• Ana C Zarpelon, Francielle C Rodrigues, Alexandre H Lopes, Guilherme R Souza, Thacyana T Carvalho, Larissa G Pinto, Damo Xu, Sergio H Ferreira, Jose C Alves-Filho, Iain B McInnes, Bernhard Ryffel, Valérie F J Quesniaux, Flora Reverchon, Stéphane Mortaud, Arnaud Menuet, Foo Y Liew, Fernando Q Cunha, Thiago M Cunha, and Waldiceu A Verri.
• *Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Parana, Brazil; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Division of Immunology, Infection and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, United Kingdom; Unités Mixtes de Recherche 7355, Centre National de la Recherche Scientifique Experimental and Molecular Immunology and Neurogenetics, Orléans, France; Immunologie et Neurogénétique Expérimentales et Moléculaires, University of Orléans, Orléans, France; and School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China.
• FASEB J. 2016 Jan 1; 30 (1): 54-65.

AbstractNeuropathic 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-α and IL-1β. IL-33-induced hyperalgesia was markedly attenuated by inhibitors of PI3K, mammalian target of rapamycin, MAPKs (p38, ERK, and JNK), NF-κB, and also by the inhibitors of glial cells (microglia and astrocytes). Furthermore, targeting these signaling pathways and cells inhibited IL-33-induced TNF-α and IL-1β production in the spinal cord. Our study, therefore, reveals an important role of oligodendrocyte-derived IL-33 in neuropathic pain.© FASEB.

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