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

Cong Luo, Xiao Lin Zhong, Fiona Zhou, Jia Yi Li, Pei Zhou, Jun Mei Xu, Bo Song, Chang Qi Li, Xin Fu Zhou, Ru Ping Dai

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18 Citations (Scopus)

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.

Original languageEnglish
Article number27171
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 2 Jun 2016

ASJC Scopus subject areas

  • General

Cite this

Luo, C., Zhong, X. L., Zhou, F., Li, J. Y., Zhou, P., Xu, J. M., ... Dai, R. P. (2016). Peripheral Brain Derived Neurotrophic Factor Precursor Regulates Pain as an Inflammatory Mediator. Scientific Reports, 6, [27171]. https://doi.org/10.1038/srep27171