PURPOSE We aimed to investigate the pharmacological effects and mechanisms of the Aitongping formula for treating cancer pain. METHODS We enrolled 60 cancer patients with Numeric Rating Scale above 4 and grouped them randomly as a Control group (N = 30) and a Patch group (N = 30). We also established bone cancer mice models via tumor implantation. And the animal groups were established as a Sham group, a tumor cell implantation (TCI) group, a TCI + Patch group, and a Patch group. RESULTS After the validation of successful tumor implantation, we identified candidate miRNAs and genes that were dysregulated in TCI mice and compared their expressions between different mice groups. We also observed the effect of Aitongping patch in vitro in mice primary microglia. The time to disease progression and cancer stability were prolonged by Aitongping patch in cancer patients. And the daily morphine dose was lower, and patients' quality of life was improved in the Patch group. Moreover, Aitongping patch alleviated cancer pain and inhibited microglia activation after the successful implantation of bone tumor in TCI mice. We also observed the dysregulation of miR-150-5p and chemokine CXC motif ligand 12 (CXCL12) mRNA in TCI mice. And CXCL12 was found to be targeted by miR-150-5p. Aitongping patch was found to upregulate miR-150-5p and downregulate CXCL12 in vivo and in vitro. CONCLUSION Aitongping patch could alleviate cancer pain via suppressing microglia activation, and the downregulation of miR-150-5p, as well as the upregulation of CXCL12 mRNA and protein, induced by tumor implantation or lipopolysaccharide stimulation, was restored by Aitongping treatment.

中文翻译：

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癌痛平贴片可以通过抑制小胶质细胞激活和调节 miR-150-5p/CXCL12 信号传导来减轻癌症疼痛。

目的我们的目的是探讨癌痛平方治疗癌性疼痛的药理作用和机制。方法 我们招募了 60 名数字评定量表高于 4 的癌症患者，并将他们随机分为对照组 (N = 30) 和补丁组 (N = 30)。我们还通过肿瘤植入建立了骨癌小鼠模型。动物组分为Sham组、肿瘤细胞植入(TCI)组、TCI+Patch组、Patch组。结果在验证肿瘤成功植入后，我们鉴定了TCI小鼠中失调的候选miRNA和基因，并比较了它们在不同小鼠组之间的表达。我们还在体外观察了癌痛平贴剂对小鼠原代小胶质细胞的作用。癌痛平贴剂可延长癌症患者的疾病进展时间和癌症稳定性。贴片组的每日吗啡剂量较低，患者的生活质量得到改善。此外，癌痛平贴剂在TCI小鼠骨肿瘤成功植入后可减轻癌痛并抑制小胶质细胞活化。我们还在 TCI 小鼠中观察到 miR-150-5p 和趋化因子 CXC 基序配体 12 (CXCL12) mRNA 的失调。并且发现CXCL12是miR-150-5p的靶标。研究发现，艾痛平贴剂在体内和体外均可上调 miR-150-5p 并下调 CXCL12。结论癌痛平贴剂可通过抑制小胶质细胞活化来减轻癌痛，癌痛平治疗可恢复肿瘤植入或脂多糖刺激引起的miR-150-5p下调以及CXCL12 mRNA和蛋白上调。