Nerve injury elevates functional Cav3.2 channels in superficial spinal dorsal horn
Nerve injury elevates functional Cav3.2 channels in superficial spinal dorsal horn
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神经损伤提升浅表脊髓背角的功能性 Cav3.2 通道
DOI：
10.1177/1744806919836569
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发表时间：
2019-04-09
期刊：
影响因子：
3.3
通讯作者：
Liu, Tao
中科院分区：
文献类型：
--
作者：
Feng, Xiao-Jin;Ma, Long-Xian;Liu, Tao
Cav3通道在调节慢性疼痛中起重要作用。然而，对神经病理性疼痛状态下脊髓背角浅层Cav3通道的功能变化知之甚少。在这里，我们研究了部分坐骨神经结扎（PSNL）对浅层脊髓背角Cav3通道的表达或电生理特性的影响。我们的体内研究表明，Cav 3通道阻滞剂可以强烈缓解PSNL诱导的机械性异常性疼痛和热痛敏，这些疼痛在PSNL后至少持续14天。同时，PSNL引发了大鼠Cav3.2的mRNA和蛋白水平的增加，而不是Cav3.1或Cav3.3。然而，在Cav3.2基因敲除小鼠中，PSNL主要减弱机械性异常性疼痛，但不减弱热痛觉过敏。此外，全细胞膜片钳记录的结果表明，无论是整体比例的Cav3电流表达的神经元和单个神经元中的Cav3电流密度升高脊髓板层II神经元从PSNL大鼠，这不能重现Cav3.2基因敲除小鼠。总之，我们的研究结果表明，在PSNL诱导的神经病理性疼痛模型中，脊髓背角浅层功能性Cav3.2通道的升高可能有助于机械异常性疼痛。
Cav3 channels play an important role in modulating chronic pain. However, less is known about the functional changes of Cav3 channels in superficial spinal dorsal horn in neuropathic pain states. Here, we examined the effect of partial sciatic nerve ligation (PSNL) on either expression or electrophysiological properties of Cav3 channels in superficial spinal dorsal horn. Our in vivo studies showed that the blockers of Cav3 channels robustly alleviated PSNL-induced mechanical allodynia and thermal hyperalgesia, which lasted at least 14 days following PSNL. Meanwhile, PSNL triggered an increase in both mRNA and protein levels of Cav3.2 but not Cav3.1 or Cav3.3 in rats. However, in Cav3.2 knockout mice, PSNL predominantly attenuated mechanical allodynia but not thermal hyperalgesia. In addition, the results of whole-cell patch-clamp recordings showed that both the overall proportion of Cav3 current-expressing neurons and the Cav3 current density in individual neurons were elevated in spinal lamina II neurons from PSNL rats, which could not be recapitulated in Cav3.2 knockout mice. Altogether, our findings reveal that the elevated functional Cav3.2 channels in superficial spinal dorsal horn may contribute to the mechanical allodynia in PSNL-induced neuropathic pain model.