Hedgehog signaling contributes to bone cancer pain by regulating sensory neuron excitability in rats.
Hedgehog signaling contributes to bone cancer pain by regulating sensory neuron excitability in rats.
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Hedgehog 信号通过调节大鼠感觉神经元兴奋性导致骨癌疼痛
DOI：
10.1177/1744806918767560
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发表时间：
2018-01
期刊：
影响因子：
3.3
通讯作者：
Liu GJ
中科院分区：
文献类型：
--
作者：
Liu S;Lv Y;Wan XX;Song ZJ;Liu YP;Miao S;Wang GL;Liu GJ
治疗骨癌疼痛仍然是一个临床挑战，骨癌疼痛的潜在机制仍然难以捉摸。在这里，我们报道了音刺猬信号在骨癌疼痛的发展中起着至关重要的作用。胫骨骨腔肿瘤细胞植入可产生骨癌相关的机械性异常性疼痛、热痛觉过敏以及自发性和运动诱发性疼痛行为。这些疼痛行为的产生和持续与肿瘤细胞增殖诱导的初级感觉神经元和脊髓中的音刺猬信号的上调和激活密切相关。脊髓给药音刺猬信号抑制剂环巴胺预防和逆转骨癌疼痛的诱导和持续，而不影响正常的疼痛敏感性。在体内或体外用环巴胺抑制音刺猬信号激活，极大地抑制了肿瘤细胞增殖诱导的细胞内Ca 2+的增加和感觉神经元的过度兴奋，以及背根神经节和脊髓中GluN2B受体的激活和随后的Ca 2+依赖性信号CaMK II和CREB。这些发现显示了骨癌疼痛发病机制的关键机制，并表明靶向音刺猬信号可能是治疗骨癌疼痛的有效方法。
Treating bone cancer pain continues to be a clinical challenge and underlying mechanisms of bone cancer pain remain elusive. Here, we reported that sonic hedgehog signaling plays a critical role in the development of bone cancer pain. Tibia bone cavity tumor cell implantation produces bone cancer-related mechanical allodynia, thermal hyperalgesia, and spontaneous and movement-evoked pain behaviors. Production and persistence of these pain behaviors are well correlated with tumor cell implantation-induced up-regulation and activation of sonic hedgehog signaling in primary sensory neurons and spinal cord. Spinal administration of sonic hedgehog signaling inhibitor cyclopamine prevents and reverses the induction and persistence of bone cancer pain without affecting normal pain sensitivity. Inhibiting sonic hedgehog signaling activation with cyclopamine, in vivo or in vitro, greatly suppresses tumor cell implantation-induced increase of intracellular Ca2+ and hyperexcitability of the sensory neurons and also the activation of GluN2B receptor and the subsequent Ca2+-dependent signals CaMKII and CREB in dorsal root ganglion and the spinal cord. These findings show a critical mechanism underlying the pathogenesis of bone cancer pain and suggest that targeting sonic hedgehog signaling may be an effective approach for treating bone cancer pain.
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胰腺星状细胞通过激活 sHH 信号通路导致胰腺癌疼痛
影响因子：
--
作者：
Han L;Ma J;Duan W;Zhang L;Yu S;Xu Q;Lei J;Li X;Wang Z;Wu Z;Huang JH;Wu E;Ma Q;Ma Z
通讯作者：
Ma Z
DOI：
10.1073/pnas.191352298
发表时间：
2001-09-25
影响因子：
11.1
作者：
West, AE;Chen, WG;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
4
作者：
Mitchell, Nicholas;Petralia, Ronald S.;Yao, Pamela J.
通讯作者：
Yao, Pamela J.
脑源性神经营养因子调节癌症引起的骨痛大鼠模型中 N-甲基-D-天冬氨酸受体的激活
影响因子：
4.2
作者：
Wang, Li-Na;Yang, Jian-Ping;Zuo, Jian-Ling
通讯作者：
Zuo, Jian-Ling
影响因子：
9.2
作者：
Babcock, Daniel T.;Shi, Shanping;Jo, Juyeon;Shaw, Michael;Gutstein, Howard B.;Galko, Michael J.
通讯作者：
Galko, Michael J.