mir-500-Mediated GAD67 Downregulation Contributes to Neuropathic Pain.
Neuropathic pain is a common neurobiological disease involving multifaceted maladaptations ranging from gene modulation to synaptic dysfunction, but the interactions between synaptic dysfunction and the genes that are involved in persistent pain remain elusive. In the present study, we found that neuropathic pain induced by the chemotherapeutic drug paclitaxel or L5 ventral root transection significantly impaired the function of GABAergic synapses of spinal dorsal horn neurons via the reduction of the GAD67 expression. We also found that mir-500 expression was significantly increased and involved in the modulation of GAD67 expression via targeting the specific site of Gad1 gene in the dorsal horn. In addition, knock-out of mir-500 or using mir-500 antagomir rescued the GABAergic synapses in the spinal dorsal horn neurons and attenuated the sensitized pain behavior in the rats with neuropathic pain. To our knowledge, this is the first study to investigate the function significance and the underlying molecular mechanisms of mir-500 in the process of neuropathic pain, which sheds light on the development of novel therapeutic options for neuropathic pain.



Neuropathic pain is a common neurobiological disease involving multifaceted maladaptations ranging from gene modulation to synaptic dysfunction, but the underlying molecular mechanisms remain elusive. The present study illustrates for the first time a mir-500-mediated mechanism underlying spinal GABAergic dysfunction and sensitized pain behavior in neuropathic pain induced by the chemotherapeutic drug paclitaxel or L5 ventral root transection, which sheds light on the development of novel therapeutic options for neuropathic pain.
Zhongshan Medical School, Guangdong Province Key Laboratory of Brain Function and Disease, Sun Yat-Sen University, Guangzhou 510080, China.
Zhen-Zhen
ZZ
Huang
Zhongshan Medical School, Guangdong Province Key Laboratory of Brain Function and Disease, Sun Yat-Sen University, Guangzhou 510080, China.
Jia-You
JY
Wei
Department of Anesthesiology, State Key Laboratory of Oncology in Southern China, Sun Yat-Sen Universtiy Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China, and.
Han-Dong
0000-0003-3992-9653
HD
Ou-Yang
Zhongshan Medical School, Guangdong Province Key Laboratory of Brain Function and Disease, Sun Yat-Sen University, Guangzhou 510080, China.
Dai
D
Li
Zhongshan Medical School, Guangdong Province Key Laboratory of Brain Function and Disease, Sun Yat-Sen University, Guangzhou 510080, China.
Ting
T
Xu
Department of Rehabilitation Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
Shao-Ling
SL
Wu
Zhongshan Medical School, Guangdong Province Key Laboratory of Brain Function and Disease, Sun Yat-Sen University, Guangzhou 510080, China.
Xiao-Long
XL
Zhang
Department of Rehabilitation Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
Cui-Cui
CC
Liu
Department of Rehabilitation Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
Chao
C
Ma
Zhongshan Medical School, Guangdong Province Key Laboratory of Brain Function and Disease, Sun Yat-Sen University, Guangzhou 510080, China, xinwj@mail.sysu.edu.cn.
Wen-Jun
0000-0002-5380-8738
WJ
Xin
D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000818:Animals; D000070416:Antagomirs / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics*; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism*; D006930:Hyperalgesia; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009437:Neuralgia / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D000069896:Transcription Activator-Like Effector Nucleases / Q000235:genetics / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000070416:Antagomirs; D000972:Antineoplastic Agents, Phytogenic; D035683:MicroRNAs; D005680:gamma-Aminobutyric Acid; D000069896:Transcription Activator-Like Effector Nucleases; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D017239:Paclitaxel
GAD67; L5 ventral root transection; mir-500; neuropathic pain; paclitaxel