Department of Clinical Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, China.
School of Pharmacy, Xuzhou Medical University, Xuzhou, 221000, China.
Inflamm Res. 2022 Apr;71(4):485-495. doi: 10.1007/s00011-022-01561-7. Epub 2022 Mar 17.
The transient receptor potential vanilloid subtype 1 (TRPV1) channel is considered to play an important regulatory role in the process of pain. The purpose of this study is to observe the change characteristics of TRPV1 channel in MSU-induced gouty arthritis and to find a new target for clinical treatment of gout pain.
Acute gouty arthritis was induced by injection of monosodium urate (MSU) crystals into the ankle joint of mice. The swelling degree was evaluated by measuring the circumference of the ankle joint. Mechanical hyperalgesia was conducted using the electronic von Frey. Calcium fluorescence and TRPV1 current were recorded by applying laser scanning confocal microscope and patch clamp in dorsal root ganglion (DRG) neurons, respectively.
MSU treatment resulted in significant inflammatory response and mechanical hyperalgesia. The peak swelling degree appeared at 12 h, and the minimum pain threshold appeared at 8 h after MSU treatment. The fluorescence intensity of capsaicin-induced calcium response and TRPV1 current were increased in DRG cells from MSU-treated mice. The number of cells that increased calcium response after MSU treatment was mainly distributed in small-diameter DRG cells. However, the action potential was not significantly changed in small-diameter DRG cells after MSU treatment.
These findings identified an important role of TRPV1 in mediating mechanical hyperalgesia in MSU-induced gouty arthritis and further suggest that TRPV1 can be regarded as a potential new target for the clinical treatment of gouty arthritis.
瞬时受体电位香草酸亚型 1（TRPV1）通道被认为在疼痛过程中发挥重要的调节作用。本研究旨在观察 MSU 诱导的痛风性关节炎中 TRPV1 通道的变化特征，并寻找痛风疼痛临床治疗的新靶点。
通过向小鼠踝关节注射单钠尿酸盐（MSU）晶体来诱导急性痛风性关节炎。通过测量踝关节周长来评估肿胀程度。使用电子 von Frey 进行机械性痛觉过敏检测。应用激光扫描共聚焦显微镜和膜片钳技术分别在背根神经节（DRG）神经元中记录钙荧光和 TRPV1 电流。
MSU 处理导致明显的炎症反应和机械性痛觉过敏。肿胀程度的峰值出现在 12 小时，MSU 处理后 8 小时出现最小疼痛阈值。MSU 处理的 DRG 细胞中辣椒素诱导的钙反应和 TRPV1 电流的荧光强度增加。MSU 处理后增加钙反应的细胞数量主要分布在小直径 DRG 细胞中。然而，MSU 处理后小直径 DRG 细胞的动作电位没有明显变化。
这些发现表明 TRPV1 在介导 MSU 诱导的痛风性关节炎中的机械性痛觉过敏中起重要作用，并进一步表明 TRPV1 可以作为痛风性关节炎临床治疗的潜在新靶点。
