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

Alexandre Kanashiro, Marcelo Franchin, Gabriel Shimizu Bassi, Dênis Augusto Reis Santana, Thiago Mattar Cunha, Fernando Queiróz Cunha, Luis Ulloa, Gerson Jonathan Rodrigues

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)155-162
Number of pages8
JournalFundamental and Clinical Pharmacology
Volume32
Issue number2
DOIs
StatePublished - Apr 1 2018

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Experimental Arthritis
Neutrophil Infiltration
p38 Mitogen-Activated Protein Kinases
Joints
Chemical Sympathectomy
Nadolol
Inflammation
Guanethidine
Spinal Injections
Zymosan
Receptors, Adrenergic, beta
Knee Joint
Innate Immunity
Adrenergic Receptors
Edema
Spinal Cord
Anti-Inflammatory Agents
Central Nervous System
Phosphorylation
Pharmacology

All Science Journal Classification (ASJC) codes

  • Pharmacology (medical)
  • Pharmacology

Cite this

Kanashiro, A., Franchin, M., Bassi, G. S., Reis Santana, D. A., Cunha, T. M., Cunha, F. Q., ... Rodrigues, G. J. (2018). Inhibition of spinal p38 MAPK prevents articular neutrophil infiltration in experimental arthritis via sympathetic activation. Fundamental and Clinical Pharmacology, 32(2), 155-162. https://doi.org/10.1111/fcp.12338
Kanashiro, Alexandre ; Franchin, Marcelo ; Bassi, Gabriel Shimizu ; Reis Santana, Dênis Augusto ; Cunha, Thiago Mattar ; Cunha, Fernando Queiróz ; Ulloa, Luis ; Rodrigues, Gerson Jonathan. / Inhibition of spinal p38 MAPK prevents articular neutrophil infiltration in experimental arthritis via sympathetic activation. In: Fundamental and Clinical Pharmacology. 2018 ; Vol. 32, No. 2. pp. 155-162.
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Inhibition of spinal p38 MAPK prevents articular neutrophil infiltration in experimental arthritis via sympathetic activation. / Kanashiro, Alexandre; Franchin, Marcelo; Bassi, Gabriel Shimizu; Reis Santana, Dênis Augusto; Cunha, Thiago Mattar; Cunha, Fernando Queiróz; Ulloa, Luis; Rodrigues, Gerson Jonathan.

In: Fundamental and Clinical Pharmacology, Vol. 32, No. 2, 01.04.2018, p. 155-162.

Research output: Contribution to journalArticle

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