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Role of the inflammatory immune response in the development of herpetic and post herpetic hypernociception

Grant number: 10/12309-8
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): January 01, 2011
Effective date (End): June 30, 2014
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Fernando de Queiroz Cunha
Grantee:Jaqueline Raymondi Silva
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The chronic pain is an important public health problem, affecting between 10-30% of population. Among these, there is neuropathic pain, defined by IASP as "pain initiated or caused by primary lesion or dysfunction of the nervous system." Neuropathic pain can be divided into two types: central and peripheral, depending on the site of injury of nerve tissue. Among the most common peripheral neuropathies, there is herpetic neuralgia, whose etiologic agent is the virus Varicella zoster (VZV), which is able to infect the neurons and trigger chronic neuropathic pain. Even after the disappearance of the infection in the site of injury, pain may persist, which characterizes the Post-Herpetic Neuralgia (PHN). The three main categories of neuropathic pain are observed in NPH: intermittent pain regardless of stimulus, allodynia, and stabbing pain spontaneous or evoked. Because of the ability of VZV to infected neurons and be able to survive in these cells through latency, some researchers believe that the NPH and HZ is associated to the effect of the virus on neuronal cells infected. But, recently, several studies have demonstrated that the functional changes are not just an intrinsic process of neurons, and glial cells, present in both the Central nervous system (glial cells in the spinal cord) and in the peripheral (satellite cells of dorsal root ganglion - GRD), play an important role. In this regard, it has been reported that the glial cells of the spinal cord and the DRG satellite cells contribute to the induction and maintenance of chronic pain through the release of inflammatory mediators such as IL-1², MIP-2, TNF-±, IFN-y, MCP-1, MIP-1² and PGE2 which can sensitize directly neurons. This point is important, since the antiviral immune response production of these inflammatory mediators is continuously induced by the infectious agent, which in turn is eliminated by these same mediators. Then, infection in GRDs could generate a local inflammatory process, with contribution of glial cells and immune cells that would be infiltrating GRDs. This phenomenon could be related not only with the elimination of virus in neurons, but also with the development of PHN. Our hypothesis is that the GRDs satellite cells and cells of the immune system (neutrophils, monocytes / macrophages and CD8 T lymphocytes) are responsible for creating an inflammatory environment in GRDs, in this way inducing and maintaining the nociceptive state. Thus, this project aims to study the inflammatory mechanisms involved in the development and maintenance of herpetic and post herpetic hypernociception using a murine model induced by Herpes Simplex Virus type 1. (AU)

Matéria(s) publicada(s) na Agência FAPESP sobre a bolsa:
Study explains why patients with shingles feel pain 
Articles published in other media outlets: (3 total)

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, JAQUELINE R.; LOPES, ALEXANDRE H.; TALBOT, JHIMMY; CECILIO, NERRY T.; ROSSATO, MATEUS F.; SILVA, RANGEL L.; SOUZA, GUILHERME R.; SILVA, CASSIA R.; LUCAS, GUILHERME; FONSECA, BENEDITO A.; ARRUDA, EURICO; ALVES-FILHO, JOSE C.; CUNHA, FERNANDO Q.; CUNHA, THIAGO M. Neuroimmune-Glia Interactions in the Sensory Ganglia Account for the Development of Acute Herpetic Neuralgia. JOURNAL OF NEUROSCIENCE, v. 37, n. 27, p. 6408-6422, JUL 5 2017. Web of Science Citations: 2.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SILVA, Jaqueline Raymondi. Neuro-immune interactions involved in the genesis of herpetic and postherpetic nociceptive hypersensitivity. 2014. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto Ribeirão Preto.

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