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镇痛药对前列腺癌骨转移小鼠模型中肿瘤生长的影响。

Effects of Analgesics on Tumor Growth in Mouse Models of Prostate Cancer Bone Metastasis.

机构信息

Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan; Division of Animal Resources, University of Illinois at Urbana-Champaign, Urbana, Illinois; Refinement Enrichment Advancements Laboratory, Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan; Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan;, Email:

Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan; Refinement Enrichment Advancements Laboratory, Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan.

出版信息

J Am Assoc Lab Anim Sci. 2021 May 1;60(3):341-348. doi: 10.30802/AALAS-JAALAS-20-000060. Epub 2021 May 3.

DOI:10.30802/AALAS-JAALAS-20-000060
PMID:33952382
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8145123/
Abstract

Murine models of tumor development often require invasive procedures for tumor implantation, potentially causing pain or distress. However, analgesics are often withheld during implantation because of concerns that they may adversely affect tumor development. Previous studies examining the effects of analgesics on the development and metastasis of various tumor lines show that the effect of analgesics depends on the tumor line and analgesic used. A blanket statement that analgesics affect the general growth of tumors is not adequate scientific justification for withholding pain relief, and pilot studies or references are recommended for each specific tumor cell line and treatment combination. In this study, we evaluated the effects of 2 commonly used analgesics on tumor growth in 2 models of prostate cancer (PCa) bone metastasis. We hypothesized that a one-time injection of analgesics at the time of intratibial injection of tumor cells would not significantly impact tumor growth. Either C57BL/6 or SCID mice were injected subcutaneously with an analgesic (carprofen [5 mg/kg], or buprenorphine [0.1 mg/kg]) or vehicle (0.1 mL of saline) at the time of intratibial injection with a PCa cell line (RM1 or PC3, = 10 to 11 per group). Tumor growth (measured by determination of tumor burden and the extent of bone involvement) and welfare (measured by nociception, locomotion, and weight) were monitored for 2 to 4 wk. Neither carprofen or buprenorphine administration consistently affected tumor growth or indices of animal welfare as compared with the saline control for either cell line. This study adds to the growing body of literature demonstrating that analgesia can be compatible with scientific objectives, and that a decision to withhold analgesics must be scientifically justified and evaluated on a model-specific basis.

摘要

肿瘤发展的鼠模型通常需要进行肿瘤植入的侵入性程序,这可能会引起疼痛或不适。然而,由于担心它们可能会对肿瘤的发展产生不利影响,在植入过程中通常会避免使用止痛药。以前的研究检查了止痛药对各种肿瘤系的发展和转移的影响,结果表明止痛药的作用取决于肿瘤系和使用的止痛药。不能将止痛药普遍影响肿瘤生长的说法作为不提供止痛的充分科学理由,建议针对每个特定的肿瘤细胞系和治疗组合进行初步研究或参考。在这项研究中,我们评估了两种常用止痛药在两种前列腺癌(PCa)骨转移模型中的肿瘤生长的影响。我们假设在肿瘤细胞经胫骨内注射时进行一次止痛药注射不会对肿瘤生长产生显著影响。C57BL/6 或 SCID 小鼠在胫骨内注射 PCa 细胞系(RM1 或 PC3)时,皮下注射止痛药(卡洛芬[5mg/kg]或丁丙诺啡[0.1mg/kg])或载体(0.1mL 生理盐水)(每组 n=10-11)。监测肿瘤生长(通过确定肿瘤负担和骨受累程度来衡量)和福利(通过疼痛、运动和体重来衡量)2-4 周。与生理盐水对照相比,卡洛芬或丁丙诺啡给药均未一致影响两种细胞系的肿瘤生长或动物福利指标。这项研究增加了越来越多的文献,证明了镇痛可以与科学目标兼容,并且必须根据具体的模型对拒绝使用镇痛药的决定进行科学论证和评估。

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本文引用的文献

1
Intraperitoneal Route of Drug Administration: Should it Be Used in Experimental Animal Studies?腹腔内给药途径:在实验动物研究中是否应该使用?
Pharm Res. 2019 Dec 23;37(1):12. doi: 10.1007/s11095-019-2745-x.
2
Nonsteroidal anti-inflammatory drugs and pain in cancer patients: a systematic review and reappraisal of the evidence.非甾体抗炎药与癌症患者的疼痛:系统评价与证据再评估。
Br J Anaesth. 2019 Aug;123(2):e412-e423. doi: 10.1016/j.bja.2019.02.028. Epub 2019 May 20.
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Models of Prostate Cancer Bone Metastasis.前列腺癌骨转移模型
Methods Mol Biol. 2019;1914:295-308. doi: 10.1007/978-1-4939-8997-3_16.
4
Bone biopsy in nephrology practice.肾脏病学实践中的骨活检
J Bras Nefrol. 2018 Oct-Dec;40(4):366-374. doi: 10.1590/2175-8239-jbn-2017-0012. Epub 2018 Nov 29.
5
Perioperative Immunosuppression and Risk of Cancer Progression: The Impact of Opioids on Pain Management.围手术期免疫抑制与癌症进展风险:阿片类药物对疼痛管理的影响。
Pain Res Manag. 2018 Sep 19;2018:9293704. doi: 10.1155/2018/9293704. eCollection 2018.
6
Acclimation and Institutionalization of the Mouse Microbiota Following Transportation.运输后小鼠微生物群的适应与定植
Front Microbiol. 2018 May 28;9:1085. doi: 10.3389/fmicb.2018.01085. eCollection 2018.
7
Analgesic Efficacy and Hematologic Effects of Robenacoxib in Mice.罗非昔布在小鼠中的镇痛疗效和血液学影响。
J Am Assoc Lab Anim Sci. 2018 May 1;57(3):258-267.
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Using Cageside Measures to Evaluate Analgesic Efficacy in Mice () after Surgery.使用笼边测量法评估小鼠术后镇痛效果()
J Am Assoc Lab Anim Sci. 2018 Mar 1;57(2):186-201.
9
Establishment and characterization of in vivo orthotopic bioluminescent xenograft models from human osteosarcoma cell lines in Swiss nude and NSG mice.在瑞士裸鼠和 NSG 小鼠体内建立和鉴定人成骨肉瘤细胞系的原位生物发光异种移植模型。
Cancer Med. 2018 Mar;7(3):665-676. doi: 10.1002/cam4.1346. Epub 2018 Feb 23.
10
To Treat or Not to Treat: The Effects of Pain on Experimental Parameters.治疗还是不治疗:疼痛对实验参数的影响。
Comp Med. 2017 Dec 1;67(6):469-482.