Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan.
Spine (Phila Pa 1976). 2018 Jan 1;43(1):E7-E15. doi: 10.1097/BRS.0000000000002223.
An experimental animal study.
To investigate the relationship between pain-related behavior and the expression of neurotrophic factors in the dorsal root ganglion (DRG) and spinal cord (SC) using a nucleus pulposus (NP) rat model.
Neurotrophic factors are released from activated glial cells and are associated with pain-related behavior. Nerve growth factor (NGF) is a neurotrophic factor that is induced by inflammation.
Rats were divided into an NP group (n = 94) and a sham-operated group (n = 46). NP harvested from the tail was applied to the left L5 DRG. Rats in the NP group were then divided into five subgroups: one non-treatment and four treatment groups. In the treatment groups, a dose of anti-NGF antibody or phosphate-buffered saline was administered into the DRG. Behavioral testing was performed to investigate the mechanical withdrawal threshold of the left hind paw for all groups. Immunohistochemical localization of NGF, phosphorylated p38 (p38), and brain-derived neurotrophic factor (BDNF) in the DRGs and SCs was performed, and the numbers of immunoreactive (IR) cells were counted.
The withdrawal threshold in the nontreatment NP group was significantly decreased for 35 days, and that of the middle- and high-dose treatment rats was significantly higher than the phosphate-buffered saline group values. In the DRG, NGF-IR, p38-IR, and BDNF-IR cells were increased for days 21. In the SC, BDNF-IR, and p38-IR cells were increased from days 7 to 21.
In the DRG, NGF expression increased, mechanical thresholds were reduced, and p38 and BDNF expression was increased in the NP group. p38 and BDNF expression was increased in SC neurons during the same period. Inhibition of NGF may be a potential treatment for neuropathic pain due to lumbar disc herniation.
一项实验动物研究。
使用椎间盘(NP)大鼠模型,研究背根神经节(DRG)和脊髓(SC)中与疼痛相关行为的神经生长因子(NGF)表达与疼痛相关行为之间的关系。
神经营养因子由激活的神经胶质细胞释放,与疼痛相关行为有关。神经生长因子(NGF)是一种由炎症诱导的神经营养因子。
将大鼠分为 NP 组(n=94)和假手术组(n=46)。从尾部取出 NP 并应用于左侧 L5 DRG。然后将 NP 组大鼠分为五组:一组未治疗组和四组治疗组。在治疗组中,将抗 NGF 抗体或磷酸盐缓冲液(PBS)注入 DRG。对所有组进行左后爪机械退缩阈值的行为测试。对 DRG 和 SC 中 NGF、磷酸化 p38(p38)和脑源性神经营养因子(BDNF)的免疫组织化学定位进行了检测,并对免疫反应性(IR)细胞的数量进行了计数。
未治疗的 NP 组大鼠的退缩阈值在第 35 天明显下降,中剂量和高剂量治疗组大鼠的退缩阈值明显高于 PBS 组。在 DRG 中,NGF-IR、p38-IR 和 BDNF-IR 细胞在第 21 天增加。在 SC 中,BDNF-IR 和 p38-IR 细胞从第 7 天到第 21 天增加。
在 NP 组的 DRG 中,NGF 表达增加,机械阈值降低,p38 和 BDNF 表达增加。在同一时期,SC 神经元中 p38 和 BDNF 的表达增加。抑制 NGF 可能是治疗腰椎间盘突出症引起的神经病理性疼痛的一种潜在方法。