Advanced search
Start date
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

Full text
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]
Total Authors: 19
[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
Total Affiliations: 6
Document type: Journal article
Source: FASEB JOURNAL; v. 30, n. 1, p. 54-65, JAN 2016.
Web of Science Citations: 51

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). (AU)

FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
Grantee:Fernando de Queiroz Cunha
Support type: 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 type: Research Projects - Thematic Grants