PT  - JOURNAL ARTICLE
AU  - Alexandre G. Maganin
AU  - Guilherme R. Souza
AU  - Miriam D. Fonseca
AU  - Alexandre H. Lopes
AU  - Rafaela M. Guimarães
AU  - André Dagostin
AU  - Nerry T. Cecilio
AU  - Atlante S. Mendes
AU  - Francisco I. Gomes
AU  - Lucas M. Marques
AU  - Rangel L Silva
AU  - Leticia M. Arruda
AU  - Denis A. Santana
AU  - Henrique Lemos
AU  - Lei Huang
AU  - Marcela Davoli-Ferreira
AU  - Danielle S. Coelho
AU  - Morena B. Sant’anna
AU  - Ricardo Kusuda
AU  - Jhimmy Talbot
AU  - Gabriela Pacholczyk
AU  - Gabriela A. Buqui
AU  - Norberto P. Lopes
AU  - Jose C. Alves-Filho
AU  - Ricardo Leão
AU  - Jason C. O’Connor
AU  - Fernando Q. Cunha
AU  - Andrew Mellor
AU  - Thiago M. Cunha
TI  - Meningeal dendritic cells-astrocytes interactions elevate the kynurenine metabolic pathway to sustain neuropathic pain
AID  - 10.1101/2021.01.25.428142
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.01.25.428142
4099  - http://biorxiv.org/content/early/2021/03/10/2021.01.25.428142.short
4100  - http://biorxiv.org/content/early/2021/03/10/2021.01.25.428142.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.