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Technology, and State Secretariat of Science, Technology, and Higher Education (SETI)","award":["#4560.19.571.06.6153"],"award-info":[{"award-number":["#4560.19.571.06.6153"]}]},{"name":"Government of the State of Paran\u00e1, Paran\u00e1 Council of Science and Technology, and State Secretariat of Science, Technology, and Higher Education (SETI)","award":["21.234.745-0"],"award-info":[{"award-number":["21.234.745-0"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>For centuries, researchers have been fascinated by the composition of scorpion venom and its local and systemic effects on humans. During a sting, scorpions inject peptides and proteins that can affect immune cells and neurons. While the immune and nervous systems have been studied independently in the context of scorpion stings, here we reveal part of the mechanism by which Tityus serrulatus venom induces hyperalgesia in mice. Through behavioral, immune, imaging assays, and mice genetics, we demonstrate evidence of neuroimmune crosstalk during scorpion stings. Tityus serrulatus venom induced mechanical and thermal hyperalgesia in a dose-dependent manner, as well as overt pain-like behavior. The venom directly activated dorsal root ganglia neurons and increased the recruitment of macrophages and neutrophils, releasing pro-inflammatory cytokines TNF-\u03b1 and IL-1\u03b2. Blocking TRPV1+ neurons, TNF-\u03b1, IL-1\u03b2, and NF\u03baB reduced the mechanical and thermal hyperalgesia, overt pain-like behavior, and the migration of macrophages and neutrophils induced by Tityus serrulatus venom. Collectively, Tityus serrulatus venom targets primary afferent nociceptive TRPV1+ neurons to induce hyperalgesia through the recruitment of macrophages and neutrophils and the release of pro-inflammatory cytokines.<\/jats:p>","DOI":"10.3390\/toxins17070332","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T12:10:31Z","timestamp":1751285431000},"page":"332","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Tityus serrulatus Scorpion Venom-Induced Nociceptive Responses Depend on TRPV1, Immune Cells, and Pro-Inflammatory Cytokines"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4550-0773","authenticated-orcid":false,"given":"Camila R.","family":"Ferraz","sequence":"first","affiliation":[{"name":"Department of Immunology, Parasitology and General Pathology, Londrina State University, Londrina 86057-970, Paran\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2882-6536","authenticated-orcid":false,"given":"Mar\u00edlia F.","family":"Manchope","sequence":"additional","affiliation":[{"name":"Department of Immunology, Parasitology and General Pathology, Londrina State University, Londrina 86057-970, Paran\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0551-4313","authenticated-orcid":false,"given":"Mariana M.","family":"Bertozzi","sequence":"additional","affiliation":[{"name":"Department of Immunology, Parasitology and General Pathology, Londrina State University, Londrina 86057-970, Paran\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Telma","family":"Saraiva-Santos","sequence":"additional","affiliation":[{"name":"Department of Immunology, Parasitology and General Pathology, Londrina State University, Londrina 86057-970, Paran\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ketlem C.","family":"Andrade","sequence":"additional","affiliation":[{"name":"Department of Immunology, Parasitology and General Pathology, Londrina State University, Londrina 86057-970, Paran\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4643-2322","authenticated-orcid":false,"given":"Anelise","family":"Franciosi","sequence":"additional","affiliation":[{"name":"Department of Immunology, Parasitology and General Pathology, Londrina State University, Londrina 86057-970, Paran\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7233-477X","authenticated-orcid":false,"given":"Tiago H.","family":"Zaninelli","sequence":"additional","affiliation":[{"name":"Department of Immunology, Parasitology and General Pathology, Londrina State University, Londrina 86057-970, Paran\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Bagatim-Souza","sequence":"additional","affiliation":[{"name":"Department of Immunology, Parasitology and General Pathology, Londrina State University, Londrina 86057-970, Paran\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6978-7505","authenticated-orcid":false,"given":"Sergio M.","family":"Borghi","sequence":"additional","affiliation":[{"name":"Department of Immunology, Parasitology and General Pathology, Londrina State University, Londrina 86057-970, Paran\u00e1, Brazil"},{"name":"Center for Research in Health Sciences, University of Northern Paran\u00e1, Londrina 86057-970, Paran\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise M.","family":"C\u00e2ndido","sequence":"additional","affiliation":[{"name":"Arthropod Laboratory, Butantan Institute, S\u00e3o Paulo 05503-900, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thiago M.","family":"Cunha","sequence":"additional","affiliation":[{"name":"Center of Research in Inflammatory Diseases, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14049-900, S\u00e3o Paulo, Brazil"},{"name":"Department of Pharmacology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14049-900, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2296-1668","authenticated-orcid":false,"given":"Rubia","family":"Casagrande","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Centre of Health Sciences, Londrina State University, Londrina 86057-970, Paran\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0282-9096","authenticated-orcid":false,"given":"F\u00e1bio 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