Impaired neuropathic pain and preserved acute pain in rats overexpressing voltage-gated potassium channel subunit Kv1.2 in primary afferent neurons.

Impaired neuropathic pain and preserved acute pain in rats overexpressing voltage-gated potassium channel subunit Kv1.2 in primary afferent neurons.
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DOI:
10.1186/1744-8069-10-8
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发表时间:
2014-01-29
期刊:
影响因子:
3.3
通讯作者:
Tao YX
Tao YX
中科院分区:
医学3区
文献类型:
--
作者:
Fan L;Guan X;Wang W;Zhao JY;Zhang H;Tiwari V;Hoffman PN;Li M;Tao YX

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电压门控钾离子通道在控制神经元兴奋性中起关键作用,并参与神经病理性疼痛的诱导。因此,Kv通道可能是预防和/或治疗这种疾病的潜在靶点。我们在这里报告,大多数背根神经节(DRG)神经元阳性的Kv通道α亚基Kv1.2。大部分都是大的和中等的,虽然有各种各样的大小。腰(L)5脊神经结扎(SNL)引起的周围神经损伤,在同侧L5背根神经节中Kv1.2阳性神经元的数量产生了时间依赖性的减少,但在对侧L5背根神经节中没有。坐骨神经切断后第7天,在同侧L5 DRG中也观察到这种减少。在损伤的L5 DRG中,拯救神经损伤诱导的Kv1.2减少减弱了SNL诱导的疼痛超敏反应的发展和维持,而不影响急性疼痛和运动功能。这种作用可能是由于SNL诱导的内源性Kv1.2反义RNA的上调,除了在Kv1.2蛋白表达的增加,在受损的DRG中的预防。我们的研究结果表明Kv1.2可能是预防和/或治疗神经病理性疼痛的一个新的潜在靶点。
Voltage-gated potassium (Kv) channels are critical in controlling neuronal excitability and are involved in the induction of neuropathic pain. Therefore, Kv channels might be potential targets for prevention and/or treatment of this disorder. We reported here that a majority of dorsal root ganglion (DRG) neurons were positive for Kv channel alpha subunit Kv1.2. Most of them were large and medium, although there was a variety of sizes. Peripheral nerve injury caused by lumbar (L)5 spinal nerve ligation (SNL) produced a time-dependent reduction in the number of Kv1.2-positive neurons in the ipsilateral L5 DRG, but not in the contralateral L5 DRG. Such reduction was also observed in the ipsilateral L5 DRG on day 7 after sciatic nerve axotomy. Rescuing nerve injury-induced reduction of Kv1.2 in the injured L5 DRG attenuated the development and maintenance of SNL-induced pain hypersensitivity without affecting acute pain and locomotor function. This effect might be attributed to the prevention of SNL-induced upregulation of endogenous Kv1.2 antisense RNA, in addition to the increase in Kv1.2 protein expression, in the injured DRG. Our findings suggest that Kv1.2 may be a novel potential target for preventing and/or treating neuropathic pain.
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