Angiotensin-(1-7)/Mas receptor as an antinociceptive agent in cancer-induced bone pain.
Angiotensin-(1-7)/Mas receptor as an antinociceptive agent in cancer-induced bone pain.
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血管紧张素 - （1-7）/MAS受体作为癌症引起的骨痛的抗伤害感受剂。
DOI：
10.1097/j.pain.0000000000000690
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发表时间：
2016-12
期刊：
影响因子：
7.4
通讯作者：
Vanderah TW
中科院分区：
文献类型：
--
作者：
Forte BL;Slosky LM;Zhang H;Arnold MR;Staatz WD;Hay M;Largent-Milnes TM;Vanderah TW
我们的数据表明，Ang-（1-7）/MasR激活可显著减轻癌症引起的骨痛，可能是晚期癌症患者的辅助镇痛药，无副作用。许多癌性实体瘤转移到骨并引起疼痛（癌症引起的骨痛[CIBP]）。癌症引起的骨痛通常是严重的，因为炎症增强，骨降解迅速，疾病进展。阿片类药物是用来治疗这种疼痛的，但它们可能会增加骨质流失和增加肿瘤增殖，进一步影响患者的生活质量。血管紧张素-（1-7）（Ang-（1-7））结合并激活Mas受体（MasR）。血管紧张素-（1-7）/MasR激活调节急性组织损伤后的炎症信号传导，但没有研究调查Ang-（1-7）/MasR是否在CIBP中起作用。我们假设Ang-（1-7）通过靶向乳腺CIBP小鼠模型中的MasR来抑制CIBP。66.1将乳腺癌细胞植入作为CIBP模型的BALB/cAnNHsd小鼠的股骨中。在急性和慢性施用Ang-（1-7）之前和之后评估自发性和诱发性疼痛行为。从动物收集组织用于MasR表达、肿瘤负荷和骨完整性的离体分析。癌症接种增加了自发性疼痛行为，在第7天，在单次注射Ang-（1-7）后和持续给药后显著降低。预先给予A-779（一种选择性MasR拮抗剂）可阻止这种减少，而预先给予AT 2拮抗剂则无此作用; AT 1拮抗剂可增强CIBP中Ang-（1-7）的抗伤害活性。重复给予Ang-（1-7）并没有显著改变肿瘤负荷或骨重建。这里的数据表明，Ang-（1-7）/MasR激活显著减弱CIBP，同时缺乏阿片类药物的许多副作用。因此，Ang-（1-7）可能是近90%经历剧烈疼痛的晚期癌症患者的替代治疗策略。
Our data suggest that Ang-(1-7)/MasR activation significantly attenuates cancer-induced bone pain and may be an adjunct analgesic for patients with advanced-stage cancer without side effects. Many cancerous solid tumors metastasize to the bone and induce pain (cancer-induced bone pain [CIBP]). Cancer-induced bone pain is often severe because of enhanced inflammation, rapid bone degradation, and disease progression. Opioids are prescribed to manage this pain, but they may enhance bone loss and increase tumor proliferation, further compromising patient quality of life. Angiotensin-(1-7) (Ang-(1-7)) binds and activates the Mas receptor (MasR). Angiotensin-(1-7)/MasR activation modulates inflammatory signaling after acute tissue insult, yet no studies have investigated whether Ang-(1-7)/MasR play a role in CIBP. We hypothesized that Ang-(1-7) inhibits CIBP by targeting MasR in a murine model of breast CIBP. 66.1 breast cancer cells were implanted into the femur of BALB/cAnNHsd mice as a model of CIBP. Spontaneous and evoked pain behaviors were assessed before and after acute and chronic administration of Ang-(1-7). Tissues were collected from animals for ex vivo analyses of MasR expression, tumor burden, and bone integrity. Cancer inoculation increased spontaneous pain behaviors by day 7 that were significantly reduced after a single injection of Ang-(1-7) and after sustained administration. Preadministration of A-779 a selective MasR antagonist prevented this reduction, whereas pretreatment with the AT2 antagonist had no effect; an AT1 antagonist enhanced the antinociceptive activity of Ang-(1-7) in CIBP. Repeated Ang-(1-7) administration did not significantly change tumor burden or bone remodeling. Data here suggest that Ang-(1-7)/MasR activation significantly attenuates CIBP, while lacking many side effects seen with opioids. Thus, Ang-(1-7) may be an alternative therapeutic strategy for the nearly 90% of patients with advanced-stage cancer who experience excruciating pain.
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影响因子：
7.3
作者：
BLANKLEY, CJ;HODGES, JC;COHEN, DM
通讯作者：
COHEN, DM
影响因子：
3.1
作者：
Costa, Aline C. O.;Becker, Lenice K.;Duarte, Igor D. G.
通讯作者：
Duarte, Igor D. G.
影响因子：
15.1
作者：
Hutchinson, Mark R.;Zhang, Yingning;Shridhar, Mitesh;Evans, John H.;Buchanan, Madison M.;Zhao, Tina X.;Slivka, Peter F.;Coats, Benjamen D.;Rezvani, Niloofar;Wieseler, Julie;Hughes, Travis S.;Landgraf, Kyle E.;Chan, Stefanie;Fong, Stephanie;Phipps, Simon;Falke, Joseph J.;Leinwand, Leslie A.;Maier, Steven F.;Yin, Hang;Rice, Kenner C.;Watkins, Linda R.
通讯作者：
Watkins, Linda R.
DOI：
10.1016/j.jpain.2014.09.010
发表时间：
2014-12
期刊：
The journal of pain
影响因子：
--
作者：
Goswami SC;Mishra SK;Maric D;Kaszas K;Gonnella GL;Clokie SJ;Kominsky HD;Gross JR;Keller JM;Mannes AJ;Hoon MA;Iadarola MJ
通讯作者：
Iadarola MJ
影响因子：
8.3
作者：
Inagami, T
通讯作者：
Inagami, T