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- Title
Spinal cord oligodendrocyte-derived alarmin IL-33 mediates neuropathic pain.
- Authors
Zarpelon, Ana C.; Rodrigues, Francielle C.; Lopes, Alexandre H.; Souza, Guilherme R.; Carvalho, Thacyana T.; Pinto, Larissa G.; Damo Xu; Ferreira, Sergio H.; Alves-Filho, Jose C.; McInnes, Iain B.; Ryffel, Bernhard; Quesniaux, Valérie F. J.; Reverchon, Flora; Mortaud, Stéphane; Menuet, Arnaud; Liew, Foo Y.; Cunha, Fernando Q.; Cunha, Thiago M.; Verri Jr., Waldiceu A.
- Abstract
Neuropathic pain from injury to the peripheral and CNS represents a major health care issue. We have investigated the role of IL-33/IL-33 receptor (ST2) signaling in experimental models of neuropathic pain in mice. Chronic constriction injury (CCI) of the sciatic nerve induced IL-33 production in the spinal cord. IL-33/citrine reporter mice revealed that oligodendrocytes are the main cells expressing IL-33 within the spinal cord together with a minor expression by neurons, microglia. and astrocytes. CCI-induced mechanical hyperalgesia was reduced in IL-33R (ST2)-/- mice compared with wild-type (WT) mice. Intrathecal treatment of WT mice with soluble IL-33 receptor (IL-33 decoy receptor) markedly reduced CCI-induced hyperalgesia. Consistent with these observations, intrathecal injection of IL-33 enhanced CCI hyperalgesia and induced hyperalgesia in naive mice. IL-33-mediated hyperalgesia during CCI was dependent on a reciprocal relationship with TNF-a and IL-1β. IL-33-induced hyperalgesia was markedly attenuated by inhibitors of PI3K, mammalian target of rapamycin, MAPKs (p38, ERK, and JNK), NF-?B, and also by the inhibitors of glial cells (microglia and astrocytes). Furthermore, targeting these signaling pathways and cells inhibited IL-33-induced TNF-a and IL-1β production in the spinal cord. Our study, therefore, reveals an important role of oligodendrocyte-derived IL-33 in neuropathic pain.--Zarpelon, A. C., Rodrigues, F. C., Lopes, A. H., Souza, G. R., Carvalho, T. T., Pinto, L. G., Xu, D., Ferreira, S. H., Alves-Filho, J. C., McInnes, I. B., Ryffel, B., Quesniaux, V. F. J., Reverchon, F., Mortaud, S., Menuet, A., Liew, F. Y., Cunha, F. Q., Cunha, T. M., Verri, Jr., W. A. Spinal cord oligodendrocyte-derived alarmin IL-33 mediates neuropathic pain.
- Subjects
NEUROPATHY; SPINAL cord injuries; OLIGODENDROGLIA; INTERLEUKINS; TUMOR necrosis factors; MITOGEN-activated protein kinases; PAIN
- Publication
FASEB Journal, 2016, Vol 30, Issue 1, p54
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.14-267146