Role of dorsal root ganglion K2p1.1 in peripheral nerve injury-induced neuropathic pain.
Role of dorsal root ganglion K2p1.1 in peripheral nerve injury-induced neuropathic pain.
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DOI：
10.1177/1744806917701135
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发表时间：
2017-01
期刊：
影响因子：
3.3
通讯作者：
Tao YX
中科院分区：
文献类型：
--
作者：
Mao Q;Yuan J;Ming X;Wu S;Chen L;Bekker A;Yang T;Tao YX
周围神经损伤引起的背根神经节（DRG）初级感觉神经元的过度兴奋和异常异位放电在神经病理性疼痛的发生和维持中起着关键作用。双孔结构域背景钾（K2P）通道已被确定为静息膜电位和神经元兴奋性的关键决定因素。然而，K2P通道是否有助于神经病理性疼痛仍然是难以捉摸的。我们在这里报道，K2P1.1，第一个确定的哺乳动物K2P通道，在小鼠DRG中高度表达，并分布在小，中，大尺寸的DRG神经元。单侧L4脊神经结扎导致同侧L4 DRG中K2P1.1 mRNA和蛋白的显著和时间依赖性减少，但在对侧L4或同侧L3 DRG中没有。通过将表达全长K2P1.1 mRNA的腺相关病毒DJ显微注射到同侧L4 DRG中来挽救这种减少，在开发和维护期间阻断了脊神经结扎诱导的机械，热和冷痛超敏反应。这种DRG病毒显微注射不影响急性疼痛和运动功能。我们的研究结果表明，K2P1.1参与神经病理性疼痛的发展和维持，并可能是一个潜在的目标，在这种疾病的管理。
Peripheral nerve injury-caused hyperexcitability and abnormal ectopic discharges in the primary sensory neurons of dorsal root ganglion (DRG) play a key role in neuropathic pain development and maintenance. The two-pore domain background potassium (K2P) channels have been identified as key determinants of the resting membrane potential and neuronal excitability. However, whether K2P channels contribute to neuropathic pain is still elusive. We reported here that K2P1.1, the first identified mammalian K2P channel, was highly expressed in mouse DRG and distributed in small-, medium-, and large-sized DRG neurons. Unilateral lumbar (L) 4 spinal nerve ligation led to a significant and time-dependent reduction of K2P1.1 mRNA and protein in the ipsilateral L4 DRG, but not in the contralateral L4 or ipsilateral L3 DRG. Rescuing this reduction through microinjection of adeno-associated virus-DJ expressing full-length K2P1.1 mRNA into the ipsilateral L4 DRG blocked spinal nerve ligation-induced mechanical, thermal, and cold pain hypersensitivities during the development and maintenance periods. This DRG viral microinjection did not affect acute pain and locomotor function. Our findings suggest that K2P1.1 participates in neuropathic pain development and maintenance and may be a potential target in the management of this disorder.