Peripheral mechanisms involved in Tityus bahiensis venom-induced pain

• Published in: Toxicon (Oxford) Vol. 200; pp. 3 - 12
• Main Authors: Ferraz, Camila R., Manchope, Marília F., Andrade, Ketlem C., Saraiva-Santos, Telma, Franciosi, Anelise, Zaninelli, Tiago H., Bagatim-Souza, Julia, Borghi, Sergio M., Cândido, Denise M., Knysak, Irene, Casagrande, Rubia, Kwasniewski, Fábio H., Verri, Waldiceu A.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01-09-2021
• Subjects: Cytokines; Hyperalgesia; NFκB; Pain; Tityus bahiensis; Pain; Cytokines; NFκB; Tityus bahiensis; Hyperalgesia
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/j.toxicon.2021.06.013

Scorpionism is a public health burden in Brazil. Tityus bahiensis is responsible for most accidents in the Southeastern region of Brazil. Here, the hyperalgesic mechanisms of Tityus bahiensis venom were investigated, focusing on the role of pro-inflammatory cytokines (tumor necrosis factor alpha [TNF-α] and interleukin 1 beta [IL-1β]) and activation of the transcription factor NFκB. Intraplantar (i.pl.) administration of Tityus bahiensis venom (0.2, 0.6, 1.2 and 2.4 μg/20 μL i.pl.) induced mechanical hyperalgesia and thermal hyperalgesia. The 2.4 μg dose of Tityus bahiensis venom induced overt pain-like behavior and increased myeloperoxidase (MPO) and N-acetyl-beta-D-glucosaminidase (NAG) activities, TNF-α and IL-1β levels in the paw tissue. Systemic pre-treatment with etanercept (soluble TNF-α receptor; 10 mg/kg), IL-1ra (IL-1 receptor antagonist; 30 mg/kg) and pyrrolidine dithiocarbamate (PDTC, nuclear factor kappa B [NFκB] inhibitor; 100 mg/kg) inhibited Tityus bahiensis venom-induced mechanical and thermal hyperalgesia, MPO and NAG activity and overt pain-like behavior. These data demonstrate the involvement of TNF-α and IL-1β signaling as well as NFκB activation in Tityus bahiensis venom-induced mechanical and thermal hyperalgesia, overt pain-like behavior, and MPO activity and NAG activity, indicating thus, that targeting these mechanisms might contribute to reducing the pain in this scorpionism.
•Tityus bahiensis venom increased tumor necrosis factor α (TNF-α) and interleukin 1 β (IL-1β) levels in the paw tissue.•Treatment with inhibitors of TNF-α, IL-1β and nuclear factor kappa B (NFκB) reduced Tityus bahiensis venom-induced pain.•Those treatments also reduced Tityus bahiensis venom-induced myeloperoxidase and N-acetyl-beta-D-glucosaminidase activities.•This is the first demonstration of TNF-α, IL-1β and NFκB contribution to Tityus bahiensis venom-induced pain.