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Capsaicin, the active ingredient in chili pepper and a direct agonist of the transient receptor potential vanilloid (TRPV1) channel, is used clinically to treat neuropathic pain. We previously demonstrated immunomodulatory and antioxidative effects of capsaicin in experimental autoimmune neuritis in vivo and Schwann cells (SC) in vitro. However, the molecular mechanisms underlying the maintenance of axonal integrity in dorsal root ganglion (DRG) and SC homeostasis remain unclear. In this study, we described the effects of capsaicin on DRG and SC in vitro under both na\u00efve and S-Nitroso-N-acetyl-DL-penicillamine (SNAP)-induced oxidative stress conditions. Capsaicin induced an upregulation of the antioxidative cascade involving Nrf2, Ho-1, and Nqo1 in na\u00efve DRG neurons and restored axonal growth under preventive and therapeutic settings. Preventive treatment enhanced catalase expression, whereas treatment increased regeneration-associated Gap43 and Atf3. Inhibition of TRPV1 with capsazepine partly attenuated the protective effect of axonal outgrowth, indicating TRPV1-mediated neuroprotection. In SC, capsaicin increased mitochondrial ATP production and spare respiratory capacity, inducing a transient Nrf2-dependent antioxidant response. Capsaicin suppressed expression of myelination markers under basal conditions but promoted expression of myelination- and repair-associated markers under oxidative stress. The findings support capsaicin as a regulator of neuronal and Schwann cell oxidative stress adaptation.<\/jats:p>","DOI":"10.3390\/cells15131142","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T07:57:24Z","timestamp":1782287844000},"page":"1142","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["TRPV1 Agonist Capsaicin Enhances Oxidative-Stress Resistance and Regeneration in Dorsal Root Ganglia and Schwann Cells"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6726-3125","authenticated-orcid":false,"given":"Baffour Kyei","family":"Sarpong","sequence":"first","affiliation":[{"name":"Department of Neurology, St. Josef-Hospital, Ruhr University Bochum, Gudrunstr. 56, 44791 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0283-5832","authenticated-orcid":false,"given":"Niklas","family":"Rilke","sequence":"additional","affiliation":[{"name":"Department of Neurology, St. Josef-Hospital, Ruhr University Bochum, Gudrunstr. 56, 44791 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5642-267X","authenticated-orcid":false,"given":"Lea","family":"Joswig","sequence":"additional","affiliation":[{"name":"Department of Neurology, St. Josef-Hospital, Ruhr University Bochum, Gudrunstr. 56, 44791 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Finn","family":"Specht","sequence":"additional","affiliation":[{"name":"Department of Neurology, St. Josef-Hospital, Ruhr University Bochum, Gudrunstr. 56, 44791 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona Shaygan","family":"Tabar","sequence":"additional","affiliation":[{"name":"Department of Neurology, St. Josef-Hospital, Ruhr University Bochum, Gudrunstr. 56, 44791 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Blusch","sequence":"additional","affiliation":[{"name":"Brain Disease Biomarker Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Medical Faculty, Lund University, 223 62 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1229-5808","authenticated-orcid":false,"given":"Anna","family":"Meichsner","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia","family":"Renk","sequence":"additional","affiliation":[{"name":"Department of Neurology, St. Josef-Hospital, Ruhr University Bochum, Gudrunstr. 56, 44791 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3024-3826","authenticated-orcid":false,"given":"Xiomara","family":"Pedreiturria","sequence":"additional","affiliation":[{"name":"Department of Neurology, St. Josef-Hospital, Ruhr University Bochum, Gudrunstr. 56, 44791 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8927-9818","authenticated-orcid":false,"given":"Thomas","family":"Gr\u00fcter","sequence":"additional","affiliation":[{"name":"Department of Neurology, St. Josef-Hospital, Ruhr University Bochum, Gudrunstr. 56, 44791 Bochum, Germany"},{"name":"Department of Neurology and Stroke Unit, Klinikum Lippstadt, 59555 Lippstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5989-2195","authenticated-orcid":false,"given":"Rafael","family":"Klimas","sequence":"additional","affiliation":[{"name":"Department of Neurology, St. Josef-Hospital, Ruhr University Bochum, Gudrunstr. 56, 44791 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstanze F.","family":"Winklhofer","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Gold","sequence":"additional","affiliation":[{"name":"Department of Neurology, St. Josef-Hospital, Ruhr University Bochum, Gudrunstr. 56, 44791 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Sgodzai","sequence":"additional","affiliation":[{"name":"Department of Neurology, St. Josef-Hospital, Ruhr University Bochum, Gudrunstr. 56, 44791 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2483-4929","authenticated-orcid":false,"given":"Kalliopi","family":"Pitarokoili","sequence":"additional","affiliation":[{"name":"Department of Neurology, St. Josef-Hospital, Ruhr University Bochum, Gudrunstr. 56, 44791 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1111\/ene.15156","article-title":"Axonal damage determines clinical disability in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): A prospective cohort study of different CIDP subtypes and 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