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癌症疼痛小鼠模型中伤害性背根神经节神经元反应特性的变化。

Changes in response properties of nociceptive dorsal horn neurons in a murine model of cancer pain.

作者信息

Simone Donald A, Khasabov Sergey G, Hamamoto Darryl T

机构信息

Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, Minnesota 55455, USA.

出版信息

Sheng Li Xue Bao. 2008 Oct 25;60(5):635-44.

PMID:18958372
Abstract

Pain associated with cancer that metastasizes to bone is often severe and debilitating. A better understanding of the neural mechanisms that mediate cancer pain is needed for the development of more effective treatments. In this study, we used an established model of cancer pain to characterize changes in response properties of dorsal horn neurons. Fibrosarcoma cells were implanted into and around the calcaneus bone in mice and extracellular electrophysiological recordings were made from wide dynamic range (WDR) and high threshold (HT) dorsal horn neurons. Responses of WDR and HT neurons evoked by mechanical, heat, and cold stimuli applied to the plantar surface of the hind paw were compared between tumor bearing mice and control mice. Mice exhibited hyperalgesia to mechanical and heat stimuli applied to their tumor-bearing hind paw. WDR neurons in tumor-bearing mice exhibited an increase in spontaneous activity, and enhanced responses to mechanical, heat, and cold stimuli as compared to controls. Our findings show that sensitization of WDR neurons, but not HT neurons, contributes to tumor-evoked hyperalgesia.

摘要

转移至骨骼的癌症相关疼痛通常很严重且使人衰弱。为了开发更有效的治疗方法,需要更好地理解介导癌症疼痛的神经机制。在本研究中,我们使用一种已确立的癌症疼痛模型来表征背角神经元反应特性的变化。将纤维肉瘤细胞植入小鼠跟骨及其周围,然后从宽动态范围(WDR)和高阈值(HT)背角神经元进行细胞外电生理记录。比较了荷瘤小鼠和对照小鼠中,后爪足底受到机械、热和冷刺激时WDR和HT神经元的反应。小鼠对施加于其荷瘤后爪的机械和热刺激表现出痛觉过敏。与对照组相比,荷瘤小鼠中的WDR神经元自发活动增加,并且对机械、热和冷刺激的反应增强。我们的研究结果表明,WDR神经元而非HT神经元的敏化导致肿瘤诱发的痛觉过敏。

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