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Schwann cell TRPA1 mediates neuroinflammation that sustains macrophage-dependent neuropathic pain in mice.
- Source :
-
Nature communications [Nat Commun] 2017 Dec 01; Vol. 8 (1), pp. 1887. Date of Electronic Publication: 2017 Dec 01. - Publication Year :
- 2017
-
Abstract
- It is known that transient receptor potential ankyrin 1 (TRPA1) channels, expressed by nociceptors, contribute to neuropathic pain. Here we show that TRPA1 is also expressed in Schwann cells. We found that in mice with partial sciatic nerve ligation, TRPA1 silencing in nociceptors attenuated mechanical allodynia, without affecting macrophage infiltration and oxidative stress, whereas TRPA1 silencing in Schwann cells reduced both allodynia and neuroinflammation. Activation of Schwann cell TRPA1 evoked NADPH oxidase 1 (NOX1)-dependent H <subscript>2</subscript> O <subscript>2</subscript> release, and silencing or blocking Schwann cell NOX1 attenuated nerve injury-induced macrophage infiltration, oxidative stress and allodynia. Furthermore, the NOX2-dependent oxidative burst, produced by macrophages recruited to the perineural space activated the TRPA1-NOX1 pathway in Schwann cells, but not TRPA1 in nociceptors. Schwann cell TRPA1 generates a spatially constrained gradient of oxidative stress, which maintains macrophage infiltration to the injured nerve, and sends paracrine signals to activate TRPA1 of ensheathed nociceptors to sustain mechanical allodynia.
- Subjects :
- Animals
Humans
Male
Mice
Mice, Inbred C57BL
NADPH Oxidase 1 genetics
NADPH Oxidase 1 immunology
NADPH Oxidase 2 genetics
NADPH Oxidase 2 immunology
Neuralgia genetics
Oxidative Stress
Sciatic Nerve immunology
TRPA1 Cation Channel genetics
Macrophages immunology
Neuralgia immunology
Schwann Cells immunology
TRPA1 Cation Channel immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 8
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 29192190
- Full Text :
- https://doi.org/10.1038/s41467-017-01739-2