Interleukin-2 gene therapy of chronic neuropathic pain

	Interleukin-2 gene therapy of chronic neuropathic pain
	Yao, MZ; Gu, JF; Wang, JH; Sun, LY; Lang, MF; Liu, J; Zhao, ZQ; Liu, XY
刊名	NEUROSCIENCE
	2002
卷号	112 期号:2 页码:409-416
关键词	interleukin-2 gene transfer intrathecal injection chronic constriction injury antinociceptive effect
通讯作者	Liu, XY (reprint author), Chinese Acad Sci, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,
英文摘要	Previous research has revealed an antinociceptive (analgesic) effect of interleukin-2 (IL-2) in central and peripheral nervous systems. Unfortunately IL-2 is very short-lived in vivo, so it is impractical to apply IL-2 for analgesia in clinic. This study was performed to evaluate the effect of intrathecal delivery of human IL-2 gene on rat chronic neuropathic pain induced by chronic constriction injury of the sciatic nerve. Human IL-2 cDNA was cloned into pcDNA3 containing a cytomegalovirus promoter. The paw-withdrawal latency induced by radiant heat was used to measure the pain threshold. The results showed that recombinant human IL-2 had a dose-dependent antinociceptive effect, but that this only lasted for 10-25 min. The pcDNA3-IL-2 or pcIDNAML-2/ lipofectamine complex in contrast also showed dose-dependent antinociceptive effects, but these reached a peak at day 2-3 and were maintained for up to 6 days. Liposome-mediated pcDNA3-IL-2 produced a more powerful antinociceptive effect than pcDNA3-IL-2 alone. The paw-withdrawal latencies were not affected by control treatments such as vehicle, lipofectamine, pcDNA3, or pcDNA3-lipofectamine. In the experimental groups, human IL-2 mRNA was detected by reverse transcription-polymerase chain reaction in the lumbar spinal pia mater, dorsal root ganglion, sciatic nerve, and spinal dorsal horn, but not in gastrocnemius muscle. The expressed IL-2 profile detected by western blot coincided with its mRNA profile except it was present in the spinal dorsal horn at a higher level. Furthermore, human IL-2 assayed by enzyme-linked immunosorbent assay in cerebrospinal fluid could still be detected at day 6, but lower than day 3. The antinociceptive effect of pcDNA3-IL-2 could be blocked by naloxone, showing some relationship of the antinociceptive effect produced by IL-2 gene to the opioid receptors. It is hoped that the now delivery approach of a single intrathecal injection of the IL-2 gene described here may be of some practical use as a part of a gene therapy for treating neuropathic pain. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.
学科主题	Neurosciences & Neurology
类目[WOS]	Neurosciences
关键词[WOS]	SPINAL SUBARACHNOID SPACE ; CENTRAL-NERVOUS-SYSTEM ; RAT ; IL-2 ; EXPRESSION ; RECEPTOR ; IMMUNOREACTIVITY ; ANTINOCICEPTION ; DELIVERY ; PEPTIDES
收录类别	SCI
语种	英语
WOS记录号	WOS:000176525700016
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/2454]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Yao, MZ,Gu, JF,Wang, JH,et al. Interleukin-2 gene therapy of chronic neuropathic pain[J]. NEUROSCIENCE,2002,112(2):409-416.
APA	Yao, MZ.,Gu, JF.,Wang, JH.,Sun, LY.,Lang, MF.,...&Liu, XY.(2002).Interleukin-2 gene therapy of chronic neuropathic pain.NEUROSCIENCE,112(2),409-416.
MLA	Yao, MZ,et al."Interleukin-2 gene therapy of chronic neuropathic pain".NEUROSCIENCE 112.2(2002):409-416.