SZAP 通过抑制痛觉过敏和 TRPV1、P2X3 发挥对 CIA 大鼠风湿痛的镇痛作用。

SZAP exerts analgesic effects on rheumatalgia in CIA rats by suppressing pain hyperalgesia and inhibiting TRPV1 and P2X3.

机构信息

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, PR China; Institute of Meterial Medica Integration and Transformation for Brain Disorders, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, PR China.

Department of Pathology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.

出版信息

J Ethnopharmacol. 2022 Feb 10;284:114780. doi: 10.1016/j.jep.2021.114780. Epub 2021 Oct 30.

DOI:10.1016/j.jep.2021.114780

PMID:34728318

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

ShexiangZhuifeng Analgesic Plaster (SZAP) is a traditional Chinese medicine and transdermal formulation composed of many Chinese herbs and active compounds. SZAP was recently approved by the China Food and Drug Administration for the treatment of pain associated with osteoarticular diseases and is preferred by most rheumatoid arthritis patients in China. However, its mechanism has not been elucidated in detail.

AIM OF THE STUDY

We sought to determine the analgesic effect of SZAP in collagen-induced arthritis (CIA) rats and explore the underlying mechanisms of pain transmission, such as via the TRPV1 and P2X3 receptors.

METHODS

After CIA was established, rats were treated with SZAP for 7 days. Paw thickness, arthritis score, and haematoxylin and eosin staining were used to evaluate the effectiveness of SZAP. Paw withdrawal threshold (PWT) and tail-flick latency (TFL) were used to estimate the analgesic effect of SZAP. The levels of PGE, BK, 5-HT, SP, and CGRP in the serum and synovium were determined using ELISA kits, and ATP in the synovium was measured using HPLC. The expression of TRPV1 and P2X3 in the DRG was detected using western blotting and immunofluorescence. TRPV1 and P2X3 agonists were further used to determine the analgesic effects of SZAP on CIA rats based on PWT and TFL.

RESULTS

SZAP not only significantly ameliorated arthritis scores and paw thickness by improving the pathological damage of synovial joints, but also remarkably alleviated pain in CIA rats. Further, treatment with SZAP significantly reduced peripheral 5-HT, PGE BK, SP, CGRP, and ATP. Additionally, the expression of TRPV1 and P2X3 in the DRG was markedly downregulated by SZAP. Interestingly, the analgesic effect of SZAP was weakened (reduction of PWT and TFL) when TRPV1 and P2X3 were activated by capsaicin or α,β-meATP, respectively.

CONCLUSION

SZAP ameliorates rheumatalgia by suppressing hyperalgesia and pain transmission through the inhibition of TRPV1 and P2X3 in the DRG of CIA rats.

摘要

民族药理学相关性

麝香追风止痛膏（SZAP）是一种中药透皮制剂，由多种中草药和活性化合物组成。SZAP 最近已被中国食品药品监督管理局批准用于治疗与骨关节炎相关的疼痛，是中国大多数类风湿关节炎患者的首选。然而，其作用机制尚未详细阐明。

研究目的

我们旨在确定 SZAP 在胶原诱导性关节炎（CIA）大鼠中的镇痛作用，并探讨疼痛传递的潜在机制，例如通过 TRPV1 和 P2X3 受体。

方法

在 CIA 建立后，大鼠用 SZAP 治疗 7 天。通过爪厚度、关节炎评分和苏木精-伊红染色评估 SZAP 的疗效。通过测定爪退缩阈值（PWT）和尾部闪烁潜伏期（TFL）来评估 SZAP 的镇痛作用。采用 ELISA 试剂盒测定血清和滑膜中 PGE、BK、5-HT、SP 和 CGRP 的水平，采用 HPLC 测定滑膜中 ATP 的含量。采用 Western 印迹和免疫荧光法检测 DRG 中 TRPV1 和 P2X3 的表达。进一步使用 TRPV1 和 P2X3 激动剂，根据 PWT 和 TFL，确定 SZAP 对 CIA 大鼠的镇痛作用。

结果

SZAP 不仅通过改善滑膜关节的病理损伤显著改善关节炎评分和爪厚度，而且显著缓解 CIA 大鼠的疼痛。此外，SZAP 治疗还显著降低外周 5-HT、PGE、BK、SP、CGRP 和 ATP。此外，DRG 中 TRPV1 和 P2X3 的表达明显下调。有趣的是，当分别用辣椒素或α，β- meATP 激活 TRPV1 和 P2X3 时，SZAP 的镇痛作用减弱（PWT 和 TFL 降低）。