title: Peripheral Brain Derived Neurotrophic Factor Precursor Regulates Pain as an Inflammatory Mediator.
abstract: The 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 intra-plantar 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 anti-proBDNF pretreatment may alleviate the development of inflammatory pain.
authors.affiliation: Department of Anesthesiology, The Second Xiang-Ya Hospital of Central South University, Changsha 410000, Hunan, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Luo
authors.affiliation: Department of Anatomy and Neurobiology, School of Basic Medical of Science, Central South University, Changsha 410000, Hunan, China.
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Zhong
authors.affiliation: School of Pharmacy and Medical Sciences, Division of Health Sciences, University of South Australia, Adelaide, SA 5000, Australia.
authors.forename: Fiona H
authors.initials: FH
authors.lastname: Zhou
authors.affiliation: School of Pharmacy and Medical Sciences, Division of Health Sciences, University of South Australia, Adelaide, SA 5000, Australia.
authors.forename: Jia-Yi
authors.initials: JY
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The Second Xiang-Ya Hospital of Central South University, Changsha 410000, Hunan, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, The Second Xiang-Ya Hospital of Central South University, Changsha 410000, Hunan, China.
authors.forename: Jun-Mei
authors.initials: JM
authors.lastname: Xu
authors.affiliation: Shanghai Yile Biotechnology Co., Ltd. 466 Yindu Road, Shanghai 200231, P.R.China.
authors.forename: Bo
authors.initials: B
authors.lastname: Song
authors.affiliation: Department of Anatomy and Neurobiology, School of Basic Medical of Science, Central South University, Changsha 410000, Hunan, China.
authors.forename: Chang-Qi
authors.initials: CQ
authors.lastname: Li
authors.affiliation: School of Pharmacy and Medical Sciences, Division of Health Sciences, University of South Australia, Adelaide, SA 5000, Australia.
authors.forename: Xin-Fu
authors.initials: XF
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, The Second Xiang-Ya Hospital of Central South University, Changsha 410000, Hunan, China.
authors.forename: Ru-Ping
authors.initials: RP
authors.lastname: Dai
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010146:Pain / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D018836:Inflammation Mediators; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor; C579455:BDNF protein, human; D048049:Extracellular Signal-Regulated MAP Kinases