Janus kinase 2 activation participates in prostaglandin E2-induced hyperalgesia

Autor: Elayne Vieira Dias, André Schwambach Vieira, Dionéia Araldi, Filipe César do Prado, Carlos Amílcar Parada, Cláudia Herrera Tambeli
Přispěvatelé: UNIVERSIDADE ESTADUAL DE CAMPINAS
Rok vydání: 2016
Předmět:
Zdroj: Repositório Institucional da Unicamp
Universidade Estadual de Campinas (UNICAMP)
instacron:UNICAMP
Repositório da Produção Científica e Intelectual da Unicamp
ISSN: 0024-3205
DOI: 10.1016/j.lfs.2016.10.001
Popis: Agradecimentos: This work was supported by Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior - CAPES and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (Grant Number 140621/2008-3) - CNPq/Brazil Abstract: Prostaglandin E2 (PGE2) is one of the major signaling molecules involved in hyperalgesia, acting directly on nociceptors and resulting in the activation of PKA and PKC. Once active, these kinases phosphorylate many cellular proteins, resulting in changes on nociceptors sensorial transduction properties. The Janus Kinases (JAKs) are a family of intracellular signaling molecules generally associated with cytokine signaling, and their activity can be increased in nociceptors after peripheral inflammation. However, there are no evidences of JAKs direct involvement in PGE2 mediated sensitization of nociceptors. Therefore, the aim of the present study was to explore a possible role for JAKs in PGE2 mediated sensitization. In cultured dorsal root ganglion (DRG) neurons, we observed that the administration of PGE2 increases capsaicin induced calcium transients, and a pre-incubation of DRG cells with the JAK inhibitor AG490 blocks this PGE2 in vitro effect. Intrathecal administration of AG490 to ten-weeks old male Wistar rats reduces the hyperalgesia induced by the intraplantar administration of PGE2 or carrageenan in the right hind paw. We also observed that carrageenan administration in the right hind paw induced an increase in membrane associated PKCepsilon in the ipsilateral L5 DRG, and this increase was blocked by intrathecal AG490 administration. In conclusion the present study indicates that the JAKs expressed in the DRG and spinal cord may have a role in the sensitization of nociceptors by a peripheral inflammatory event. Moreover, the inhibition of JAKs may be a possible novel pharmacological target for the control of the inflammatory hyperalgesia COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ Fechado
Databáze: OpenAIRE
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