title: Rapamycin ameliorates neuropathic pain by activating autophagy and inhibiting interleukin-1β in the rat spinal cord.
abstract: Autophagy acts as an important homoeostatic mechanism by degradation of cytosolic constituents 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 of neuropathic 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 spinal microglia and increased mRNA 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.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.|Department of Anesthesiology, Xixiang people's Hospital of Bao'an District, Shenzhen, 518100, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Feng
authors.affiliation: 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.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yin
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Ze-Lin
authors.initials: ZL
authors.lastname: Weng
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Jian-Cheng
authors.initials: JC
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Xixiang people's Hospital of Bao'an District, Shenzhen, 518100, China.
authors.forename: Kun-Feng
authors.initials: KF
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. yuanshiying@yahoo.com.
authors.forename: Shi-Ying
authors.initials: SY
authors.lastname: Yuan
authors.affiliation: 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. cheng.wei.1@hotmail.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D007166:Immunosuppressive Agents; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020123:Sirolimus / Q000494:pharmacology*; D013131:Spine / Q000378:metabolism* / Q000473:pathology
chemical_list: C000594089:IL1B protein, rat; D007166:Immunosuppressive Agents; D053583:Interleukin-1beta; D012333:RNA, Messenger; D020123:Sirolimus