期刊
JOURNAL OF NEUROSCIENCE
卷 36, 期 23, 页码 6321-6331出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0646-16.2016
关键词
GAD67; L5 ventral root transection; mir-500; neuropathic pain; paclitaxel
资金
- National Natural Science Foundation of China [81271474, 81300966, 81171469]
- Fundamental Research Funds for the Central Universities [15ykjco4b]
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.
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