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Article

Tityus serrulatus Scorpion Venom-Induced Nociceptive Responses Depend on TRPV1, Immune Cells, and Pro-Inflammatory Cytokines

by
Camila R. Ferraz
1,
Marília F. Manchope
1,
Mariana M. Bertozzi
1,
Telma Saraiva-Santos
1,
Ketlem C. Andrade
1,
Anelise Franciosi
1,
Tiago H. Zaninelli
1,
Julia Bagatim-Souza
1,
Sergio M. Borghi
1,2,
Denise M. Cândido
3,
Thiago M. Cunha
4,5,
Rubia Casagrande
6,
Fábio H. Kwasniewski
1 and
Waldiceu A. Verri
1,*
1
Department of Immunology, Parasitology and General Pathology, Londrina State University, Londrina 86057-970, Paraná, Brazil
2
Center for Research in Health Sciences, University of Northern Paraná, Londrina 86057-970, Paraná, Brazil
3
Arthropod Laboratory, Butantan Institute, São Paulo 05503-900, São Paulo, Brazil
4
Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, São Paulo, Brazil
5
Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, São Paulo, Brazil
6
Department of Pharmaceutical Sciences, Centre of Health Sciences, Londrina State University, Londrina 86057-970, Paraná, Brazil
*
Author to whom correspondence should be addressed.
Toxins 2025, 17(7), 332; https://doi.org/10.3390/toxins17070332
Submission received: 31 May 2025 / Revised: 26 June 2025 / Accepted: 28 June 2025 / Published: 30 June 2025
(This article belongs to the Section Animal Venoms)
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Abstract

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-α and IL-1β. Blocking TRPV1+ 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 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.
Keywords: Tityus serrulatus; hyperalgesia; pain; neuroinflammation; TNF-α; IL-1β; NFκB Tityus serrulatus; hyperalgesia; pain; neuroinflammation; TNF-α; IL-1β; NFκB

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MDPI and ACS Style

Ferraz, C.R.; Manchope, M.F.; Bertozzi, M.M.; Saraiva-Santos, T.; Andrade, K.C.; Franciosi, A.; Zaninelli, T.H.; Bagatim-Souza, J.; Borghi, S.M.; Cândido, D.M.; et al. Tityus serrulatus Scorpion Venom-Induced Nociceptive Responses Depend on TRPV1, Immune Cells, and Pro-Inflammatory Cytokines. Toxins 2025, 17, 332. https://doi.org/10.3390/toxins17070332

AMA Style

Ferraz CR, Manchope MF, Bertozzi MM, Saraiva-Santos T, Andrade KC, Franciosi A, Zaninelli TH, Bagatim-Souza J, Borghi SM, Cândido DM, et al. Tityus serrulatus Scorpion Venom-Induced Nociceptive Responses Depend on TRPV1, Immune Cells, and Pro-Inflammatory Cytokines. Toxins. 2025; 17(7):332. https://doi.org/10.3390/toxins17070332

Chicago/Turabian Style

Ferraz, Camila R., 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, and et al. 2025. "Tityus serrulatus Scorpion Venom-Induced Nociceptive Responses Depend on TRPV1, Immune Cells, and Pro-Inflammatory Cytokines" Toxins 17, no. 7: 332. https://doi.org/10.3390/toxins17070332

APA Style

Ferraz, C. R., Manchope, M. F., Bertozzi, M. M., Saraiva-Santos, T., Andrade, K. C., Franciosi, A., Zaninelli, T. H., Bagatim-Souza, J., Borghi, S. M., Cândido, D. M., Cunha, T. M., Casagrande, R., Kwasniewski, F. H., & Verri, W. A. (2025). Tityus serrulatus Scorpion Venom-Induced Nociceptive Responses Depend on TRPV1, Immune Cells, and Pro-Inflammatory Cytokines. Toxins, 17(7), 332. https://doi.org/10.3390/toxins17070332

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