Efficacy of systemic morphine suggests a fundamental difference in the mechanisms that generate bone cancer vs. inflammatory pain
Efficacy of systemic morphine suggests a fundamental difference in the mechanisms that generate bone cancer vs. inflammatory pain
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DOI：
10.1016/s0304-3959(02)00102-1
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发表时间：
2002-10-01
期刊：
影响因子：
7.4
通讯作者：
Mantyh, PW
中科院分区：
文献类型：
--
作者：
Luger, NM;Sabino, MAC;Mantyh, PW
疼痛是与癌症相关的事件，对癌症患者的生活质量影响最大。尽管骨癌疼痛是乳腺癌、前列腺癌和肺癌伴随的最严重和最常见的慢性疼痛之一，但人们对产生和维持这种疼痛的机制知之甚少。最近，我们开发了骨癌疼痛小鼠模型，在肿瘤植入股骨髓内间隙后 16 天，观察到明显的骨质破坏和骨癌疼痛相关行为。一个关键问题是这个模型与人类骨癌疼痛的反映有多接近。在本研究中，我们表明，与人类一样，系统性吗啡给药可以以剂量依赖的方式减少纳洛酮可逆的与疼痛相关的行为。与患有炎性疼痛的个体相比，患有骨癌疼痛的人类通常需要明显更高剂量的吗啡，并且在小鼠模型中，阻断骨癌疼痛相关行为所需的吗啡剂量是阻断由后爪注射完全弗氏佐剂（CFA）（1-3 mg/kg）诱导的同等程度的峰值炎症疼痛行为所需的吗啡剂量的十倍。由于这些动物接受了急性治疗，没有时间形成吗啡耐受性，并且在骨癌疼痛与炎性疼痛中观察到的镇痛功效向右移动，表明产生骨癌疼痛与炎性疼痛的潜在机制存在根本差异。这些结果表明，该模型可能有助于定义针对复杂骨癌疼痛综合征的药物疗法。 (C) 2002 年国际疼痛研究协会。由 Elsevier Science B.V. 出版。保留所有权利。
Pain is the cancer related event that is most disruptive to the cancer patient's quality of life. Although bone cancer pain is one of the most severe and common of the chronic pains that accompany breast, prostate and lung cancers, relatively little is known about the mechanisms that generate and maintain this pain. Recently, we developed a mouse model of bone cancer pain and 16 days following tumor implantation into the intramedullary space of the femur, significant bone destruction and bone cancer pain-related behaviors were observed. A critical question is how closely this model mirrors human bone cancer pain. In the present study we show that, as in humans, pain-related behaviors are diminished by systemic morphine administration in a dose dependent fashion that is naloxone-reversible. Humans suffering from bone cancer pain generally require significantly higher doses of morphine as compared to individuals with inflammatory pain and in the mouse model, the doses of morphine required to block bone cancer pain-related behaviors were ten times that required to block peak inflammatory pain behaviors of comparable magnitude induced by hindpaw injection of complete Freund's adjuvant (CFA) (1-3 mg/kg). As these animals were treated acutely, there was not time for morphine tolerance to develop and the rightward shift in analgesic efficacy observed in bone cancer pain vs. inflammatory pain suggests a fundamental difference in the underlying mechanisms that generate bone cancer vs. inflammatory pain. These results indicate that this model may be useful in defining drug therapies that are targeted for complex bone cancer pain syndromes. (C) 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.