Premium
Inhibition of spinal p38 MAPK prevents articular neutrophil infiltration in experimental arthritis via sympathetic activation
Author(s) -
Kanashiro Alexandre,
Franchin Marcelo,
Bassi Gabriel Shimizu,
Reis Santana Dênis Augusto,
Cunha Thiago Mattar,
Cunha Fernando Queiróz,
Ulloa Luis,
Rodrigues Gerson Jonathan
Publication year - 2018
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12338
Subject(s) - medicine , inflammation , mapk/erk pathway , p38 mitogen activated protein kinases , arthritis , zymosan , stimulation , spinal cord , protein kinase a , pharmacology , anesthesia , immunology , endocrinology , kinase , chemistry , biology , microbiology and biotechnology , biochemistry , psychiatry , in vitro
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.