IR@PKUHSC  > 北京大学基础医学院  > 神经生物学系
学科主题基础医学
Enhanced excitability of small dorsal root ganglion neurons in rats with bone cancer pain
Zheng, Qin1,2,3,4; Fang, Dong1,2,3,4; Cai, Jie1,2,3,4; Wan, You1,2,3,4; Han, Ji-Sheng1,2,3,4; Xing, Guo-Gang1,2,3,4
关键词Bone cancer pain Hyperalgesia hyperexcitability Peripheral sensitization Dorsal root ganglion rat
刊名MOLECULAR PAIN
2012-04-03
DOI10.1186/1744-8069-8-24
8期:1
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Neurosciences
资助者National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Foundation of the Ministry of Education for Returned Scholars ; National Basic Research Program of China (973 Program) ; National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Foundation of the Ministry of Education for Returned Scholars ; National Basic Research Program of China (973 Program)
研究领域[WOS]Neurosciences & Neurology
关键词[WOS]PRIMARY AFFERENT NEURONS ; SPINAL NERVE LIGATION ; NR2B-CONTAINING NMDA RECEPTORS ; TUMOR-EVOKED HYPERALGESIA ; C-FIBER NOCICEPTORS ; NEUROPATHIC PAIN ; PERIPHERAL-NERVE ; MEMBRANE-PROPERTIES ; SENSORY NEURONS ; MURINE MODEL
英文摘要

Background: Primary and metastatic cancers that affect bone are frequently associated with severe and intractable pain. The mechanisms underlying the development of bone cancer pain are largely unknown. The aim of this study was to determine whether enhanced excitability of primary sensory neurons contributed to peripheral sensitization and tumor-induced hyperalgesia during cancer condition. In this study, using techniques of whole-cell patch-clamp recording associated with immunofluorescent staining, single-cell reverse-transcriptase PCR and behavioral test, we investigated whether the intrinsic membrane properties and the excitability of small-sized dorsal root ganglion (DRG) neurons altered in a rat model of bone cancer pain, and whether suppression of DRG neurons activity inhibited the bone cancer-induced pain.

Results: Our present study showed that implantation of MRMT-1 tumor cells into the tibial canal in rats produced significant mechanical and thermal hyperalgesia in the ipsilateral hind paw. Moreover, implantation of tumor cells provoked spontaneous discharges and tonic excitatory discharges evoked by a depolarizing current pulse in small-sized DRG neurons. In line with these findings, alterations in intrinsic membrane properties that reflect the enhanced neuronal excitability were observed in small DRG neurons in bone cancer rats, of which including: 1) depolarized resting membrane potential (RMP); 2) decreased input resistance (R-in); 3) a marked reduction in current threshold (CT) and voltage threshold (TP) of action potential (AP); 4) a dramatic decrease in amplitude, overshot, and duration of evoked action potentials as well as in amplitude and duration of afterhyperpolarization (AHP); and 5) a significant increase in the firing frequency of evoked action potentials. Here, the decreased AP threshold and increased firing frequency of evoked action potentials implicate the occurrence of hyperexcitability in small-sized DRG neurons in bone cancer rats. In addiotion, immunofluorescent staining and single-cell reverse-transcriptase PCR revealed that in isolated small DRG neurons, most neurons were IB4- positive, or expressed TRPV1 or CGRP, indicating that most recorded small DRG neurons were nociceptive neurons. Finally, using in vivo behavioral test, we found that blockade of DRG neurons activity by TTX inhibited the tumor-evoked mechanical allodynia and thermal hyperalgesia in bone cancer rats, implicating that the enhanced excitability of primary sensory neurons underlied the development of bone cancer pain.

Conclusions: Our present results suggest that implantation of tumor cells into the tibial canal in rats induces an enhanced excitability of small-sized DRG neurons that is probably as results of alterations in intrinsic electrogenic properties of these neurons. Therefore, alterations in intrinsic membrane properties associated with the hyperexcitability of primary sensory neurons likely contribute to the peripheral sensitization and tumor-induced hyperalgesia under cancer condition.

语种英语
所属项目编号31171063 ; 81072951 ; 61027001 ; 7112079 ; 2008890 ; 2007CB512501
资助者National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Foundation of the Ministry of Education for Returned Scholars ; National Basic Research Program of China (973 Program) ; National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Foundation of the Ministry of Education for Returned Scholars ; National Basic Research Program of China (973 Program)
WOS记录号WOS:000305478500001
引用统计
被引频次:24[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/61657
专题北京大学基础医学院_神经生物学系
作者单位1.Peking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
2.Peking Univ, Dept Neurobiol, Beijing 100191, Peoples R China
3.Minist Publ Hlth, Beijing 100191, Peoples R China
4.Minist Educ, Key Lab Neurosci, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Zheng, Qin,Fang, Dong,Cai, Jie,et al. Enhanced excitability of small dorsal root ganglion neurons in rats with bone cancer pain[J]. MOLECULAR PAIN,2012,8(1).
APA Zheng, Qin,Fang, Dong,Cai, Jie,Wan, You,Han, Ji-Sheng,&Xing, Guo-Gang.(2012).Enhanced excitability of small dorsal root ganglion neurons in rats with bone cancer pain.MOLECULAR PAIN,8(1).
MLA Zheng, Qin,et al."Enhanced excitability of small dorsal root ganglion neurons in rats with bone cancer pain".MOLECULAR PAIN 8.1(2012).
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