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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Spinal GABA-B receptor modulates neutrophil recruitment to the knee joint in zymosan-induced arthritis

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Author(s):
Bassi, Gabriel S. [1] ; Malvar, David do C. [2] ; Cunha, Thiago M. [3] ; Cunha, Fernando Q. [3] ; Kanashiro, Alexandre [3]
Total Authors: 5
Affiliation:
[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil
[2] Univ Fed Rural Rio de Janeiro, Dept Pharmaceut Sci, BR 465, Km 07, BR-23890000 Seropedica, RJ - Brazil
[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY; v. 389, n. 8, p. 851-861, AUG 2016.
Web of Science Citations: 3
Abstract

Recent studies have demonstrated that the central nervous system controls inflammatory responses by activating complex efferent neuroimmune pathways. The present study was designed to evaluate the role that central gamma-aminobutyric acid type B (GABA-B) receptor plays in neutrophil migration in a murine model of zymosan-induced arthritis by using different pharmacological tools. We observed that intrathecal administration of baclofen, a selective GABA-B agonist, exacerbated the inflammatory response in the knee after zymosan administration characterized by an increase in the neutrophil recruitment and knee joint edema, whereas saclofen, a GABA-B antagonist, exerted the opposite effect. Intrathecal pretreatment of the animals with SB203580 (an inhibitor of p38 mitogen-activated protein kinase) blocked the pro-inflammatory effect of baclofen. On the other hand, systemic administration of guanethidine, a sympatholytic drug that inhibits catecholamine release, and nadolol, a beta-adrenergic receptor antagonist, reversed the effect of saclofen. Moreover, saclofen suppressed the release of the pro-inflammatory cytokines into the knee joint (ELISA) and pain-related behaviors (open field test). Since the anti-inflammatory effect of saclofen depends on the sympathetic nervous system integrity, we observed that isoproterenol, a beta-adrenergic receptor agonist, mimics the central GABA-B blockade decreasing knee joint neutrophil recruitment. Together, these results demonstrate that the pharmacological manipulation of spinal GABAergic transmission aids control of neutrophil migration to the inflamed joint by modulating the activation of the knee joint-innervating sympathetic terminal fibers through a mechanism dependent on peripheral beta-adrenergic receptors and central components, such as p38 MAPK. (AU)

FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
Grantee:Fernando de Queiroz Cunha
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 12/04237-2 - Antiinflammatory Cholinergic Pathway: The role of neuroimmunomodulation in the control of inflammatory response.
Grantee:Alexandre Kanashiro
Support Opportunities: Scholarships in Brazil - Young Researchers
FAPESP's process: 11/19670-0 - Mechanisms involved in the pathophysiology of rheumatoid arthritis, pain and sepsis
Grantee:Fernando de Queiroz Cunha
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 11/20343-4 - Antiinflammatory cholinergic pathway: the role of neuroimmunomodulation in the control of inflammatory response
Grantee:Alexandre Kanashiro
Support Opportunities: Research Grants - Young Investigators Grants