{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T11:48:48Z","timestamp":1778932128268,"version":"3.51.4"},"reference-count":134,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T00:00:00Z","timestamp":1675123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Porto\/Faculty of Medicine","award":["NORTE-08-5369-FSE-000011"],"award-info":[{"award-number":["NORTE-08-5369-FSE-000011"]}]},{"name":"Funda\u00e7\u00e3o Gr\u00fcnenthal Portugal","award":["NORTE-08-5369-FSE-000011"],"award-info":[{"award-number":["NORTE-08-5369-FSE-000011"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>NADPH oxidase isoform-2 (NOX2) has been implicated in the pathophysiology of neuropathic pain (NP), mostly through the modulation of neuroinflammation. Since it is also accepted that some neuroimmune mechanisms underlying NP are sex-dependent, we aimed to evaluate the effects of early systemic treatment with the NOX2-selective inhibitor (NOX2i) GSK2795039 on behavioral responses and spinal neuroinflammation in spared nerve injury (SNI)-induced NP in male and female mice. Mechanical sensitivity was evaluated with the von Frey test, while general well-being and anxiety-like behavior were assessed with burrowing and light\/dark box tests. Spinal microglial activation and cytokines IL-1\u03b2, IL-6, and IL-10, as well as macrophage colony-stimulating factor (M-CSF) were evaluated by immunofluorescence and multiplex immunoassay, respectively. NOX2i treatment reduced SNI-induced mechanical hypersensitivity and early SNI-induced microglial activation in both sexes. SNI-females, but not males, showed a transient reduction in burrowing activity. NOX2i treatment did not improve their burrowing activity, but tendentially reduced their anxiety-like behavior. NOX2i marginally decreased IL-6 in females, and increased M-CSF in males. Our findings suggest that NOX2-selective inhibition may be a potential therapeutic strategy for NP in both male and female individuals, with particular interest in females due to its apparent favorable impact in anxiety-like behavior.<\/jats:p>","DOI":"10.3390\/biomedicines11020416","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T03:22:47Z","timestamp":1675221767000},"page":"416","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Effects of NADPH Oxidase Isoform-2 (NOX2) Inhibition on Behavioral Responses and Neuroinflammation in a Mouse Model of Neuropathic Pain"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7729-9010","authenticated-orcid":false,"given":"Lu\u00edsa","family":"Teixeira-Santos","sequence":"first","affiliation":[{"name":"Departamento de Biomedicina\u2014Unidade de Farmacologia e Terap\u00eautica, Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal"},{"name":"Centro de Investiga\u00e7\u00e3o Farmacol\u00f3gica e Inova\u00e7\u00e3o Medicamentosa (MedInUP), Universidade do Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2900-6700","authenticated-orcid":false,"given":"Eduardo","family":"Ver\u00edssimo","sequence":"additional","affiliation":[{"name":"Departamento de Biomedicina\u2014Unidade de Farmacologia e Terap\u00eautica, Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal"},{"name":"Centro de Investiga\u00e7\u00e3o Farmacol\u00f3gica e Inova\u00e7\u00e3o Medicamentosa (MedInUP), Universidade do Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6813-314X","authenticated-orcid":false,"given":"Sandra","family":"Martins","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Patologia Cl\u00ednica, Centro Hospitalar e Universit\u00e1rio S\u00e3o Jo\u00e3o (CHUSJ), 4200-319 Porto, Portugal"},{"name":"EPIUnit, Instituto de Sa\u00fade P\u00fablica, Universidade do Porto, 4050-600 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7230-5020","authenticated-orcid":false,"given":"Teresa","family":"Sousa","sequence":"additional","affiliation":[{"name":"Departamento de Biomedicina\u2014Unidade de Farmacologia e Terap\u00eautica, Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal"},{"name":"Centro de Investiga\u00e7\u00e3o Farmacol\u00f3gica e Inova\u00e7\u00e3o Medicamentosa (MedInUP), Universidade do Porto, 4200-319 Porto, Portugal"}]},{"given":"Ant\u00f3nio","family":"Albino-Teixeira","sequence":"additional","affiliation":[{"name":"Departamento de Biomedicina\u2014Unidade de Farmacologia e Terap\u00eautica, Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal"},{"name":"Centro de Investiga\u00e7\u00e3o Farmacol\u00f3gica e Inova\u00e7\u00e3o Medicamentosa (MedInUP), Universidade do Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6965-8597","authenticated-orcid":false,"given":"Dora","family":"Pinho","sequence":"additional","affiliation":[{"name":"Departamento de Biomedicina\u2014Unidade de Farmacologia e Terap\u00eautica, Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal"},{"name":"Centro de Investiga\u00e7\u00e3o Farmacol\u00f3gica e Inova\u00e7\u00e3o Medicamentosa (MedInUP), Universidade do Porto, 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17002","DOI":"10.1038\/nrdp.2017.2","article-title":"Neuropathic pain","volume":"3","author":"Colloca","year":"2017","journal-title":"Nat. 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