Pharmacotherapy, Medical School, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"},{"name":"PharmInVivo Ltd., H-7629 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/nrrheum.2015.8","article-title":"Rheumatoid arthritis therapy reappraisal: Strategies, opportunities and challenges","volume":"11","author":"Smolen","year":"2015","journal-title":"Nat. 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