Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, 185 S. Orange Ave., MSB, E-661, Newark, NJ, 07103, USA.
Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, (Original named "Shanghai First People's Hospital"), No 100, Haining Road, Hongkou District, Shanghai, 200080, China.
Mol Neurobiol. 2019 Oct;56(10):7085-7096. doi: 10.1007/s12035-019-1545-y. Epub 2019 Apr 11.
Fibroblast growth factor-inducible-14 (Fn14), a receptor for tumor necrosis-like weak inducer of apoptosis, is expressed in the neurons of dorsal root ganglion (DRG). Its mRNA is increased in the injured DRG following peripheral nerve injury. Whether this increase contributes to neuropathic pain is unknown. We reported here that peripheral nerve injury caused by spinal nerve ligation (SNL) increased the expression of Fn14 at both protein and mRNA levels in the injured DRG. Blocking this increase attenuated the development of SNL-induced mechanical, thermal, and cold pain hypersensitivities. Conversely, mimicking this increase produced the increases in the levels of phosphorylated extracellular signal-regulated kinase ½ and glial fibrillary acidic protein in ipsilateral dorsal horn and the enhanced responses to mechanical, thermal, and cold stimuli in the absence of SNL. Mechanistically, the increased Fn14 activated the NF-κB pathway through promoting the translocation of p65 into the nucleus of the injured DRG neurons. Our findings suggest that Fn14 may be a potential target for the therapeutic treatment of peripheral neuropathic pain.
成纤维细胞生长因子诱导因子 14（Fn14）是肿瘤坏死样凋亡弱诱导物的受体，在背根神经节（DRG）的神经元中表达。其 mRNA 在周围神经损伤后损伤的 DRG 中增加。这种增加是否有助于神经性疼痛尚不清楚。我们在这里报道，脊柱神经结扎（SNL）引起的周围神经损伤导致损伤的 DRG 中 Fn14 的蛋白和 mRNA 水平均增加。阻断这种增加可减轻 SNL 诱导的机械、热和冷痛敏的发展。相反，模拟这种增加会导致同侧背角中磷酸化细胞外信号调节激酶 1/2 和神经胶质纤维酸性蛋白的水平增加，并在没有 SNL 的情况下增强对机械、热和冷刺激的反应。从机制上讲，增加的 Fn14 通过促进 p65 向损伤的 DRG 神经元核内易位来激活 NF-κB 途径。我们的研究结果表明，Fn14 可能是治疗周围神经性疼痛的潜在靶点。
