Inhibition of spinal p38 MAPK prevents articular neutrophil infiltration in experimental arthritis via sympathetic activation.

Journal Article (Journal Article)

The central nervous system controls the innate immunity by modulating efferent neuronal networks. Recently, we have reported that central brain stimulation inhibits inflammatory responses. In the present study, we investigate whether spinal p38 mitogen-activated protein kinase (MAPK) affects joint inflammation in experimental arthritis. Firstly, we observed that intra-articular administration of zymosan in mice induces the phosphorylation of the spinal cord p38 MAPK. In addition, we demonstrated that spinal p38 MAPK inhibition with intrathecal injection of SB203580, a conventional and well-characterized inhibitor, prevents knee joint neutrophil recruitment, edema formation, experimental score and cytokine production. This local anti-inflammatory effect was completely abolished with chemical sympathectomy (guanethidine) and beta-adrenergic receptors blockade (nadolol). In conclusion, our results suggest that pharmacological strategies involving the modulation of spinal p38 MAPK circuit can prevent joint inflammation via sympathetic networks and beta-adrenoceptors activation.

Full Text

Duke Authors

Cited Authors

  • Kanashiro, A; Franchin, M; Bassi, GS; Reis Santana, DA; Cunha, TM; Cunha, FQ; Ulloa, L; Rodrigues, GJ

Published Date

  • April 2018

Published In

Volume / Issue

  • 32 / 2

Start / End Page

  • 155 - 162

PubMed ID

  • 29206314

Pubmed Central ID

  • PMC6262227

Electronic International Standard Serial Number (EISSN)

  • 1472-8206

Digital Object Identifier (DOI)

  • 10.1111/fcp.12338


  • eng

Conference Location

  • England