Jararhagin, a snake venom metalloproteinase, induces mechanical hyperalgesia in mice with the neuroinflammatory contribution of spinal cord microglia and astrocytes.

Abstract

Jararhagin is a hyperalgesic metalloproteinase from Bothrops jararaca venom. In rodents, jararhagin induces nociceptive behaviors that correlate with an increase in peripheral cytokine levels. However, the role of the spinal cord glia in pain processing after peripheral stimulus of jararhagin has not been investigated. Aiming to explore this proposal, mice received intraplantar (i.pl.) injection of jararhagin and the following parameters were evaluated: hyperalgesia, spinal cord TNF-α, IL-1β levels, and CX3CR1, GFAP and p-NFκB activation. The effects of intrathecal (i.t.) injection of TNF-α soluble receptor (etanercept), IL-1 receptor antagonist (IL-1Ra), and inhibitors of NFκB (PDTC), microglia (minocycline) and astrocytes (α-aminoadipate) were investigated. Jararhagin inoculation induced cytokine production (TNF-α and IL-1β) in the spinal cord, which was reduced by treatment with PDTC (40% and 50%, respectively). Jararhagin mechanical hyperalgesia and cytokine production were inhibited by treatment with etanercept (67%), IL-1Ra (60%), PDTC (70%), minocycline (60%) and α-aminoadipate (45%). Furthermore, jararhagin induced an increase in p-NFκB, CX3CR1 and GFAP detection in the spinal cord indicating activation of NFκB, microglia and astrocytes. These results demonstrate for the first time that jararhagin-induced mechanical hyperalgesia is dependent on spinal cord activation of glial cells, consequent NFκB activation, and cytokine production in mice.

• Authors: Camila R Ferraz, Thacyana T Carvalho, Victor Fattori, Telma Saraiva-Santos, Felipe A Pinho-Ribeiro, Sergio M Borghi, Marília F Manchope, Tiago H Zaninelli, Thiago M Cunha, Rubia Casagrande, Patricia B Clissa, Waldiceu A Verri Jr
• Journal: International journal of biological macromolecules (Int J Biol Macromol) Vol. 179 Pg. 610-619 (May 15 2021) ISSN: 1879-0003 [Electronic] Netherlands
• PMID: 33662422 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Crotalid Venoms
• Cytokines
• NF-kappa B
• Metalloendopeptidases
• jararhagin

Topics

• Animals
• Astrocytes (drug effects)
• Bothrops (metabolism)
• Crotalid Venoms (toxicity)
• Cytokines (metabolism)
• Hyperalgesia (chemically induced)
• Male
• Metalloendopeptidases (toxicity)
• Mice
• Mice, Inbred C57BL
• Microglia (drug effects)
• NF-kappa B (metabolism)
• Pain (chemically induced)
• Spinal Cord (drug effects)