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）是导致腰痛的主要因素。炎症和疼痛之间存在密切的关系。雌激素可以影响炎症，并可能在 IDD 和疼痛中发挥关键作用。物质 P (SP) 还可以调节椎间盘 (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。9周龄的C57BL/6雌性小鼠分为4组：假手术（sham）、卵巢切除（OVX）、卵巢切除加雌激素替代治疗（ERT）组（OVX+E2）、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。免疫组化研究和实时定量 PCR 用于 SP、NK1R、IL-1β、IL-6 和 TNF-α 在蛋白质和基因水平上的 IVD 检查和比较。OVX后NP细胞TNF-α、IL-1β、IL-6、SP、NK1R基因和蛋白表达较假手术组显着增加。ERT 可以扭转这些影响。ERT 在 OVX 小鼠的 IDD 中发挥抗炎和抗痛觉过敏的作用。NK1R 激动剂可显着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 促炎因子的介质。雌激素可能通过两种方式影响IVD炎症：一是直接影响促炎细胞因子水平，二是通过调节SP。ERT 在 OVX 小鼠的 IDD 中发挥抗炎和抗痛觉过敏的作用。NK1R 激动剂可显着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 促炎因子的介质。雌激素可能通过两种方式影响IVD炎症：一是直接影响促炎细胞因子水平，二是通过调节SP。ERT 在 OVX 小鼠的 IDD 中发挥抗炎和抗痛觉过敏的作用。NK1R 激动剂可显着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 促炎因子的介质。雌激素可能通过两种方式影响IVD炎症：一是直接影响促炎细胞因子水平，二是通过调节SP。