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HSV-mediated expression of interleukin-4 in dorsal root ganglion neurons reduces neuropathic pain
被引:109
作者:
Hao, Shuanglin
Mata, Marina
Glorioso, Joseph C.
Fink, David J.
机构:
[1] Univ Michigan Hlth Syst, Dept Neurol, Ann Arbor, MI 48109 USA
[2] Univ Pittsburgh, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA
[3] VA Ann Arbor Healthcare Syst, Ann Arbor, MI 48105 USA
来源:
关键词:
D O I:
10.1186/1744-8069-2-6
中图分类号:
Q189 [神经科学];
学科分类号:
071006 ;
摘要:
Background: To examine the role of inflammatory mediators in neuropathic pain, we used a replication-defective genomic herpes simplex virus (HSV)-based vector containing the coding sequence for the anti-inflammatory peptide interleukin (IL)-4 under the transcriptional control of the HSV ICP4 immediate early promoter, vector S4IL4, to express IL-4 in dorsal root ganglion (DRG) neurons in vivo. Results: Subcutaneous inoculation of S4IL4 in the foot transduced lumbar DRG to produce IL-4. Transgene-mediated expression of IL-4 did not alter thermal latency or tactile threshold in normal animals, but inoculation of S4IL4 1 week after spinal nerve ligation (SNL) reduced mechanical allodynia and reversed thermal hyperalgesia resulting from SNL. Inoculation of S4IL4 1 week before SNL delayed the development of thermal hyperalgesia and tactile allodynia, but did not prevent the ultimate development of these manifestations of neuropathic pain. S4IL4 inoculation suppressed non-noxious-induced expression of c-Fos immunoreactivity in dorsal horn of spinal cord and reversed the upregulation of spinal IL-I beta, PGE2, and phosphorylated-p38 MAP kinase, characteristic of neuropathic pain. Conclusion: HSV-mediated expression of IL-4 effectively reduces the behavioral manifestations of neuropathic pain, and reverses some of the biochemical and histologic correlates of neuropathic pain at the spinal level.
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页数:9
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