Microvesicles shed from microglia activated by the P2X7-p38 pathway are involved in neuropathic pain induced by spinal nerve ligation in rats |
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| Authors: | Jian Li Xiangnan Li Xin Jiang Mei Yang Rui Yang Geoffrey Burnstock Zhenghua Xiang Hongbin Yuan |
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| Institution: | 1.Department of Anesthesiology, Changzheng Hospital,Second Military Medical University,Shanghai,China;2.Department of Anesthesiology,The Third People’s Hospital of Yancheng,Yancheng,China;3.Autonomic Neuroscience Centre,University College Medical School,London,UK;4.Department of Pharmacology and Therapeutics,The University of Melbourne,Melbourne,Australia;5.Department of Neurobiology, MOE Key Laboratory of Molecular Neurobiology, Ministry of Education,Second Military Medical University,Shanghai,China |
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| Abstract: | Microglia are critical in the pathogenesis of neuropathic pain. In this study, we investigated the role of microvesicles (MVs) in neuropathic pain induced by spinal nerve ligation (SNL) in rats. First, we found that MVs shed from microglia were increased in the cerebrospinal fluid and dorsal horn of the spinal cord after SNL. Next, MVs significantly reduced paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). In addition, the P2X7-p38 pathway was related to the bleb of MVs after SNL. Interleukin (IL)-1β was found to be significantly upregulated in the package of MVs, and PWT and PWL increased following inhibition with shRNA-IL-1β. Finally, the amplitude and frequency of spontaneous excitatory postsynaptic currents increased following stimulation with MVs. Our results indicate that the P2X7-p38 pathway is closely correlated with the shedding of MVs from microglia in neuropathic pain, and MVs had a significant effect on neuropathic pain by participating in the interaction between microglia and neurons. |
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