鞘内
神经病理性疼痛
医学
质粒
白细胞介素1β
麻醉
白细胞介素
DNA
药理学
免疫学
生物
遗传学
细胞因子
作者
Erin D. Milligan,Evan M. Sloane,Stephen J. Langer,Travis Hughes,Brian Jekich,Matthew G. Frank,John H. Mahoney,Lindsay H. Levkoff,Steven F. Maier,Pedro Cruz,Terence R. Flotte,Kirk W. Johnson,Melissa M. Mahoney,Raymond A. Chavez,Leslie A. Leinwand,Linda R. Watkins
出处
期刊:Pain
[Ovid Technologies (Wolters Kluwer)]
日期:2006-12-01
卷期号:126 (1): 294-308
被引量:174
标识
DOI:10.1016/j.pain.2006.07.009
摘要
Neuropathic pain is a major clinical problem unresolved by available therapeutics. Spinal cord glia play a pivotal role in neuropathic pain, via the release of proinflammatory cytokines. Anti-inflammatory cytokines, like interleukin-10 (IL-10), suppress proinflammatory cytokines. Thus, IL-10 may provide a means for controlling glial amplification of pain. We recently documented that intrathecal IL-10 protein resolves neuropathic pain, albeit briefly (approximately 2-3 h), given its short half-life. Intrathecal gene therapy using viruses encoding IL-10 can also resolve neuropathic pain, but for only approximately 2 weeks. Here, we report a novel approach that dramatically increases the efficacy of intrathecal IL-10 gene therapy. Repeated intrathecal delivery of plasmid DNA vectors encoding IL-10 (pDNA-IL-10) abolished neuropathic pain for greater than 40 days. Naked pDNA-IL-10 reversed chronic constriction injury (CCI)-induced allodynia both shortly after nerve injury as well as 2 months later. This supports that spinal proinflammatory cytokines are important in both the initiation and maintenance of neuropathic pain. Importantly, pDNA-IL-10 gene therapy reversed mechanical allodynia induced by CCI, returning rats to normal pain responsiveness, without additional analgesia. Together, these data suggest that intrathecal IL-10 gene therapy may provide a novel approach for prolonged clinical pain control.
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