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阿片类药物治疗癌痛的研究进展
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Abstract:
本文聚焦阿片类药物与癌痛死亡率的关系，阐述其在癌痛治疗中的关键地位，剖析吗啡、羟考酮、芬太尼等常见阿片类药物促进肿瘤进展的多方面机制，涵盖对肿瘤细胞增殖、免疫功能、血管生成的影响等。同时介绍阿片类药物常见副作用及治疗方法，强调便秘治疗的多种手段。综合分析得出阿片类药物在癌痛管理中利弊共存，临床使用需权衡考量，制定个性化方案，加强副作用管理。未来应深入探究潜在机制，为临床决策提供更精准依据，在有效控制癌痛的同时降低肿瘤进展与死亡风险。
This article focuses on the relationship between opioids and cancer pain mortality, elucidating their critical role in cancer pain management, and analyzing the multifaceted mechanisms by which common opioids such as morphine, oxycodone, and fentanyl promote tumor progression, including effects on tumor cell proliferation, immune function, and angiogenesis. It also introduces common side effects of opioids and their treatments, emphasizing various approaches for managing constipation. A comprehensive analysis reveals that opioids present a double-edged sword in cancer pain management, requiring clinicians to balance benefits and risks, develop personalized regimens, and enhance side effect management. Future research should delve into underlying mechanisms to provide precise scientific evidence for clinical decision-making, aiming to control cancer pain effectively while reducing tumor progression and mortality risks.
| [1] | Pacifici, G.M. (2016) Metabolism and Pharmacokinetics of Morphine in Neonates: A Review. Clinics, 71, 474-480. https://doi.org/10.6061/clinics/2016(08)11 |
| [2] | Lu, H., Zhang, H., Weng, M., Zhang, J., Jiang, N., Cata, J.P., et al. (2021) Morphine Promotes Tumorigenesis and Cetuximab Resistance via EGFR Signaling Activation in Human Colorectal Cancer. Journal of Cellular Physiology, 236, 4445-4454. https://doi.org/10.1002/jcp.30161 |
| [3] | Taghavi, S.F., Shahsavari, Z., Adjaminezhad-Fard, F., Ghorbani, M., Ghorbanhosseini, S.S., Salimi, V., et al. (2023) Evaluating the Expression Pattern of the Opioid Receptor in Pituitary Neuroendocrine Tumors (PitNET) and the Role of Morphine and Naloxone in the Regulation of Pituitary Cell Line Growth and Apoptosis. Biomedicine & Pharmacotherapy, 157, Article 114022. https://doi.org/10.1016/j.biopha.2022.114022 |
| [4] | Wang, K., Wang, J., Liu, T., Yu, W., Dong, N., Zhang, C., et al. (2021) Morphine-3-Glucuronide Upregulates PD-L1 Expression via TLR4 and Promotes the Immune Escape of Non-Small Cell Lung Cancer. Cancer Biology and Medicine, 18, 155-171. https://doi.org/10.20892/j.issn.2095-3941.2020.0442 |
| [5] | Wang, Z., Jiang, L., Wang, J., Chai, Z. and Xiong, W. (2021) Morphine Promotes Angiogenesis by Activating PI3K/Akt/HIF-1α Pathway and Upregulating VEGF in Hepatocellular Carcinoma. Journal of Gastrointestinal Oncology, 12, 1761-1772. https://doi.org/10.21037/jgo-20-394 |
| [6] | Gu, F., Zhou, Y., Tian, L., Chen, J., Zhang, C., Huang, Z., et al. (2024) Morphine Promotes Non-Small Cell Lung Cancer Progression by Downregulating E-Cadherin via the PI3K/Akt/mTOR Pathway. Scientific Reports, 14, Article No. 21130. https://doi.org/10.1038/s41598-024-72198-1 |
| [7] | Bimonte, S., Barbieri, A., Cascella, M., Rea, D., Palma, G., Luciano, A., et al. (2019) Naloxone Counteracts the Promoting Tumor Growth Effects Induced by Morphine in an Animal Model of Triple-Negative Breast Cancer. In Vivo, 33, 821-825. https://doi.org/10.21873/invivo.11545 |
| [8] | Plein, L.M. and Rittner, H.L. (2018) Opioids and the Immune System—Friend or Foe. British Journal of Pharmacology, 175, 2717-2725. https://doi.org/10.1111/bph.13750 |
| [9] | 梁沛彰, 朱浩乾, 张小敏, 等. 吗啡对小鼠黑色素瘤的生长及免疫治疗效果的影响[J]. 中山大学学报(医学科学版), 2022, 43(6): 938-945. |
| [10] | Hou, M., Zhou, N., Li, H., Wang, B., Wang, X., Wang, X., et al. (2016) Morphine and Ketamine Inhibit Immune Function of Gastric Cancer Patients by Increasing Percentage of CD4+CD25+Foxp3+ Regulatory T Cells in Vitro. Journal of Surgical Research, 203, 306-312. https://doi.org/10.1016/j.jss.2016.02.031 |
| [11] | Jiang, Y., Li, T., Qian, Y., Zuo, X. and Liu, J. (2022) Morphine in Combination with Ketamine Improves Cervical Cancer Pain and Suppresses Immune Function via the JAK3/STAT5 Pathway. Pain Research and Management, 2022, Article ID: 9364365. https://doi.org/10.1155/2022/9364365 |
| [12] | Malik, J.A., Affan Khan, M., Lamba, T., Adeel Zafar, M., Nanda, S., Owais, M., et al. (2024) Immunosuppressive Effects of Morphine on Macrophage Polarization and Function. European Journal of Pharmacology, 975, Article 176637. https://doi.org/10.1016/j.ejphar.2024.176637 |
| [13] | Schmidt-Hansen, M., Bennett, M.I., Arnold, S., Bromham, N., Hilgart, J.S., Page, A.J., et al. (2022) Oxycodone for Cancer-Related Pain. Cochrane Database of Systematic Reviews, 6, Article No. CD003870. https://doi.org/10.1002/14651858.cd003870.pub7 |
| [14] | Tan, M., Wang, H., Gao, C., Jiang, Z., Yin, Y., Xing, R., Hu, L., Xu, J., Zhang, M. and Xie, Y. (2022) Erratum: Agonists Specific for κ-Opioid Receptor Induces Apoptosis of HCC Cells through Enhanced Endoplasmic Reticulum Stress. Frontiers in Oncology, 12, Article 844214. https://doi.org/10.3389/fonc.2022.937625 |
| [15] | Tian, M., Jin, L., Li, R., Zhu, S., Ji, M. and Li, W. (2016) Comparison of Oxycodone and Morphine on the Proliferation, Apoptosis and Expression of Related Molecules in the A549 Human Lung Adenocarcinoma Cell Line. Experimental and Therapeutic Medicine, 12, 559-566. https://doi.org/10.3892/etm.2016.3346 |
| [16] | Kokki, M., Pesonen, M., Vehviläinen, P., Litmala, O., Pasanen, M. and Kokki, H. (2016) Cytotoxicity of Oxycodone and Morphine in Human Neuroblastoma and Mouse Motoneuronal Cells: A Comparative Approach. Drugs in R&D, 16, 155-163. https://doi.org/10.1007/s40268-016-0125-0 |
| [17] | Yu, Y., Li, D., Duan, J., Xu, H., Li, L., Tan, D., et al. (2020) The Pro-and Anti-Cancer Effects of Oxycodone Are Associated with Epithelial Growth Factor Receptor Level in Cancer Cells. Bioscience Reports, 40, BSR20193524. https://doi.org/10.1042/bsr20193524 |
| [18] | Filipczak-Bryniarska, I., Nazimek, K., Nowak, B., Kozlowski, M., Wąsik, M. and Bryniarski, K. (2018) In Contrast to Morphine, Buprenorphine Enhances Macrophage-Induced Humoral Immunity and, as Oxycodone, Slightly Suppresses the Effector Phase of Cell-Mediated Immune Response in Mice. International Immunopharmacology, 54, 344-353. https://doi.org/10.1016/j.intimp.2017.11.039 |
| [19] | 田园, 杨海昌, 李秀华, 等. 羟考酮预处理对老龄脑缺血再灌注损伤大鼠的脑保护的作用[J]. 中国临床药理学杂志, 2023, 39(17): 2517-2521. |
| [20] | Hadley, G., Derry, S., Moore, R.A. and Wiffen, P.J. (2013) Transdermal Fentanyl for Cancer Pain. Cochrane Database of Systematic Reviews, 2018, Article No. CD010270. https://doi.org/10.1002/14651858.cd010270.pub2 |
| [21] | Xiao, K., Zheng, Q. and Bao, L. (2022) Fentanyl Activates Ovarian Cancer and Alleviates Chemotherapy-Induced Toxicity via Opioid Receptor-Dependent Activation of EGFR. BMC Anesthesiology, 22, Article No. 268. https://doi.org/10.1186/s12871-022-01812-4 |
| [22] | Liu, D. and Xu, S. (2023) Fentanyl Inhibits Cell Invasion and Migration by Modulating NF-κB Activation in Glioma. Brain Research, 1809, Article 148356. https://doi.org/10.1016/j.brainres.2023.148356 |
| [23] | Zhang, X.L., Chen, M.L. and Zhou, S.L. (2015) Fentanyl Inhibits Proliferation and Invasion of Colorectal Cancer via β-Catenin. International Journal of Clinical and Experimental Pathology, 8, 227-235. |
| [24] | Wang, D., Li, S., Ma, X., Chen, X., Tian, X., Li, X., et al. (2022) Immunomodulatory Effects of Fentanyl and Morphine on DSS-and TNBS-Induced Colitis. Immunopharmacology and Immunotoxicology, 44, 1044-1057. https://doi.org/10.1080/08923973.2022.2102993 |
| [25] | House, R.V., Thomas, P.T. and Bhargava, H.N. (1995) In Vitro Evaluation of Fentanyl and Meperidine for Immunomodulatory Activity. Immunology Letters, 46, 117-124. https://doi.org/10.1016/0165-2478(95)00035-4 |
| [26] | Kistemaker, K.R.J., Sijani, F., Brinkman, D.J., de Graeff, A., Burchell, G.L., Steegers, M.A.H., et al. (2024) Corrigendum to “Pharmacological Prevention and Treatment of Opioid-Induced Constipation in Cancer Patients: A Systematic Review and Meta-Analysis”. Cancer Treatment Reviews, 127, Article 102738. https://doi.org/10.1016/j.ctrv.2024.102738 |
| [27] | 张廷, 查安生. 中西医治疗阿片类药物相关性便秘研究进展[J]. 中国中医药图书情报杂志, 2024, 48(3): 249-253. |
| [28] | 田晓静, 黄冰, 刘艳丹. 九宫揉腹法在癌痛病人阿片类药物相关性便秘中的应用[J]. 循证护理, 2022, 8(19): 2679-2682. |
