Tumor suppressor menin mediates peripheral nerve injury-induced neuropathic pain through potentiating synaptic plasticity

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• 作者：S. Xu ; H. Wu ; X. Wang ; X. Shen ; X. Guo ; R. Shen ; F. Wang
• 关键词：ANOVA ; analysis of variance ; ASO ; antisense oligonucleotide ; AUC ; area under curve ; CNS ; central nervous system ; CSF ; cerebrospinal fluid ; EGTA ; ethylene glycol tetraacetic acid ; EPSC ; excitatory postsynaptic current ; fEPSP ; field excitatory postsynaptic
• 刊名：Neuroscience
• 出版年：2012
• 出版时间：25 October, 2012
• 年：2012
• 卷：223
• 期：Complete
• 页码：473-485
• 全文大小：1340 K

文摘

Synaptic plasticity is a crucial step in the development of central sensitization in the pathogenesis of neuropathic hyperalgesia. Menin, the product of the multiple endocrine neoplasia type 1 (MEN1) gene, possesses the property of synaptogenesis which plays an essential role in neuronal activity. We tested the contributing role of spinal menin in peripheral nerve injury-induced neuropathic hypersensitivity through modulating neuronal synaptic plasticity. After approval by the Institutional Animal Care and Use Committee, nociceptive responses were detected with von Frey filaments and thermal plate after spared nerve injury in C57BL/6 mice who were treated with either intrathecal antisense oligonucleotide of MEN1 (ASO) or vehicle. Extracellular spontaneous discharge frequency, field excitatory postsynaptic potential (fEPSP), and monosynaptic excitatory postsynaptic currents (EPSCs) were measured electrophysiologically. Intrathecal ASO alleviated nerve injury-induced mechanical and thermal hypersensitivity. Upregulated spinal menin after nerve injury colocalized with NeuN in the superficial laminae; genetic knockdown of spinal menin reduced nerve injury induced in vivo spontaneous activity and instantaneous frequency and in vitro field potentials; ASO decreased the frequency and amplitude of monosynaptic EPSCs, and reduced synaptic strength and total charge. Collectively, these findings highlight the role of upregulated neuronal menin in the spinal cord in potentiating spinal synaptic plasticity in peripheral nerve injury-induced neuropathic hypersensitivity.