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Dynamic long-term microstructural and ultrastructural alterations in sensory nerves of rats of paclitaxel-induced neuropathic pain
Wu Yuan; Li Jun; Zhou Junfei; Feng Yi
关键词paclitaxel neuropathic pain ultrastructure microstructure
刊名CHINESE MEDICAL JOURNAL
2014-08-20
DOI10.3760/cma.j.issn.0366-6999.20140727
127期:16页:2945-2952
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Medicine, General & Internal
研究领域[WOS]General & Internal Medicine
关键词[WOS]ACETYL-L-CARNITINE ; PERIPHERAL NEUROPATHY ; ANIMAL-MODELS ; MECHANISMS ; NEURONS ; FIBER ; SENSITIZATION ; DEMYELINATION ; GANGLIA ; HUMANS
英文摘要

Background Paclitaxel, as a first line anti-neoplastic compound, frequently produces long-term pain after tumors have been treated. Clinical manifestations are varied and non-specific. Pathology of the nervous system during the development of the neuropathic pain is unclear. Thus, early diagnosis and treatment is often unsatisfying for patients. This study aimed to promote considerate understanding of the structural alteration of sensory nerves.

Methods All rats were simply randomized into 3 groups: paclitaxel group, vehicle group and saline group. An established rat model of paclitaxel-induced peripheral neuropathy (2 mg/kg) was chosen for our research, behavior tests were operated during the procedure of 56 days. All rats were sampled on days 0, 3, 7, 28 and 56. The hind paw plantar skin, sciatic nerves, dorsal root ganglion and attached fibers, and lumbar spinal cord were processed for light and electron microscopy. The differences among 3 groups were analyzed with one-way analysis of variance (ANOVA).

Results We affirmed that paclitaxel-induced mechano-allodynia and mechano-hyperalgesia occured after a 3-7-day delay, and this pain peaked at day 28 and persisted to day 56. Paclitaxel and vehicle treatment both evoked thermal-hyperalgesia. Paclitaxel-induced axonal and myelin sheath degeneration was evident. At days 3 and 7, significant increases in atypical mitochondria in both myelinated axons and C-fibers of paclitaxel-treated nerves indicated that injured mitochondria correlated to specific paclitaxel-induced neuropathic pain, and the abnorrnity sustained till day 56. Microtubule was unaffected in myelinated axons or C-fibers in paclitaxel- or vehicle-treated rats. Significant increase of G ratio was evident with paclitaxel injection at days 7 and 28.

Conclusion Our research suggests a causal role for axonal degeneration, abnormalities in axonal mitochondria, and structural modification of axonal microtubules in paclitaxel-induced neuropathic pain, and the abnormal mitochondria could be connected to the chronic neuropathic pain.

语种英语
WOS记录号WOS:000347491900013
项目编号7112138
资助机构Beijing Natural Science Foundation
引用统计
被引频次:2[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/59111
专题北京大学第二临床医学院
北京大学第二临床医学院_麻醉科
作者单位Peking Univ, Peoples Hosp, Dept Anesthesia, Beijing 100044, Peoples R China
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GB/T 7714
Wu Yuan,Li Jun,Zhou Junfei,et al. Dynamic long-term microstructural and ultrastructural alterations in sensory nerves of rats of paclitaxel-induced neuropathic pain[J]. CHINESE MEDICAL JOURNAL,2014,127(16):2945-2952.
APA Wu Yuan,Li Jun,Zhou Junfei,&Feng Yi.(2014).Dynamic long-term microstructural and ultrastructural alterations in sensory nerves of rats of paclitaxel-induced neuropathic pain.CHINESE MEDICAL JOURNAL,127(16),2945-2952.
MLA Wu Yuan,et al."Dynamic long-term microstructural and ultrastructural alterations in sensory nerves of rats of paclitaxel-induced neuropathic pain".CHINESE MEDICAL JOURNAL 127.16(2014):2945-2952.
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