Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Lu, Shanghai, 200025, China.
Department of Spinal Surgery, Peking University People's Hospital, Peking University, Beijing, 100044, China.
Inflammation. 2021 Apr;44(2):506-517. doi: 10.1007/s10753-020-01347-1. Epub 2020 Sep 23.
Intervertebral disc degeneration (IDD) is a main contributor to low back pain. A close relationship exists between inflammation and pain. Estrogen can affect inflammation and may play a crucial role in IDD and pain. Substance P (SP) can also regulate the expression of pro-inflammatory cytokines in intervertebral disc (IVD). This study aimed to investigate the potential role of SP in estrogen regulation of IDD. Nine-week-old C57BL/6 female mice were divided into four groups as follows: sham surgery (sham), ovariectomy (OVX), ovariectomy plus estrogen replacement therapy (ERT) group (OVX+E2), and ovariectomy, ERT plus neurokinin 1 receptor (NK1R) agonist (OVX+E2+G). Serum E2, body, and uterus weight were recorded. Immunohistochemistry study and quantitative real-time PCR were used for SP, NK1R, IL-1β, IL-6, and TNF-α examination and comparison in IVD at protein and gene levels. After OVX, the gene and protein expression of TNF-α, IL-1β, IL-6, SP, and NK1R in NP cells significantly increased compared with the sham group. ERT can reverse these impacts. ERT plays anti-inflammatory and anti-hyperalgesic roles in IDD of OVX mice. The estrogen-induced changes of the pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6, are significantly inhibited by NK1R agonists. SP may be a mediator of estrogen regulating pro-inflammatory factors in IDD. Estrogen may affect IVD inflammation through two ways: one is to directly affect the level of pro-inflammatory cytokines and the other is by means of modulation of SP.
椎间盘退变（IDD）是导致下腰痛的主要原因。炎症与疼痛之间存在密切关系。雌激素可以影响炎症，并且在 IDD 和疼痛中可能发挥关键作用。P 物质（SP）也可以调节椎间盘（IVD）中促炎细胞因子的表达。本研究旨在探讨 SP 在雌激素调节 IDD 中的潜在作用。将 9 周龄 C57BL/6 雌性小鼠分为 4 组：假手术（sham）、卵巢切除术（OVX）、卵巢切除加雌激素替代疗法（ERT）组（OVX+E2）和卵巢切除、ERT 加神经激肽 1 受体（NK1R）激动剂（OVX+E2+G）。记录血清 E2、体重和子宫重量。采用免疫组织化学研究和实时定量 PCR 检测和比较 IVD 中 SP、NK1R、IL-1β、IL-6 和 TNF-α的蛋白和基因水平。OVX 后，NP 细胞中 TNF-α、IL-1β、IL-6、SP 和 NK1R 的基因和蛋白表达与 sham 组相比显著增加。ERT 可以逆转这些影响。ERT 在 OVX 小鼠 IDD 中发挥抗炎和抗痛觉过敏作用。NK1R 激动剂显著抑制雌激素诱导的促炎细胞因子 TNF-α、IL-1β 和 IL-6 的变化。SP 可能是雌激素调节 IDD 中促炎因子的介质。雌激素可能通过两种方式影响 IVD 炎症：一种是直接影响促炎细胞因子的水平，另一种是通过调节 SP。
