Molecular Aspects Involved in the Mechanisms of Bothrops jararaca Venom-Induced Hyperalgesia: Participation of NK1 Receptor and Glial Cells

Author:

Bom Ariela de Oliveira Pedro12,Dias-Soares Monique1ORCID,Corrêa Raíssa Cristina Darroz12,Neves Camila Lima1,Hosch Natalia Gabriele3,Lucena Gabriela Gomes de1,Oliveira Camilla Garcia4,Pagano Rosana Lima5ORCID,Chacur Marucia4,Giorgi Renata1

Affiliation:

1. Laboratory of Pathophysiology, Butantan Institute, São Paulo 05503-900, SP, Brazil

2. Postgraduate Program in Toxinology, Butantan Institute, São Paulo 05503-900, SP, Brazil

3. Laboratory of Pain and Signaling, Butantan Institute, São Paulo 05503-900, SP, Brazil

4. Laboratory of Functional Neuroanatomy of Pain, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo 05508-900, SP, Brazil

5. Laboratory of Neuroscience, Hospital Sírio-Libanês, São Paulo 01308-060, SP, Brazil

Abstract

Accidents caused by Bothrops jararaca (Bj) snakes result in several local and systemic manifestations, with pain being a fundamental characteristic. The inflammatory process responsible for hyperalgesia induced by Bj venom (Bjv) has been studied; however, the specific roles played by the peripheral and central nervous systems in this phenomenon remain unclear. To clarify this, we induced hyperalgesia in rats using Bjv and collected tissues from dorsal root ganglia (DRGs) and spinal cord (SC) at 2 and 4 h post-induction. Samples were labeled for Iba-1 (macrophage and microglia), GFAP (satellite cells and astrocytes), EGR1 (neurons), and NK1 receptors. Additionally, we investigated the impact of minocycline, an inhibitor of microglia, and GR82334 antagonist on Bjv-induced hyperalgesia. Our findings reveal an increase in Iba1 in DRG at 2 h and EGR1 at 4 h. In the SC, markers for microglia, astrocytes, neurons, and NK1 receptors exhibited increased expression after 2 h, with EGR1 continuing to rise at 4 h. Minocycline and GR82334 inhibited venom-induced hyperalgesia, highlighting the crucial roles of microglia and NK1 receptors in this phenomenon. Our results suggest that the hyperalgesic effects of Bjv involve the participation of microglial and astrocytic cells, in addition to the activation of NK1 receptors.

Funder

Fundação de Amparo à Pesquisa do Estado de São Paulo

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil

Fundação Butantan

Publisher

MDPI AG

Reference76 articles.

1. Pain Modulated by Bothrops Snake Venoms: Mechanisms of Nociceptive Signaling and Therapeutic Perspectives;Almeida;Toxicon,2021

2. WHO (World Health Organization) (2024, February 28). Snakebite Envenoming. Available online: https://www.who.int/news-room/fact-sheets/detail/snakebite-envenoming#cms.

3. (2024, February 28). MINISTÉRIO DA SAÚDE (Brasil), Available online: https://bvsms.saude.gov.br/bvs/publicacoes/guia_vigilancia_saude_3ed.pdf.

4. (2024, February 28). SINAN, Available online: http://tabnet.datasus.gov.br/cgi/tabcgi.exe?sinannet/cnv/animaisbr.def%20.

5. Edema, Hyperalgesia and Myonecrosis Induced by Brazilian Bothropic Venoms: Overview of the Last Decade;Mamede;Toxicon,2020

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