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NADPH oxidase 2-derived reactive oxygen species in spinal cord microglia contribute to peripheral nerve injury-induced neuropathic pain.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Kim, Donghoon You, Byunghyun Jo, Eun-Kyeong Han, Sang-Kyou Simon, Melvin I. Lee, Sung Joong |
| Copyright Year | 2010 |
| Abstract | Increasing evidence supports the notion that spinal cord microglia activation plays a causal role in the development of neuropathic pain after peripheral nerve injury; yet the mechanisms for microglia activation remain elusive. Here, we provide evidence that NADPH oxidase 2 (Nox2)-derived ROS production plays a critical role in nerve injury-induced spinal cord microglia activation and subsequent pain hypersensitivity. Nox2 expression was induced in dorsal horn microglia immediately after L5 spinal nerve transection (SNT). Studies using Nox2-deficient mice show that Nox2 is required for SNT-induced ROS generation, microglia activation, and proinflammatory cytokine expression in the spinal cord. SNT-induced mechanical allodynia and thermal hyperalgesia were similarly attenuated in Nox2-deficient mice. In addition, reducing microglial ROS level via intrathecal sulforaphane administration attenuated mechanical allodynia and thermal hyperalgesia in SNT-injured mice. Sulforaphane also inhibited SNT-induced proinflammatory gene expression in microglia, and studies using primary microglia indicate that ROS generation is required for proinflammatory gene expression in microglia. These studies delineate a pathway involving nerve damage leading to microglial Nox2-generated ROS, resulting in the expression of proinflammatory cytokines that are involved in the initiation of neuropathic pain. |
| File Format | PDF HTM / HTML |
| DOI | 10.1073/pnas.1009926107 |
| PubMed reference number | 20679217 |
| Journal | Medline |
| Volume Number | 107 |
| Issue Number | 33 |
| Alternate Webpage(s) | http://www.pnas.org/content/107/33/14851.full.pdf |
| Alternate Webpage(s) | https://doi.org/10.1073/pnas.1009926107 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
