Luo, C.Zhong, X.-L.Zhou, F.H.Li, J.-Y.Zhou, P.Xu, J.-M.Song, B.Li, C.-Q.Zhou, X.-F.Dai, R.-P.2021-12-032021-12-032016Scientific Reports, 2016; 6(1):27171-1-27171-112045-23222045-2322https://hdl.handle.net/2440/133548The 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.en© 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/Neurotrophic factorsSensory processingCells, CulturedAnimalsHumansMiceRatsPainDisease Models, AnimalExtracellular Signal-Regulated MAP KinasesBrain-Derived Neurotrophic FactorReceptors, Nerve Growth FactorNerve Tissue ProteinsInflammation MediatorsCytokinesUp-RegulationPhosphorylationFemaleMaleJournal article10.1038/srep271712021-12-03342172Zhou, F.H. [0000-0003-3113-1671]