<i>Tityus serrulatus</i> Scorpion Venom-Induced Nociceptive Responses Depend on TRPV1, Immune Cells, and Pro-Inflammatory Cytokines
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...
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2025-06-01
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| author | Camila R. Ferraz Marília F. Manchope Mariana M. Bertozzi Telma Saraiva-Santos Ketlem C. Andrade Anelise Franciosi Tiago H. Zaninelli Julia Bagatim-Souza Sergio M. Borghi Denise M. Cândido Thiago M. Cunha Rubia Casagrande Fábio H. Kwasniewski Waldiceu A. Verri |
| author_facet | Camila R. Ferraz Marília F. Manchope Mariana M. Bertozzi Telma Saraiva-Santos Ketlem C. Andrade Anelise Franciosi Tiago H. Zaninelli Julia Bagatim-Souza Sergio M. Borghi Denise M. Cândido Thiago M. Cunha Rubia Casagrande Fábio H. Kwasniewski Waldiceu A. Verri |
| author_sort | Camila R. Ferraz |
| collection | DOAJ |
| description | 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 <i>Tityus serrulatus</i> venom induces hyperalgesia in mice. Through behavioral, immune, imaging assays, and mice genetics, we demonstrate evidence of neuroimmune crosstalk during scorpion stings. <i>Tityus serrulatus</i> 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-α and IL-1β. Blocking TRPV1<sup>+</sup> neurons, TNF-α, IL-1β, and NFκB reduced the mechanical and thermal hyperalgesia, overt pain-like behavior, and the migration of macrophages and neutrophils induced by <i>Tityus serrulatus</i> venom. Collectively, <i>Tityus serrulatus</i> venom targets primary afferent nociceptive TRPV1<sup>+</sup> neurons to induce hyperalgesia through the recruitment of macrophages and neutrophils and the release of pro-inflammatory cytokines. |
| format | Article |
| id | doaj-art-b979815f962c4e12baa0f054201b2ead |
| institution | Kabale University |
| issn | 2072-6651 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj-art-b979815f962c4e12baa0f054201b2ead2025-08-20T03:32:28ZengMDPI AGToxins2072-66512025-06-0117733210.3390/toxins17070332<i>Tityus serrulatus</i> Scorpion Venom-Induced Nociceptive Responses Depend on TRPV1, Immune Cells, and Pro-Inflammatory CytokinesCamila R. Ferraz0Marília F. Manchope1Mariana M. Bertozzi2Telma Saraiva-Santos3Ketlem C. Andrade4Anelise Franciosi5Tiago H. Zaninelli6Julia Bagatim-Souza7Sergio M. Borghi8Denise M. Cândido9Thiago M. Cunha10Rubia Casagrande11Fábio H. Kwasniewski12Waldiceu A. Verri13Department of Immunology, Parasitology and General Pathology, Londrina State University, Londrina 86057-970, Paraná, BrazilDepartment of Immunology, Parasitology and General Pathology, Londrina State University, Londrina 86057-970, Paraná, BrazilDepartment of Immunology, Parasitology and General Pathology, Londrina State University, Londrina 86057-970, Paraná, BrazilDepartment of Immunology, Parasitology and General Pathology, Londrina State University, Londrina 86057-970, Paraná, BrazilDepartment of Immunology, Parasitology and General Pathology, Londrina State University, Londrina 86057-970, Paraná, BrazilDepartment of Immunology, Parasitology and General Pathology, Londrina State University, Londrina 86057-970, Paraná, BrazilDepartment of Immunology, Parasitology and General Pathology, Londrina State University, Londrina 86057-970, Paraná, BrazilDepartment of Immunology, Parasitology and General Pathology, Londrina State University, Londrina 86057-970, Paraná, BrazilDepartment of Immunology, Parasitology and General Pathology, Londrina State University, Londrina 86057-970, Paraná, BrazilArthropod Laboratory, Butantan Institute, São Paulo 05503-900, São Paulo, BrazilCenter of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, São Paulo, BrazilDepartment of Pharmaceutical Sciences, Centre of Health Sciences, Londrina State University, Londrina 86057-970, Paraná, BrazilDepartment of Immunology, Parasitology and General Pathology, Londrina State University, Londrina 86057-970, Paraná, BrazilDepartment of Immunology, Parasitology and General Pathology, Londrina State University, Londrina 86057-970, Paraná, BrazilFor 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 <i>Tityus serrulatus</i> venom induces hyperalgesia in mice. Through behavioral, immune, imaging assays, and mice genetics, we demonstrate evidence of neuroimmune crosstalk during scorpion stings. <i>Tityus serrulatus</i> 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-α and IL-1β. Blocking TRPV1<sup>+</sup> neurons, TNF-α, IL-1β, and NFκB reduced the mechanical and thermal hyperalgesia, overt pain-like behavior, and the migration of macrophages and neutrophils induced by <i>Tityus serrulatus</i> venom. Collectively, <i>Tityus serrulatus</i> venom targets primary afferent nociceptive TRPV1<sup>+</sup> neurons to induce hyperalgesia through the recruitment of macrophages and neutrophils and the release of pro-inflammatory cytokines.https://www.mdpi.com/2072-6651/17/7/332<i>Tityus serrulatus</i>hyperalgesiapainneuroinflammationTNF-αIL-1β |
| spellingShingle | Camila R. Ferraz Marília F. Manchope Mariana M. Bertozzi Telma Saraiva-Santos Ketlem C. Andrade Anelise Franciosi Tiago H. Zaninelli Julia Bagatim-Souza Sergio M. Borghi Denise M. Cândido Thiago M. Cunha Rubia Casagrande Fábio H. Kwasniewski Waldiceu A. Verri <i>Tityus serrulatus</i> Scorpion Venom-Induced Nociceptive Responses Depend on TRPV1, Immune Cells, and Pro-Inflammatory Cytokines Toxins <i>Tityus serrulatus</i> hyperalgesia pain neuroinflammation TNF-α IL-1β |
| title | <i>Tityus serrulatus</i> Scorpion Venom-Induced Nociceptive Responses Depend on TRPV1, Immune Cells, and Pro-Inflammatory Cytokines |
| title_full | <i>Tityus serrulatus</i> Scorpion Venom-Induced Nociceptive Responses Depend on TRPV1, Immune Cells, and Pro-Inflammatory Cytokines |
| title_fullStr | <i>Tityus serrulatus</i> Scorpion Venom-Induced Nociceptive Responses Depend on TRPV1, Immune Cells, and Pro-Inflammatory Cytokines |
| title_full_unstemmed | <i>Tityus serrulatus</i> Scorpion Venom-Induced Nociceptive Responses Depend on TRPV1, Immune Cells, and Pro-Inflammatory Cytokines |
| title_short | <i>Tityus serrulatus</i> Scorpion Venom-Induced Nociceptive Responses Depend on TRPV1, Immune Cells, and Pro-Inflammatory Cytokines |
| title_sort | i tityus serrulatus i scorpion venom induced nociceptive responses depend on trpv1 immune cells and pro inflammatory cytokines |
| topic | <i>Tityus serrulatus</i> hyperalgesia pain neuroinflammation TNF-α IL-1β |
| url | https://www.mdpi.com/2072-6651/17/7/332 |
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