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Role of CCL-2/MCP-1 produced by peripheral sensorial neurons in the development of neuropathic pain

Grant number: 18/24063-5
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): May 01, 2019
Effective date (End): August 31, 2021
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Thiago Mattar Cunha
Grantee:Atlante Silva Mendes
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID

Abstract

Neuropathic pain is a clinical condition related to direct lesion of the somatosensorial system or to diseases affecting it. Development of neuropathic pain involves changes in the characteristics of pain-signalling neurons and the immune system plays a major role in these modifications. Beyond their functions directly associated to leukocyte migration, chemokines and their receptors are expressed by multiple cell types in the nervous system, suggesting that there are roles yet to be elucidated for those pathways on neuronal cell function. The CCL-2/CCR-2 signalling pathway contributes to development and maintenance of neuropathic pain in many models of nervous system damage. Signalling through this pathway is associated to an increase in inflammatory macrophage infiltration and neuronal hyperexcitability in the Dorsal Root Ganglia (DRG), and to the neuronal-astroglial interaction in the spinal cord. However, there are still neuroimmunobiological questions that must be understood regarding the upstream/downstream signalling via CCL-2/CCR-2. Therefore, this study aims to evaluate the specific role of CCL2 produced by peripheral sensitive neurons in the development and maintenance of neuropathic pain. For that, conditional transgenic mice will be generated, in which the CCL2 gene is deleted only in sensitive neurons (Advillin-Cre/ER-CCL2Flox/Flox-RFP and Nav1.8-Cre-CCL2Flox/Flox-RFP). The mechanisms underlying signalling through CCL2 produced by sensitive neurons will also be assessed. Elucidation of these questions may contribute to the development of new and more effective therapeutic strategies for treatment of chronic pain. (AU)