Lappaconitine (LA) is a C-18 diterpene alkaloid isolated from Aconitum sinomontanum Nakai that has been shown to relieve mild to moderate discomfort. Various researchers have tried to explain the underlying mechanism of LA’s effects on chronic pain. This article uses metabolomics technology to investigate the metabolite alterations in the dorsal root ganglion (DRG) when lappaconitine hydrobromide (LAH) was injected in an inflammatory pain model, to explain the molecular mechanism of its analgesia from a metabolomics perspective. The pain model used in this study was a complete Freund’s adjuvant (CFA)-induced inflammatory pain model in rats. There were two treatment groups receiving different dosages of LAH (4 mg/kg LAH and 8 mg/kg LAH). The analgesic mechanism of LAH was investigated with an analgesic behavioral test, tissue sections, and metabolomics. The results of the analgesic behavioral experiment showed that both 4 mg/kg LAH and 8 mg/kg LAH could significantly improve the paw withdrawal latency (PWL) of rats. The tissue section results showed that LAH could reduce the inflammatory response and enlargement of the paw and ankle of rats and that there was no significant difference in the tissue sections of the DRG. The metabolomics results showed that retinol metabolism and glycerophospholipid metabolism in the CFA-induced inflammatory pain model were significantly affected and may exacerbate the inflammatory reactions and initiate persistent pain; in addition, the linoleic acid metabolism, arachidonic acid metabolism, and alanine, aspartate, and glutamate metabolism were also slightly affected. Among them, the alpha-linolenic acid metabolism was up-regulated after LAH treatment, while the retinol metabolism was down-regulated. These results suggest that LAH could effectively reduce inflammatory pain and might achieve this by regulating the lipid metabolism in the rat DRG.

中文翻译：

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拉帕乌汀氢溴酸盐 (LAH) 对炎症性疼痛的镇痛作用的代谢组学研究

Lappaconitine (LA) 是一种从乌头中分离出来的 C-18 二萜生物碱Nakai 已被证明可以缓解轻度至中度的不适。各种研究人员试图解释 LA 对慢性疼痛影响的潜在机制。本文利用代谢组学技术研究了在炎性疼痛模型中注射氢溴酸盐（LAH）后背根神经节（DRG）的代谢物变化，从代谢组学角度解释其镇痛的分子机制。本研究中使用的疼痛模型是完全弗氏佐剂 (CFA) 诱导的大鼠炎症性疼痛模型。有两个治疗组接受不同剂量的 LAH（4 mg/kg LAH 和 8 mg/kg LAH）。通过镇痛行为测试、组织切片和代谢组学研究了 LAH 的镇痛机制。镇痛行为实验结果表明，4 mg/kg LAH和8 mg/kg LAH均能显着改善大鼠的缩爪潜伏期（PWL）。组织切片结果显示，LAH可减轻大鼠足踝的炎症反应和增大，DRG组织切片无明显差异。代谢组学结果显示，CFA诱导的炎性疼痛模型中视黄醇代谢和甘油磷脂代谢受到显着影响，并可能加剧炎症反应并引发持续性疼痛；此外，亚油酸代谢、花生四烯酸代谢和丙氨酸、天冬氨酸、谷氨酸代谢也受到轻微影响。其中，LAH处理后α-亚麻酸代谢上调，而视黄醇代谢被下调。这些结果表明，LAH 可以有效减轻炎症性疼痛，并可能通过调节大鼠 DRG 中的脂质代谢来实现。