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1.湖南中医药大学,长沙 410208
2.湖南中医药大学 第一附属医院,长沙 410007
3.湖南省中医药研究院 附属医院,长沙 410006
Published:05 June 2023,
Published Online:18 August 2022,
Received:19 April 2022,
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赖桂花,王菲,聂多锐等.骨转移癌痛发病机制及中医药防治研究进展[J].中国实验方剂学杂志,2023,29(11):231-239.
LAI Guihua,WANG Fei,NIE Duorui,et al.Pathogenesis of Bone Metastasis-caused Pain and Its Prevention and Treatment with Traditional Chinese Medicine: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(11):231-239.
赖桂花,王菲,聂多锐等.骨转移癌痛发病机制及中医药防治研究进展[J].中国实验方剂学杂志,2023,29(11):231-239. DOI: 10.13422/j.cnki.syfjx.202202026.
LAI Guihua,WANG Fei,NIE Duorui,et al.Pathogenesis of Bone Metastasis-caused Pain and Its Prevention and Treatment with Traditional Chinese Medicine: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(11):231-239. DOI: 10.13422/j.cnki.syfjx.202202026.
骨转移癌痛是癌症最常见的并发症之一,其发病率随着癌症总体患病率增加而逐年升高,严重影响癌症患者的生活质量及生存期。骨转移癌痛是一种同时具备炎性疼痛和神经病理性疼痛特征而又异于2种类型的特殊疼痛,因此其发病机制非常复杂,深入了解其发病机制具有十分重要的意义。目前骨转移癌痛发病机制的研究多集中在破骨细胞活化、骨微环境的变化、胶质细胞活化、脊髓神经元活化、微小RNA失调等方面。现代医学治疗骨转移癌痛以三阶梯止痛药物、双膦酸盐类药物、骨转移灶的姑息性放疗及介入治疗为主,短期止痛疗效确切,但由于其不良作用、成瘾性及耐药性等问题未获得满意的长期疗效。研究表明中医药治疗骨转移癌痛有确切的疗效,不仅具有安全性高、增效减毒、增强患者免疫力等优点,而且可通过多成分、多靶点及多通路发挥协同治疗的作用,使其在防治骨转移癌痛方面具有独特的优势,成为众医家学者的研究重点。该文系统整理了近年国内外文献库中有关骨转移癌痛发病机制及中医药(中药复方、单药及单体)干预的研究文献,将从抑制破骨细胞活化、胶质细胞活化及脊髓神经元活化、调控疼痛介质及微小RNA异常表达及抗肿瘤等方面详细综述,以期进一步阐明骨转移癌痛的发病机制,并为中医药有效防治骨转移癌痛提供更全面的思路与方法。
Bone metastasis-caused pain (BMP) is a common complication of cancer, and the incidence has been on the rise with the increase in the overall prevalence of cancer, threatening the survival and quality of life of patients. BMP is a kind of special pain with the characteristics of inflammatory pain and neuropathic pain, but is different from the two. Therefore, its pathogenesis is very complicated, and it is of great significance to understand the pathogenesis. The currently available studies mainly focused on osteoclast activation, changes in the bone microenvironment, glial cell activation, spinal cord neuron activation, and miRNA dysregulation. Modern therapies include the three-step analgesics, bisphosphonates, palliative radiotherapy, and interventional therapy for bone metastases, which show definite efficacy in short term. However, the long-term effect is unsatisfactory due to the adverse reactions, addiction, and drug resistance. Studies have shown that traditional Chinese medicine (TCM) has definite curative effect on BMP, which is safe, enhances efficacy, reduces toxicity, and boosts immunity. Moreover, it exerts the effect through multiple components, multiple targets, and multiple pathways. As a result, it has unique advantages in the prevention and treatment of BMP and has become a research focus. This paper summarizes the research on the pathogenesis of BMP, the intervention of TCM (compound Chinese medicine prescriptions, Chinese medicinals, and monomers from Chinese medicinals), and the mechanisms of TCM, such as inhibiting osteoclast activation, glial cell activation, and spinal cord neuron activation, regulating pain mediators and abnormal expression of microRNA, and anti-tumor, which is expected to further clarify the pathogenesis of BMP and provide ideas and methods for the effective prevention and treatment of BMP with TCM.
骨转移癌痛发病机制中医药研究进展
bone metastasis-caused painpathogenesistraditional Chinese medicineresearch progress
FORNETTI J, WELM A L, STEWART S A. Understanding the bone in cancer metastasis[J]. J Bone Miner Res, 2018,33(12):2099-2113.
ZAJĄCZKOWSKA R, KOCOT-KĘPSKA M, LEPPERT W, et al. Bone pain in cancer patients: Mechanisms and current treatment[J]. Int J Mol Sci, 2019,20(23) :6047.
SWARM R A, PAICE J A, ANGHELESCU D L, et al. Adult cancer pain, version 3.2019, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2019,17(8):977-1007.
KAPOOR R, SAXENA A K, VASUDEV P, et al. Cancer induced bone pain: Current management and future perspectives[J]. Med Oncol, 2021,38(11):134.
HUA B, GAO Y, KONG X, et al. New insights of nociceptor sensitization in bone cancer pain[J]. Expert Opin Ther Targets, 2015,19(2):227-243.
杜俊英, 房军帆, 梁宜, 等. 基于脊髓层面的骨癌痛发生机制[J]. 中国肿瘤,2014,23(10):849-853.
VON MOOS R, COSTA L, RIPAMONTI C I, et al. Improving quality of life in patients with advanced cancer: Targeting metastatic bone pain[J]. Eur J Cancer, 2017,71:80-94.
GADEPALLI A, AKHILESH, UNIYAL A, et al. Multifarious targets and recent developments in the therapeutics for the management of bone cancer pain[J]. ACS Chem Neurosci, 2021,12(22):4195-4208.
NAFZIGER A N, BARKIN R L. Opioid therapy in acute and chronic pain[J]. J Clin Pharmacol, 2018,58(9):1111-1122.
VARGAS-FRANCO J W, CASTANEDA B, RÉDINÍ F, et al. Paradoxical side effects of bisphosphonates on the skeleton: What do we know and what can we do?[J]. J Cell Physiol, 2018,233(8):5696-5715.
FANG J, XU Q. Differences of osteoblastic bone metastases and osteolytic bone metastases in clinical features and molecular characteristics[J]. Clin Transl Oncol, 2015,17(3):173-179.
SCHWEI M J, HONORE P, ROGERS S D, et al. Neurochemical and cellular reorganization of the spinal cord in a murine model of bone cancer pain[J]. J Neurosci, 1999,19(24):10886-10897.
GONZÁLEZ-SUÁREZ E, SANZ-MORENO A. RANK as a therapeutic target in cancer[J]. FEBS J, 2016,283(11):2018-2033.
李昌龙. 破骨细胞活化在骨癌痛中作用机制的研究进展[J]. 世界最新医学信息文摘,2017,17(5):11.
FENG X, TEITELBAUM S L. Osteoclasts: New insights[J]. Bone Res, 2013,1(1):11-26.
王家辉, 蒋林兰, 沈赞. 乳腺癌骨转移研究的新进展及展望——从机制到临床[J]. 中国癌症杂志,2022,32(2):172-176.
邓宇琳, 王菊勇, 蔡婷婷. OPG-RANKL-RANK系统与骨癌痛的研究进展[J]. 现代肿瘤医学,2017,25(24):4079-4082.
PANG X, GONG K, ZHANG X, et al. Osteopontin as a multifaceted driver of bone metastasis and drug resistance[J]. Pharmacol Res, 2019,144:235-244.
HOFBAUER L C, BOZEC A, RAUNER M, et al. Novel approaches to target the microenvironment of bone metastasis[J]. Nat Rev Clin Oncol, 2021,18(8):488-505.
QIN A, CHENG T S, PAVLOS N J, et al. V-ATPases in osteoclasts: Structure, function and potential inhibitors of bone resorption[J]. Int J Biochem Cell Biol, 2012,44(9):1422-1435.
NERI D, SUPURAN C T. Interfering with pH regulation in tumours as a therapeutic strategy[J]. Nat Rev Drug Discov, 2011,10(10):767-777.
周佳宏, 李民. 肿瘤微环境在骨癌痛中作用的新进展[J]. 基础医学与临床,2021,41(3):448-451.
WU W L, CHENG C F, SUN W H, et al. Targeting ASIC3 for pain, anxiety, and insulin resistance[J]. Pharmacol Ther, 2012,134(2):127-138.
HO K W, WARD N J, CALKINS D J. TRPV1: A stress response protein in the central nervous system[J]. Am J Neurodegener Dis, 2012,1(1):1-14.
YONEDA T, HIASA M, NAGATA Y, et al. Contribution of acidic extracellular microenvironment of cancer-colonized bone to bone pain[J]. Biochim Biophys Acta, 2015,1848(10 Pt B):2677-2684.
HIRAGA T. Bone metastasis: Interaction between cancer cells and bone microenvironment[J]. J Oral Biosci, 2019,61(2):95-98.
WOOLF C J, SALTER M W. Neuronal plasticity: Increasing the gain in pain[J]. Science, 2000,288(5472):1765-1769.
ZHAI M, YANG S, LIN S, et al. Distinct gene expression patterns of ion channels and cytokines in rat primary sensory neurons during development of bone cancer and cancer pain[J]. Front Mol Neurosci, 2021, doi: 10.3389/fnmol.2021.665085http://dx.doi.org/10.3389/fnmol.2021.665085.
施任怡, 蔡杨乾, 杜俊英, 等. P2X受体在骨癌痛发生和维持中的作用及其机制探讨[J]. 中国疼痛医学杂志,2018,24(8):623-627.
KUDO K, TAKAHASHI T, SUZUKI S. The changes of c-Fos expression by motor cortex stimulation in the deafferentation pain model[J]. Neurol Med Chir (Tokyo), 2014,54(7):537-544.
李琪琪, 林健清. 小胶质细胞活化参与骨癌痛机制的研究进展[J]. 中国疼痛医学杂志,2020,26(9):685-688.
刘思兰, 杨建平, 王丽娜,等. 骨癌痛大鼠脊髓NF-κB、IL-6和TNF-α表达的变化[J]. 中华麻醉学杂志,2010,30(9):1030-1033.
李秋月, 许海玉, 杨洪军. 促炎因子TNF-α,IL-1β,IL-6在神经病理性疼痛中的研究进展[J]. 中国中药杂志,2017,42(19):3709-3712.
FANG D, KONG L Y, CAI J, et al. Interleukin-6-mediated functional upregulation of TRPV1 receptors in dorsal root ganglion neurons through the activation of JAK/PI3K signaling pathway: Roles in the development of bone cancer pain in a rat model[J]. Pain, 2015,156(6):1124-1144.
GUAN X H, FU Q C, SHI D, et al. Activation of spinal chemokine receptor CXCR3 mediates bone cancer pain through an Akt-ERK crosstalk pathway in rats[J]. Exp Neurol, 2015,263:39-49.
ZHU H Y, LIU X, MIAO X, et al. Up-regulation of CXCR4 expression contributes to persistent abdominal pain in rats with chronic pancreatitis[J]. Mol Pain, 2017, doi:10.1177/1744806917697979http://dx.doi.org/10.1177/1744806917697979.
ZHOU Y Q, GAO H Y, GUAN X H, et al. Chemokines and their receptors: Potential therapeutic targets for bone cancer pain[J]. Curr Pharm Des, 2015,21(34):5029-5033.
鲁莹, 李勃, 王蓉, 等. 趋化因子及其受体参与癌痛的研究进展[J]. 中国病理生理杂志,2022,38(2):364-369.
HU J H, YANG J P, LIU L, et al. Involvement of CX3CR1 in bone cancer pain through the activation of microglia p38 MAPK pathway in the spinal cord[J]. Brain Res, 2012, doi:10.1016/j.brainres.2012.05.020http://dx.doi.org/10.1016/j.brainres.2012.05.020.
薛松, 孙涛. 小胶质细胞介导脊髓损伤后神经病理性疼痛机制研究进展[J]. 中国疼痛医学杂志,2022,28(3):165-172.
MILLER Y I, NAVIA-PELAEZ J M, CORR M, et al. Lipid rafts in glial cells: Role in neuroinflammation and pain processing[J]. J Lipid Res, 2020,61(5):655-666.
王振鹏, 王开强. 星形胶质细胞和小胶质细胞介导的神经病理痛研究进展[J]. 现代中西医结合杂志,2017,26(10):1134-1137.
JUN C, XIUFENG C, XIUZHU Z, et al. Effects of parecoxib on pain threshold and inflammatory factors IL-1β, IL-6 and TNF-α in spinal cord of rats with bone cancer pain[J]. J Coll Physicians Surg Pak, 2019,29(6): 528-531.
ZHOU K X, HE X T, HU X F, et al. XPro1595 ameliorates bone cancer pain in rats via inhibiting p38-mediated glial cell activation and neuroinflammation in the spinal dorsal horn[J]. Brain Res Bull, 2019,149:137-147.
MAO-YING Q L, WANG X W, YANG C J, et al. Robust spinal neuroinflammation mediates mechanical allodynia in Walker 256 induced bone cancer rats[J]. Mol Brain, 2012, doi:10.1186/1756-6606-5-16http://dx.doi.org/10.1186/1756-6606-5-16.
HUANG Z X, 张钰. 延髓头端腹内侧区的P2X7受体参与骨癌痛:下行易化机制[J]. 中国疼痛医学杂志,2015,21(1):9.
DONOVAN-RODRIGUEZ T, URCH C E, DICKENSON A H. Evidence of a role for descending serotonergic facilitation in a rat model of cancer-induced bone pain[J]. Neurosci Lett, 2006,393(2/3):237-242.
CHIOU C S, HUANG C C, LIANG Y C, et al. Impairment of long-term depression in the anterior cingulate cortex of mice with bone cancer pain[J]. Pain, 2012,153(10):2097-2108.
卫世有, 杭黎华. 微RNA参与骨癌痛的研究进展[J]. 国际麻醉学与复苏杂志,2020,41(3):311-314.
BALI K K, SELVARAJ D, SATAGOPAM V P, et al. Genome-wide identification and functional analyses of microRNA signatures associated with cancer pain[J]. EMBO Mol Med, 2013,5(11):1740-1758.
MEI H X, ZHOU M H, ZHANG X W, et al. Effects of miR-338 on morphine tolerance by targeting CXCR4 in a rat model of bone cancer pain[J]. Biosci Rep, 2017,37(2) :BSR20160517.
ZHANG X H, GENG G L, SU B, et al. MicroRNA-338-3p inhibits glucocorticoid-induced osteoclast formation through RANKL targeting[J]. Genet Mol Res, 2016,15(3) :10.4238/gmr.15037674.
HOU B, CUI X, LIU Y, et al. Positive feedback regulation between microRNA-132 and CREB in spinal cord contributes to bone cancer pain in mice[J]. Eur J Pain, 2016,20(8):1299-1308.
和秋莉. 内质网应激活化caspase依赖性凋亡通路参与骨癌痛机制研究[D].蚌埠: 蚌埠医学院,2020.
陈淑萍. 自噬激活缓解大鼠骨癌痛的机制研究[D].武汉: 华中科技大学,2020.
陆翠娥. CB2受体激动剂通过调节脊髓自噬水平影响星型胶质细胞参与调控大鼠骨癌痛[D].南京: 南京大学,2016.
周雪蓉. 活性氧清除剂缓解大鼠骨癌痛的作用机制研究[D].武汉: 华中科技大学,2020.
马玥, 王立芳, 徐振晔. 中医药治疗骨转移癌痛的研究进展[J]. 世界科学技术—中医药现代化,2018,20(3):468-472.
陈健琳. 骨转移癌痛的中医药治疗进展[J]. 中国中医药现代远程教育,2017,15(5):136-139.
徐志红. 张晓春教授治疗骨转移性癌痛的临床经验总结[D].南京: 南京中医药大学,2016.
赖桂花, 袁晶, 闫钰婷, 等. 骨转移癌痛的中西医治疗进展[J]. 湖南中医药大学学报,2019,39(9):1166-1170.
LI Z, XIAO J, WU X, et al. Plumbagin inhibits breast tumor bone metastasis and osteolysis by modulating the tumor-bone microenvironment[J]. Curr Mol Med, 2012,12(8):967-981.
SULTANLI S, GHUMNANI S, ASHMA R, et al. Plumbagin, a biomolecule with (Anti)osteoclastic properties[J]. Int J Mol Sci, 2021,22(5):2779.
SHEN X, SUN X, CHEN H, et al. Demethoxycucumin protects MDA-MB-231 cells induced bone destruction through JNK and ERK pathways inhibition[J]. Cancer Chemother Pharmacol, 2021,87(4):487-499.
贺龙刚, 高奥, 邱煌沛, 等. 淫羊藿次苷Ⅰ及其代谢产物淫羊藿次苷Ⅱ通过AP-1/NFATc1信号通路调控破骨细胞生成[J]. 中华中医药杂志,2017,32(3):1299-1302.
曾华倩. 基于CB2受体探讨华蟾素在骨癌痛中的应用[D].宜昌: 三峡大学,2021.
宋洪丽. 益肾骨康方抑制骨癌痛的作用机制及成药性研究[D].北京: 中国中医科学院,2019.
赫锦锦, 方东. 徐长卿丹皮酚对骨癌痛大鼠镇痛作用的研究[J]. 中国药理学通报,2020,36(11):1526-1531.
朱时钰, 刘丹, 陆永利, 等. 华蟾素对骨癌痛模型大鼠背根神经节细胞L型电压门控钙通道电流的影响[J]. 中国病理生理杂志,2019,35(10):1889-1893,1920.
朱时钰, 刘丹, 胡卫, 等. 华蟾素对骨癌痛大鼠背根神经节细胞瞬时外向钾通道电流的影响[J]. 南方医科大学学报,2019,39(9):1078-1082.
高哲健祎, 谢开宇, 徐义勇, 等. 蛇床子素对骨癌痛大鼠的镇痛作用及对TLR4/NF-κB信号通路的影响[J]. 中医药导报,2022,28(1):25-30.
周婷婷. rBmK-AGAP通过抑制星形胶质细胞内NF-κB信号通路减轻大鼠骨癌痛的研究[D].大连: 大连医科大学,2019.
HUANG Q, MAO X F, WU H Y, et al. Bullatine A stimulates spinal microglial dynorphin A expression to produce anti-hypersensitivity in a variety of rat pain models[J]. J Neuroinflammation, 2016,13(1):214.
金慧丹. 全蝎对骨癌痛大鼠痛行为及脊髓星形胶质细胞和小胶质细胞活化影响的研究[D].大连: 大连医科大学,2018.
YU J, LUO Y, JIN H, et al. Scorpion alleviates bone cancer pain through inhibition of bone destruction and glia activation[J]. Mol Pain, 2020, doi:10.1177/1744806920909993http://dx.doi.org/10.1177/1744806920909993.
HAO M, TANG Q, WANG B, et al. Resveratrol suppresses bone cancer pain in rats by attenuating inflammatory responses through the AMPK/Drp1 signaling[J]. Acta Biochim Biophys Sin (Shanghai), 2020,52(3):231-240.
张斌, 魏冬梅, 卞尧尧, 等. 芷辛方对骨癌痛大鼠胶质细胞蛋白表达及核因子κB的影响[J]. 中医杂志,2015,56(2):148-151.
张斌, 孙松娴, 陈轶尘, 等. 中药芷辛方对骨癌痛大鼠胶质细胞蛋白表达以及TLRs和NF-κB的影响[J]. 中国中西医结合杂志,2015,35(6):704-711.
刘丹, 张文, 王心怡, 等. 华蟾素对骨癌痛大鼠的镇痛效应及对脊髓胶质细胞活化的影响[J]. 癌变·畸变·突变,2018,30(4):302-306.
王心怡, 曾华倩, 胡卫. 华蟾素通过抑制脊髓CCL2/CCR2途径及小胶质细胞的活化缓解骨癌痛[J]. 药学学报,2020,55(1):67-73.
刘丹, 焦良波, 陈涛, 等. 基于对骨癌痛大鼠脊髓TAK1/JNK/c-Jun信号通路的调控探讨华蟾素镇痛机制[J]. 中国药学杂志,2021,56(2):108-114.
王玉, 刘胜, 宋晓耘, 等. 乳腺术后骨转方对骨癌痛大鼠疼痛行为及脊髓星形胶质细胞活化影响[J]. 辽宁中医药大学学报,2017,19(6):33-36.
任炳旭, 马正良, 靳艳卿, 等. 身痛逐瘀汤对骨癌痛小鼠痛行为及脊髓星形胶质细胞活化的影响[J]. 中国中西医结合杂志,2011,31(3):381-385.
孙萍萍, 俞忠明, 余平. 独活寄生汤对骨癌痛小鼠痛行为及脊髓星形胶质细胞GFAP表达的影响[J]. 中华中医药学刊,2016,34(2):387-390.
陈训春, 李名兰, 潘碧云, 等. 抗癌痛方对肺癌骨痛小鼠的作用机制及对症因子的影响[J]. 世界中西医结合杂志,2021,16(10):1826-1830.
张莹, 王志国, 欧阳竞锋, 等. CQ复方对骨癌痛模型大鼠的痛觉敏化干预作用及机制[J]. 中国实验方剂学杂志,2017,23(22):119-124.
何佩珊, 冯兴中, 姜敏, 等. 香辛方外敷对肺癌骨癌痛小鼠炎性介质和MCP-1的影响[J]. 中国中西医结合外科杂志,2019,25(3):262-266.
路凯, 白宁, 陈方, 等. 甘草酸治疗对骨癌痛小鼠痛行为及脊髓炎症反应的影响[J]. 现代肿瘤医学,2021,29(13):2249-2253.
罗琴琴, 王立芳, 徐振晔, 等. 骨痛灵方对肺癌骨癌痛模型小鼠的疼痛行为学以及脊髓MCP-1和NGF的影响[J]. 上海中医药杂志,2017,51(2):81-84.
郑晓霞, 陈文瑛, 张群, 等. 华蟾素对胫骨癌痛大鼠机械痛敏的作用及其机制的研究[J]. 今日药学,2018,28(9):580-583.
焦良波, 刘丹, 陈涛, 等. 华蟾素对骨癌痛大鼠镇痛机制探讨[J]. 中草药,2020,51(14):3734-3741.
黄杰, 秦刚, 柯辉雄, 等. 化瘀镇痛方联合氯化锶治疗骨转移性癌痛临床研究[J]. 新中医,2022,54(3):147-151.
焦美, 雷建军, 张志成, 等. 丹皮酚调控miR-21对骨癌痛大鼠的镇痛作用及对MAPK信号通路的影响[J]. 解剖科学进展,2021,27(4):453-457.
邹环球. 参苓白术散加味对骨癌痛小鼠AKT、P70S6的影响研究[D].南宁: 广西中医药大学,2019.
赖雅文. 参苓白术散加味对骨癌痛小鼠VEGF、mTOR通路相关蛋白的影响研究[D]. 南宁: 广西中医药大学,2019.
张志辉, 徐俊, 柯建辉, 等. 鞘内注射白藜芦醇对骨癌痛大鼠脊髓背角神经元CaMKⅡ活化的影响[J]. 中华麻醉学杂志,2015,35(1):68-71.
郑炜, 张秋芳, 李洪刚. 白藜芦醇对骨癌痛大鼠的镇痛作用及对内质网应激通路的影响[J]. 中医药导报,2020,26(16):18-22.
HAILI Z, JIEQIONG D, JI W, et al. Resveratrol attenuates bone cancer pain through regulating the expression levels of ASIC3 and activating cell autophagy[J]. Acta Biochim Biophys Sin (Shanghai), 2017,49(11) :1008-1014.
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