Zhao Wenjing, Ma Lulin, Deng Daling, Han Linlin, Xu Feng, Zhang Tianhao, Wang Yafeng, Huang Shiqian, Ding Yuanyuan, Shu Shaofang, Chen Xiangdong
Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277, Jiefang Avenue, Wuhan, 430022, China.
Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Mol Neurobiol. 2025 Jan;62(1):169-183. doi: 10.1007/s12035-024-04249-7. Epub 2024 Jun 3.
Approximately one-third of postoperative patients are troubled by postoperative pain. Effective treatments are still lacking. The aim of this study is to investigate the role of brain-derived neurotrophic factor (BDNF)-VGF (non-acronymic) in dorsal root ganglia (DRG) in postoperative pain. Pain behaviors were assessed through measurements of paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). Transcriptome analysis was conducted to identify potential targets associated with postoperative pain. Western blotting, immunofluorescence, and ELISA were employed to further detect macrophage activation as well as the expression of BDNF, VGF, TNF-α, IL-1β, and IL-6. Results showed that plantar incision induced both mechanical and thermal hyperalgesia. Transcriptome analysis suggested that plantar incision caused upregulation of BDNF and VGF. The expressions of BDNF and VGF were upregulated in isolectin B4-positive (IB4) and calcitonin gene-related peptide-positive (CGRP) neurons, rather than neurofilament 200-positive (NF200) neurons. The activation of BDNF-VGF pathway upregulated expression of IL-6, TNF-α, and IL-1β and promoted the activation of macrophages. In conclusion, BDNF-VGF pathway aggravates acute postoperative pain by promoting macrophage activation and pro-inflammatory cytokine production, which may provide a new target for the treatment of postoperative pain.
大约三分之一的术后患者会受到术后疼痛的困扰。目前仍缺乏有效的治疗方法。本研究的目的是探讨背根神经节（DRG）中脑源性神经营养因子（BDNF）-VGF（非首字母缩略词）在术后疼痛中的作用。通过测量爪部退缩阈值（PWT）和爪部退缩潜伏期（PWL）来评估疼痛行为。进行转录组分析以确定与术后疼痛相关的潜在靶点。采用蛋白质免疫印迹法、免疫荧光法和酶联免疫吸附测定法进一步检测巨噬细胞的激活以及BDNF、VGF、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）的表达。结果显示，足底切口可诱导机械性和热性痛觉过敏。转录组分析表明，足底切口导致BDNF和VGF上调。BDNF和VGF的表达在异凝集素B4阳性（IB4）和降钙素基因相关肽阳性（CGRP）神经元中上调，而在神经丝200阳性（NF200）神经元中未上调。BDNF-VGF通路的激活上调了IL-6、TNF-α和IL-1β的表达，并促进了巨噬细胞的激活。总之，BDNF-VGF通路通过促进巨噬细胞激活和促炎细胞因子产生而加重急性术后疼痛，这可能为术后疼痛的治疗提供新的靶点。
