Peripheral Brain Derived Neurotrophic Factor Precursor Regulates Pain as an Inflammatory Mediator

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dc.contributor.authorLuo, C.
dc.contributor.authorZhong, X.-L.
dc.contributor.authorZhou, F.H.
dc.contributor.authorLi, J.-Y.
dc.contributor.authorZhou, P.
dc.contributor.authorXu, J.-M.
dc.contributor.authorSong, B.
dc.contributor.authorLi, C.-Q.
dc.contributor.authorZhou, X.-F.
dc.contributor.authorDai, R.-P.
dc.date.issued2016
dc.description.abstractThe precursor of brain derived neurotrophic factor (proBDNF), the unprocessed BDNF gene product, binds to its receptors and exerts the opposing biologic functions of mature BDNF. proBDNF is expressed in the peripheral tissues but the functions of peripheral proBDNF remain elusive. Here we showed that proBDNF and its predominant receptor, p75 pan-neurotrophin receptor were upregulated in the nerve fibers and inflammatory cells in the local tissue in inflammatory pain. Neutralization of proBDNF by polyclonal antibody attenuated pain in different models of inflammatory pain. Unilateral intraplantar supplementation of proBDNF by injecting exogenous proBDNF or ectopic overexpression resulted in pain hypersensitivity and induced spinal phosphorylated extracellular signal-regulated kinase activation. Exogenous proBDNF injection induced the infiltration of inflammatory cells and the activation of proinflammatory cytokines, suggesting that inflammatory reaction contributed to the pro-algesic effect of proBDNF. Finally, we generated monoclonal anti-proBDNF antibody that could biologically block proBDNF. Administration of monoclonal Ab-proBDNF attenuated various types of inflammatory pain and surgical pain. Thus, peripheral proBDNF is a potential pain mediator and antiproBDNF pretreatment may alleviate the development of inflammatory pain.
dc.description.statementofresponsibilityCong Luo, Xiao-Lin Zhong, Fiona H. Zhou, Jia-yi Li, Pei Zhou, Jun-Mei Xu, Bo Song, Chang-Qi Li, Xin-Fu Zhou and Ru-Ping Dai
dc.identifier.citationScientific Reports, 2016; 6(1):27171-1-27171-11
dc.identifier.doi10.1038/srep27171
dc.identifier.issn2045-2322
dc.identifier.issn2045-2322
dc.identifier.orcidZhou, F.H. [0000-0003-3113-1671]
dc.identifier.urihttps://hdl.handle.net/2440/133548
dc.language.isoen
dc.publisherNature
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/595937
dc.rights© 2016, The Author(s) This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
dc.source.urihttps://doi.org/10.1038/srep27171
dc.subjectNeurotrophic factors
dc.subjectSensory processing
dc.subject.meshCells, Cultured
dc.subject.meshAnimals
dc.subject.meshHumans
dc.subject.meshMice
dc.subject.meshRats
dc.subject.meshPain
dc.subject.meshDisease Models, Animal
dc.subject.meshExtracellular Signal-Regulated MAP Kinases
dc.subject.meshBrain-Derived Neurotrophic Factor
dc.subject.meshReceptors, Nerve Growth Factor
dc.subject.meshNerve Tissue Proteins
dc.subject.meshInflammation Mediators
dc.subject.meshCytokines
dc.subject.meshUp-Regulation
dc.subject.meshPhosphorylation
dc.subject.meshFemale
dc.subject.meshMale
dc.titlePeripheral Brain Derived Neurotrophic Factor Precursor Regulates Pain as an Inflammatory Mediator
dc.typeJournal article
pubs.publication-statusPublished

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