Blockade of nerve sprouting and neuroma formation markedly attenuates the development of late stage cancer pain.
Blockade of nerve sprouting and neuroma formation markedly attenuates the development of late stage cancer pain.
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DOI：
10.1016/j.neuroscience.2010.08.056
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发表时间：
2010-12-01
期刊：
影响因子：
3.3
通讯作者：
Mantyh PW
中科院分区：
文献类型：
--
作者：
Mantyh WG;Jimenez-Andrade JM;Stake JI;Bloom AP;Kaczmarska MJ;Taylor RN;Freeman KT;Ghilardi JR;Kuskowski MA;Mantyh PW
对于许多患者来说，疼痛是癌症的第一个迹象，虽然疼痛可以在任何时候出现，但疼痛的频率和强度往往会随着疾病的进展而增加。因此，75%至90%的转移性或晚期癌症患者将经历显著的癌症引起的疼痛。一个主要的未回答的问题是，为什么癌症疼痛会增加，并且随着疾病的进展往往变得更加难以完全控制。为了深入了解这个问题，我们使用骨癌疼痛的小鼠模型来证明，随着肿瘤在骨内生长，表达原肌球蛋白受体激酶A（TrkA）的感觉和交感神经纤维经历大量发芽并形成神经瘤样结构。为了解决是什么驱动病理性神经重组，我们给予神经生长因子抗体（抗NGF）。早期持续施用抗NGF（其同源受体是TrkA）阻断感觉和交感神经纤维的病理性发芽、神经瘤样结构的形成，并抑制癌痛的发展。这些结果表明，癌细胞及其相关的基质细胞释放NGF，其诱导感觉和交感神经纤维的病理性重塑。这种周围神经系统的病理性重塑参与了癌症疼痛的驱动。与针对癌症本身的疗法类似，本文提供的数据表明，越早开始阻断这种病理性神经重塑的疗法，对癌症疼痛的控制就越有效。
For many patients, pain is the first sign of cancer and, while pain can be present at any time, the frequency and intensity of pain tend to increase with advancing stages of the disease. Thus, between 75 and 90% of patients with metastatic or advanced-stage cancer will experience significant cancer-induced pain. One major unanswered question is why cancer pain increases and frequently becomes more difficult to fully control with disease progression. To gain insight into this question we used a mouse model of bone cancer pain to demonstrate that as tumor growth progresses within bone, Tropomyosin receptor kinase A (TrkA)-expressing sensory and sympathetic nerve fibers undergo profuse sprouting and form neuroma-like structures. To address what is driving the pathological nerve reorganization we administered an antibody to nerve growth factor (anti-NGF). Early sustained administration of anti-NGF, whose cognate receptor is TrkA, blocks the pathological sprouting of sensory and sympathetic nerve fibers, the formation of neuroma-like structures, and inhibits the development of cancer pain. These results suggest that cancer cells and their associated stromal cells release NGF, which induces a pathological remodeling of sensory and sympathetic nerve fibers. This pathological remodeling of the peripheral nervous system then participates in driving cancer pain. Similar to therapies that target the cancer itself, the data presented here suggest that the earlier that therapies blocking this pathological nerve remodeling are initiated, the more effective the control of cancer pain.
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影响因子：
7.4
作者：
Jimenez-Andrade, Juan M.;Martin, Carl D.;Mantyh, Patrick W.
通讯作者：
Mantyh, Patrick W.
影响因子：
29.4
作者：
Ceyhan, Gueralp O.;Bergmann, Frank;Friess, Helmut
通讯作者：
Friess, Helmut
影响因子：
1.9
作者：
Inman, VT;Saunders, JBDM
通讯作者：
Saunders, JBDM
影响因子：
5.5
作者：
LAWSON, SN;WADDELL, PJ
通讯作者：
WADDELL, PJ
影响因子：
11.2
作者：
Halvorson, KG;Kubota, K;Mantyh, PW
通讯作者：
Mantyh, PW