Neuroimmune–Glia Interactions in the Sensory Ganglia Account for the Development of Acute Herpetic Neuralgia
| Autor: | Cássia Regina Silva, Rangel L. Silva, Jaqueline Raymondi Silva, Jhimmy Talbot, Fernando Q. Cunha, Guilherme R. Souza, Eurico Arruda, José C. Alves-Filho, Thiago M. Cunha, Guilherme de Araújo Lucas, Benedito Antonio Lopes da Fonseca, Mateus Fortes Rossato, Nerry T. Cecilio, Alexandre H. Lopes |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Pathology medicine.medical_specialty Sensory Receptor Cells Neuroimmunomodulation Neuralgia Postherpetic Mice Transgenic Inflammation Sensory system medicine.disease_cause Mice 03 medical and health sciences 0302 clinical medicine Ganglia Sensory Downregulation and upregulation Leukocytes medicine Animals DOR HERPETIC NEURALGIA Research Articles Cells Cultured business.industry General Neuroscience Pathophysiology nervous system diseases Mice Inbred C57BL body regions 030104 developmental biology Herpes simplex virus Murine model Disease Progression Tumor necrosis factor alpha medicine.symptom business Neuroglia 030217 neurology & neurosurgery |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.2233-16.2017 |
| Popis: | Herpetic neuralgia is the most important symptom of herpes zoster disease, which is caused by Varicella zoster. Nevertheless, the pathophysiological mechanisms involved in herpetic neuralgia are not totally elucidated. Here, we examined the neuroimmune interactions at the sensory ganglia that account for the genesis of herpetic neuralgia using a murine model of Herpes Simplex Virus Type-1 (HSV-1) infection. The cutaneous HSV-1 infection of mice results in the development of a zosteriform-like skin lesion followed by a time-dependent increase in pain-like responses (mechanical allodynia). Leukocytes composed mainly of macrophages and neutrophils infiltrate infected DRGs and account for the development of herpetic neuralgia. Infiltrating leukocytes are responsible for driving the production of TNF, which in turn mediates the development of herpetic neuralgia through downregulation of the inwardly rectifying K(+) channel Kir4.1 in satellite glial cells. These results revealed that neuroimmune–glia interactions at the sensory ganglia play a critical role in the genesis of herpetic neuralgia. In conclusion, the present study elucidates novel mechanisms involved in the genesis of acute herpetic pain and open new avenues for its control. SIGNIFICANCE STATEMENT Acute herpetic neuralgia is the most important symptom of herpes zoster disease and it is very difficult to treat. Using a model of peripheral infection of mice with HSV-1, we have characterized for the first time the neuroimmune–glia interactions in the sensory ganglia that account for the development of acute herpetic neuralgia. Among these mechanisms, leukocytes composed mainly of macrophages and neutrophils infiltrate infected sensory ganglia and are responsible for driving the production of TNF. TNF, via TNFR1, mediates herpetic neuralgia development through downregulation of the inwardly rectifying K(+) channel Kir4.1 in satellite glial cells. This study elucidates novel mechanisms involved in the genesis of acute herpetic neuralgia and open new avenues for its control. |
| Databáze: | OpenAIRE |
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