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Modulation of spinal glial cells during the reversion of neuropathic pain induced by cortical stimulation

Grant number: 12/11925-2
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2012
Effective date (End): July 31, 2013
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Rosana de Lima Pagano
Grantee:Guilherme Diogo Silva
Host Institution: Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil


Considering the unsatisfactory results of current pharmacological management, the electrical stimulation of the motor cortex (MCS) appeared as a remarkably effective therapy for the treatment of neuropathic pain; however, exist refractory patients to the effects of this method. The elucidation of the exact mechanism of action could corroborate to understanding and overcoming the limitations of MCS. Astrocytes and microglial cells are responsible for the induction and maintenance of the phenomenon of neuropathic pain in both morphological and functional levels, due to an interface between the nervous system and immune system. This phenomenon is mediated, for example, by tumor necrosis factor-± (TNF-±) and interleukin-1² (IL-1²), which regulate the neuroinflammation associated peripheral neuropathy. It has been demonstrated by our group that the MCS reverses neuropathic pain in rats with chronic constriction of the sciatic nerve. From this perspective, understanding the pattern of activation of glial cells, with consequent modulation of algogenic cytokine release, are topics of major relevance. Thus, in this project, animals with peripheral neuropathy, stimulated or not, will be assessed in the paw pressure test and then will determine the activation pattern of astrocytes (GFAP) and microglia (OX-42) spinal, concurrently with the labeling for TNF-± and IL-1² and for P2X4 receptor (microglial activation marker) by immunohistochemical assay. Also, it will be evaluated the involvement of the endocannabinoid system by immunolabeling for cannabinoid receptor of type 1 and 2, which mediates the inhibition of neuropathic pain. Therefore, understanding how these factors are modulated after cortical stimulation would allow an in depth understanding of this technique and, possibly, improved the method for greater clinic coverage. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SILVA, GUILHERME D.; LOPES, PATRICIA S. S.; FONOFF, ERICH T.; PAGANO, ROSANA L.. The spinal anti-inflammatory mechanism of motor cortex stimulation: cause of success and refractoriness in neuropathic pain?. JOURNAL OF NEUROINFLAMMATION, v. 12, . (09/50772-4, 12/11925-2)

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