Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, China; Guangxi Engineering Research Center for Tissue & Organ Injury and Repair Medicine, Nanning, China; Guangxi Health Commission Key Laboratory of Basic Science and Prevention of Perioperative Organ Disfunction, Nanning, China.
Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, China; Guangxi Engineering Research Center for Tissue & Organ Injury and Repair Medicine, Nanning, China; Guangxi Health Commission Key Laboratory of Basic Science and Prevention of Perioperative Organ Disfunction, Nanning, China.
J Pain. 2024 Oct;25(10):104588. doi: 10.1016/j.jpain.2024.104588. Epub 2024 Jun 4.
Chronic pain often coincides with changes in gut microbiota composition. Yet, the role of gut microbiota in bone cancer pain (BCP) is still not fully understood. This study investigated the role of gut microbiota in BCP and the effect of oxymatrine (OMT) on gut microbiota in BCP. A BCP mice model was developed to assess gut microbiota composition, serum and brain tissue butyric acid levels, and blood-brain barrier (BBB) permeability. Microbiota transplantation was used to restore gut microbiota, and the effect of Clostridium butyricum or sodium butyrate (NaB) supplementation on pain-related behaviors and BBB integrity was evaluated. The potential benefits of OMT on gut microbiota composition, peroxisome proliferator-activated receptor gamma (PPARγ)/cyclooxygenase-2 (COX-2) signaling, BBB integrity, and pain-related behaviors were also explored. BCP significantly altered gut microbiota composition and reduced serum and brain tissue butyric acid levels. Additionally, BBB permeability increased considerably in the BCP group compared with sham and control mice. Microbiota transplantation, as well as C butyricum or NaB supplementation, ameliorated pain-related behaviors and BBB integrity; the supplementation of C butyricum or NaB boosted brain-tight-junction protein expression, potentially through modulating PPARγ/COX-2 signaling. OMT influenced gut microbiota composition and regulated PPARγ/COX-2 signaling in the BCP model, improving pain-related behaviors and BBB integrity. BCP affects gut microbiota composition and butyric acid levels. Modulating gut microbiota and butyric acid levels through transplantation or supplementation may alleviate BCP. OMT shows potential as a treatment by altering gut microbiota composition and regulating PPARγ/COX-2 signaling. These findings provide new insights into BCP pathophysiology and possible treatments. PERSPECTIVE: This study explores the impact of gut microbiota on BCP. Microbiota transplantation alleviates BCP and enhances BBB integrity. Also, C butyricum or NaB improves BBB via PPARγ/COX-2. OMT, a BCP treatment, modifies microbiota by regulating PPARγ/COX-2, in turn improving pain and BBB integrity. These findings suggest a therapeutic approach, emphasizing clinical relevance in targeting gut microbiota and restoring butyric acid levels.
慢性疼痛通常与肠道微生物群落组成的变化同时发生。然而，肠道微生物群在骨癌痛（BCP）中的作用仍不完全清楚。本研究旨在探讨肠道微生物群在 BCP 中的作用，以及氧化苦参碱（OMT）对 BCP 中肠道微生物群的影响。建立了 BCP 小鼠模型，以评估肠道微生物群落组成、血清和脑组织丁酸水平以及血脑屏障（BBB）通透性。使用菌群移植来恢复肠道微生物群，并评估丁酸梭菌或丁酸钠（NaB）补充对疼痛相关行为和 BBB 完整性的影响。还探讨了 OMT 对肠道微生物群落组成、过氧化物酶体增殖物激活受体γ（PPARγ）/环氧化酶-2（COX-2）信号、BBB 完整性和疼痛相关行为的潜在益处。BCP 显著改变了肠道微生物群落组成，降低了血清和脑组织丁酸水平。此外，与假手术和对照组小鼠相比，BCP 组的 BBB 通透性显著增加。菌群移植以及 C 梭菌或 NaB 补充均改善了疼痛相关行为和 BBB 完整性；C 梭菌或 NaB 的补充增强了脑紧密连接蛋白的表达，可能通过调节 PPARγ/COX-2 信号。OMT 影响 BCP 模型中的肠道微生物群落组成并调节 PPARγ/COX-2 信号，从而改善疼痛相关行为和 BBB 完整性。BCP 影响肠道微生物群落组成和丁酸水平。通过移植或补充调节肠道微生物群和丁酸水平可能缓解 BCP。OMT 通过改变肠道微生物群落组成和调节 PPARγ/COX-2 信号显示出作为一种治疗方法的潜力。这些发现为 BCP 病理生理学和可能的治疗方法提供了新的见解。观点：本研究探讨了肠道微生物群对 BCP 的影响。菌群移植缓解了 BCP 并增强了 BBB 完整性。此外，C 梭菌或 NaB 通过 PPARγ/COX-2 改善了 BBB。OMT 是 BCP 的一种治疗方法，通过调节 PPARγ/COX-2 来改变微生物群，从而改善疼痛和 BBB 完整性。这些发现表明了一种治疗方法，强调了靶向肠道微生物群和恢复丁酸水平的临床相关性。
