Peripheral Brain Derived Neurotrophic Factor Precursor Regulates Pain as an Inflammatory Mediator.
Peripheral Brain Derived Neurotrophic Factor Precursor Regulates Pain as an Inflammatory Mediator.
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外周脑源性神经营养因子前体作为炎症介质调节疼痛
DOI：
10.1038/srep27171
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发表时间：
2016-06-02
影响因子：
4.6
通讯作者：
Dai RP
中科院分区：
文献类型：
--
作者：
Luo C;Zhong XL;Zhou FH;Li JY;Zhou P;Xu JM;Song B;Li CQ;Zhou XF;Dai RP
脑源性神经营养因子 (proBDNF) 的前体是未加工的 BDNF 基因产物，与其受体结合并发挥与成熟 BDNF 相反的生物学功能。 proBDNF 在外周组织中表达，但外周 proBDNF 的功能仍不清楚。在这里，我们发现在炎症性疼痛时，局部组织的神经纤维和炎症细胞中的 proBDNF 及其主要受体 p75 泛神经营养因子受体上调。多克隆抗体中和 proBDNF 可减轻不同炎性疼痛模型中的疼痛。通过注射外源性 proBDNF 或异位过度表达进行单侧足底内补充 proBDNF 会导致疼痛过敏并诱导脊髓磷酸化细胞外信号调节激酶激活。注射外源性proBDNF可诱导炎症细胞浸润和促炎细胞因子的激活，表明炎症反应有助于proBDNF的促痛作用。最后，我们产生了单克隆抗 proBDNF 抗体，可以从生物学角度阻断 proBDNF。单克隆 Ab-proBDNF 的施用可减轻各种类型的炎性疼痛和手术疼痛。因此，外周 proBDNF 是一种潜在的疼痛介质，抗 proBDNF 预处理可以减轻炎性疼痛的发展。
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.