期刊
JOURNAL OF NEUROINFLAMMATION
卷 12, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/s12974-015-0280-1
关键词
Chronic constriction injury; Intrathecal; Astrocyte; Neuroinflammation
资金
- Ministry of Science and Technology, Taiwan [102-2325-B-110-002, 101-2314-B-182A-023-MY2, 103-2325-B-110 -001, 103-2314-B-075 -031]
- Taipei Veterans General Hospital, Taiwan [V102C-198]
- projects of Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan [KMU-TP103G00, KMU-TP103G02-05]
Background: Many cancer research studies have extensively examined the phosphatase and tensin homolog deleted from chromosome 10 (PTEN) pathway. There are only few reports that suggest that PTEN might affect pain; however, there is still a lack of evidence to show the role of PTEN for modulating pain. Here, we report a role for PTEN in a rodent model of neuropathic pain. Results: We found that chronic constriction injury (CCI) surgery in rats could elicit downregulation of spinal PTEN as well as upregulation of phosphorylated PTEN (phospho-PTEN) and phosphorylated mammalian target of rapamycin (phospho-mTOR). After examining such changes in endogenous PTEN in neuropathic rats, we explored the effects of modulating the spinal PTEN pathway on nociceptive behaviors. The normal rats exhibited mechanical allodynia after intrathecal (i.t.) injection of adenovirus-mediated PTEN antisense oligonucleotide (Ad-antisense PTEN). These data indicate the importance of downregulation of spinal PTEN for nociception. Moreover, upregulation of spinal PTEN by i.t. adenovirus-mediated PTEN (Ad-PTEN) significantly prevented CCI-induced development of nociceptive sensitization, thermal hyperalgesia, mechanical allodynia, cold allodynia, and weight-bearing deficits in neuropathic rats. Furthermore, upregulation of spinal PTEN by i.t. Ad-PTEN significantly attenuated CCI-induced microglia and astrocyte activation, upregulation of tumor necrosis factor-alpha (TNF-alpha) and phospho-mTOR, and downregulation of PTEN in neuropathic rats 14 days post injury. Conclusions: These findings demonstrate that PTEN plays a key, beneficial role in a rodent model of neuropathic pain.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据