Rapamycin Ameliorates Neuropathic Pain by Activating Autophagy and Inhibiting Interleukin-1β in the Rat Spinal Cord
Autophagy acts as an important homoeostatic mechanism by degradation of cytosolic con- stituents and plays roles in many physiological processes. Recent studies demonstrated that autophagy can also regulate the production and secretion of the proinflammatory cytokine interleukin-1β （IL-1β）, which pl...
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| Summary: | Autophagy acts as an important homoeostatic mechanism by degradation of cytosolic con- stituents and plays roles in many physiological processes. Recent studies demonstrated that autophagy can also regulate the production and secretion of the proinflammatory cytokine interleukin-1β （IL-1β）, which plays a critical role in the development and maintenance ofneuropathic pain. In the present study, the paw withdrawal threshold （PWT） and paw withdrawal latency （PWL） were significantly decreased after spinal nerve ligation （SNL）, and the changes were accompanied by inhibited autophagy in the spi- nal microglia and increased mR.NA and protein levels of IL-1β in the ipsilateral spinal cord. We then investigated the antinociceptive effect of rapamycin, a widely used autopahgy inducer, on SNL-induced neuropathic pain in rats and found that treatment with intrathecal rapamycin significantly attenuated the mechanical allodynia and thermal hyperalgesia. Moreover, rapamycin significantly enhanced autophagy in the spinal microglia, whereas it reduced the mRNA and protein levels of IL-1β in the ipsilateral spinal cord. Our results showed that rapamycin could ameliorate neuropathic pain by activating autophagy and inhibiting IL-1β in the spinal cord. |
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| Bibliography: | 42-1679/R Autophagy acts as an important homoeostatic mechanism by degradation of cytosolic con- stituents and plays roles in many physiological processes. Recent studies demonstrated that autophagy can also regulate the production and secretion of the proinflammatory cytokine interleukin-1β （IL-1β）, which plays a critical role in the development and maintenance ofneuropathic pain. In the present study, the paw withdrawal threshold （PWT） and paw withdrawal latency （PWL） were significantly decreased after spinal nerve ligation （SNL）, and the changes were accompanied by inhibited autophagy in the spi- nal microglia and increased mR.NA and protein levels of IL-1β in the ipsilateral spinal cord. We then investigated the antinociceptive effect of rapamycin, a widely used autopahgy inducer, on SNL-induced neuropathic pain in rats and found that treatment with intrathecal rapamycin significantly attenuated the mechanical allodynia and thermal hyperalgesia. Moreover, rapamycin significantly enhanced autophagy in the spinal microglia, whereas it reduced the mRNA and protein levels of IL-1β in the ipsilateral spinal cord. Our results showed that rapamycin could ameliorate neuropathic pain by activating autophagy and inhibiting IL-1β in the spinal cord. Tao FENG , Qin YIN , Ze-lin WENG , Jian-cheng ZHANG , Kun-feng WANG , Shi-ying YUAN , Wei CHENG （ 1 Department of Anes-thesiology and Intensive Care Medicine, Union Hospital Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; 2 Department of Anesthesiology, Xixiang people ＇s Hospital of Bao ＇an District, Shenzhen 518100, China; 3 Jiangsu Province Key, Laboratory of Anesthesiology and Center for Pain Research and Treatment, Jiangsu Province Key Laboratory of Anesthesiology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China） rapamycin, autophagy, interleukin- 1β, neuropathic pain ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 1672-0733 1993-1352 |
| DOI: | 10.1007/s11596-014-1361-6 |