Microvesicles shed from microglia activated by the P2X7-p38 pathway are involved in neuropathic pain induced by spinal nerve ligation in rats.
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.
Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China.
Jian
J
Li
Department of Anesthesiology, The Third People's Hospital of Yancheng, Yancheng, 224001, China.
Xiangnan
X
Li
Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China.
Xin
X
Jiang
Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China.
Mei
M
Yang
Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China.
Rui
R
Yang
Autonomic Neuroscience Centre, University College Medical School, London, UK.|Department of Pharmacology and Therapeutics, The University of Melbourne, Melbourne, Australia.
Geoffrey
G
Burnstock
Department of Neurobiology, MOE Key Laboratory of Molecular Neurobiology, Ministry of Education, Second Military Medical University, Shanghai, 200433, China. xiang-zhenghua@163.com.
Zhenghua
0000-0001-7891-5305
Z
Xiang
Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China. jfjczyy@aliyun.com.
Hongbin
H
Yuan
D000818:Animals; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D004195:Disease Models, Animal; D020935:MAP Kinase Signaling System / Q000502:physiology*; D017628:Microglia / Q000378:metabolism*; D009437:Neuralgia / Q000209:etiology / Q000378:metabolism*; D059348:Peripheral Nerve Injuries / Q000150:complications / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism; D013127:Spinal Nerves / Q000293:injuries*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D058486:Receptors, Purinergic P2X7; D048051:p38 Mitogen-Activated Protein Kinases
Microglia; Microvesicles; Neuropathic pain; Spinal nerve ligation, P2X7
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