| Autor: |
Guilherme R. Souza, Fernando Q. Cunha, Miriam D. Fonseca, Alexandre H. Lopes, Morena Brazil Sant'Anna, Rangel L. Silva, Gabriela A. Buqui, Jhimmy Talbot, Jason C. O’Connor, Thiago M. Cunha, Rafaela M. Guimarães, Dênis Augusto Reis Santana, Alexandre Gomes de Macedo Maganin, Norberto P. Lopes, Ricardo M. Leão, Atlante S. Mendes, Nerry T. Cecilio, Andre Dagostin, Gabriela Pacholczyk, Letícia Magalhães Arruda, Danielle S. Coelho, Marcela Davoli-Ferreira, Henrique Lemos, Lei Huang, Ricardo Kusuda, José C. Alves-Filho, Lucas Miranda Marques, Andrew L. Mellor, Francisco Isaac Fernandes Gomes |
| Rok vydání: |
2021 |
| Předmět: |
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| Popis: |
Neuropathic pain is triggered by injury to the somatosensory system, and is one of the most important types of chronic pain. Nevertheless, critical pathophysiological mechanisms that maintain neuropathic pain are poorly understood. Here, we show that neuropathic pain is abrogated when the kynurenine metabolic pathway (KYNPATH) initiated by the enzyme indoleamine 2,3-dioxygenase (IDO) is ablated pharmacologically or genetically. Mechanistically, it was found that IDO upregulation in dendritic cells that accumulate in the dorsal root leptomeninges led to increased levels of kynurenine (Kyn) in the spinal cord, where Kyn is metabolized by astrocytes-expressed kynurenine-3-monooxygenase into a pro-nociceptive metabolite 3-hydroxykynurenine. In conclusion, these data reveal a novel role for KYNPATH as an important factor maintaining neuropathic pain during neuroimmune-glia cells interactions. This novel paradigm offers potential new targets for drug development against this type of chronic pain. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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