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学科主题: 基础医学
题名:
Enhanced excitability of small dorsal root ganglion neurons in rats with bone cancer pain
作者: 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
发表日期: 2012-04-03
DOI: 10.1186/1744-8069-8-24
卷: 8, 期:1
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Neurosciences
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
项目资助者: 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)
WOS记录号: WOS:000305478500001
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61657
Appears in Collections:基础医学院_神经生物学系_期刊论文

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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

Recommended Citation:
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).
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