Department of Urology, Guiqian International General Hospital, Guiyang, P. R. China.
Department of Pathology, Guiqian International General Hospital, Guiyang, P. R. China.
In Vivo. 2024 Mar-Apr;38(2):691-698. doi: 10.21873/invivo.13490.
BACKGROUND/AIM: This study aimed to investigate the role of NOTCH receptor 1 (NOTCH1)-mediated activation of microglia in the L5-S2 spinal dorsal horn in chronic prostatitis pain.
Rats were divided into chronic prostatitis (CP) group and control group. Complete Freund's adjuvant was injected into the prostate, and prostate pathology and pain-related behavior were monitored to assess the successful establishment of the CP-related pain model. The dorsal horn of the L5-S2 spinal cord was collected for the detection of ionized calcium-binding adapter molecule 1 (IBA-1) and NOTCH1 expression by quantitative real time polymerase chain reaction and the detection of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) by enzyme-linked immunosorbent assay. Electrical excitability was assessed with whole-cell patch clamp. In addition, NOTCH1 receptor inhibitor or inhibitor of microglial cell activation was injected into the subarachnoid space, and the pro-inflammatory cytokines in the spinal cord were detected.
In the CP group, the expression of NOTCH1, IBA-1, TNF-α and IL-1β began to increase at 4 days, peaked at 12 days, and began to decline at 24 days, and it was significantly higher than in the control group (p<0.01). Inhibition of microglia or NOTCH1 receptor markedly reduced the content of TNF-α and IL-1β in the spinal cord (p<0.05). At 4, 12 and 24 days, the amplitude and frequency of neuronal action potential increased and the threshold decreased markedly as compared to the control group (p<0.05), and spontaneous action potential was noted.
NOTCH1 mediates the activation of microglia in the L5-S2 spinal cord, leading to the secretion of inflammatory factors and enhanced electrical excitability of neurons, which is related to persistent and refractory chronic prostatitis-related pain.
背景/目的：本研究旨在探讨 NOTCH 受体 1（NOTCH1）介导的小胶质细胞激活在慢性前列腺炎疼痛中的 L5-S2 脊髓背角中的作用。
大鼠分为慢性前列腺炎（CP）组和对照组。向前列腺内注射完全弗氏佐剂，并监测前列腺病理学和疼痛相关行为，以评估 CP 相关疼痛模型的成功建立。采集 L5-S2 脊髓背角，通过定量实时聚合酶链反应检测离子钙结合接头分子 1（IBA-1）和 NOTCH1 的表达，并通过酶联免疫吸附试验检测肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）。用全细胞膜片钳评估电兴奋性。此外，向蛛网膜下腔注射 NOTCH1 受体抑制剂或小胶质细胞激活抑制剂，并检测脊髓中的促炎细胞因子。
CP 组中，NOTCH1、IBA-1、TNF-α 和 IL-1β 的表达于 4 天开始增加，12 天达到高峰，24 天开始下降，明显高于对照组（p<0.01）。抑制小胶质细胞或 NOTCH1 受体明显降低了脊髓中 TNF-α 和 IL-1β 的含量（p<0.05）。与对照组相比，4、12 和 24 天时神经元动作电位的幅度和频率明显增加，阈值明显降低（p<0.05），并出现自发性动作电位。
NOTCH1 介导 L5-S2 脊髓中小胶质细胞的激活，导致炎症因子的分泌和神经元电兴奋性增强，与持续性和难治性慢性前列腺炎相关疼痛有关。
