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 H2O2 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.

Schwann cell TRPA1 mediates neuroinflammation that sustains macrophage-dependent neuropathic pain in mice / De Logu F, Nassini R, Materazzi S, Carvalho Gonçalves M, Nosi D, Rossi Degl'Innocenti D, Marone IM, Ferreira J, Li Puma S, Benemei S, Trevisan G, Souza Monteiro De Araújo D, Patacchini R, Bunnett NW, Geppetti, P.. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - ELETTRONICO. - 8:(2017), pp. 1887-1887. [10.1038/s41467-017-01739-2]

Schwann cell TRPA1 mediates neuroinflammation that sustains macrophage-dependent neuropathic pain in mice

De Logu F;Nassini R;Materazzi S;Nosi D;Rossi Degl'Innocenti D;Marone IM;FERREIRA, JULIANO;Li Puma S;Benemei S;Trevisan G;Patacchini R;Geppetti P.
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 H2O2 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.
2017
8
1887
1887
Goal 3: Good health and well-being for people
De Logu F, Nassini R, Materazzi S, Carvalho Gonçalves M, Nosi D, Rossi Degl'Innocenti D, Marone IM, Ferreira J, Li Puma S, Benemei S, Trevisan G, Sou...espandi
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1113087
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