Spinal cord oligodendrocyte-derived alarmin IL-33 mediates neuropathic pain

Author(s):Show less -

Zarpelon, Ana C. ^[1] ; Rodrigues, Francielle C. ^[1] ; Lopes, Alexandre H. ^[2] ; Souza, Guilherme R. ^[2] ; Carvalho, Thacyana T. ^[1] ; Pinto, Larissa G. ^[2] ; Xu, Damo ^[3] ; Ferreira, Sergio H. ^[2] ; Alves-Filho, Jose C. ^[2] ; McInnes, Iain B. ^[3] ; Ryffel, Bernhard ^{[4, 5]} ; Quesniaux, Valerie F. J. ^{[4, 5]} ; Reverchon, Flora ^{[4, 5]} ; Mortaud, Stephane ^{[4, 5]} ; Menuet, Arnaud ^{[4, 5]} ; Liew, Foo Y. ^{[3, 6]} ; Cunha, Fernando Q. ^[2] ; Cunha, Thiago M. ^[2] ; Verri, Jr., Waldiceu A. ^[1]

Affiliation

^[1] Univ Estadual Londrina, Ctr Ciencias Biol, Dept Ciencias Patol, BR-86057970 Londrina, Parana - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Sao Paulo - Brazil

^[3] Univ Glasgow, Glasgow Biomed Res Ctr, Div Immunol Infect & Inflammat, Glasgow, Lanark - Scotland

^[4] Ctr Natl Rech Sci Expt & Mol Immunol & Neurogenet, Unites Mixtes Rech 7355, Orleans - France

^[5] Univ Orleans, Immunol & Neurogenet Expt & Mol, Orleans - France

^[6] Soochow Univ, Sch Biol & Basic Med Sci, Suzhou - Peoples R China

• Document type: Journal article
• Source: FASEB JOURNAL; v. 30, n. 1, p. 54-65, JAN 2016.
• Web of Science Citations: 50

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-alpha and IL-1 beta. IL-33-induced hyperalgesia was markedly attenuated by inhibitors of PI3K, mammalian target of rapamycin, MAPKs (p38, ERK, and JNK), NF-kappa B, and also by the inhibitors of glial cells (microglia and astrocytes). Furthermore, targeting these signaling pathways and cells inhibited IL-33-induced TNF-alpha a and IL-1 beta 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. FASEB J. 30, 54-65 (2016). www.fasebj.org (AU)

• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 11/19670-0 - Mechanisms involved in the pathophysiology of rheumatoid arthritis, pain and sepsis
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Projects - Thematic Grants