Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, the Fourth Military Medical University, the 127(th) West Changle Road, Xi'an, 710032, Shaanxi, China; Department of Central Laboratory, the General Hospital of Western Theater Command, the 270(th)Tianhui Road, Chengdu, 610083, Sichuan, China.
Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, the Fourth Military Medical University, the 127(th) West Changle Road, Xi'an, 710032, Shaanxi, China.
Neuroscience. 2019 Apr 15;404:499-509. doi: 10.1016/j.neuroscience.2019.02.028. Epub 2019 Mar 1.
Under pathological conditions, acupoint sensitization is the phenomenon of acupoints transforming from the stable state to the dynamic state. Evidences suggest that hyperpolarization-activated current (I), conducted by the hyperpolarization-activated/cyclic nucleotide-gated (HCN) channel, greatly contributes to the peripheral and central sensitization. However, the role of the I current in acupoint sensitization has not been explained. In the present study, changes in excitability, I density and the HCN channel of dorsal root ganglion (DRG) nociceptive neurons were examined in the later phase of knee osteoarthritis (KOA) rats. To investigate the neuronal specificity of acupoint sensitization, retrograde dyes were injected into the acupoints ST35 and GB37. The results showed that acupoint sensitization occurred in bilateral ST35 but not GB37 acupoints. The excitability and I density of C- but not A-type neurons innervating ST35 acupoint increased in bilateral L5 DRG of acupoint sensitized rats than that of sham rats. No obvious changes were found in the excitability or I density of C- and A-type neurons innervating the GB37 acupoint in the bilateral L5 DRG. HCN channel subtype 2 (HCN2) expression levels significantly increased after acupoint sensitization. Furthermore, ZD7288, an HCN current (I) blocker, attenuated the acupoint sensitization of the ST35 acupoint. Taken together, our findings suggest that the increased excitability of C- but not A-type neurons and the upregulation of I/HCN2 channels contribute to the formation of acupoint sensitization.
在病理条件下，穴位敏化是穴位从稳定状态转变为动态状态的现象。有证据表明，超极化激活电流（I），由超极化激活/环核苷酸门控（HCN）通道传导，对周围和中枢敏化有很大贡献。然而，I 电流在穴位敏化中的作用尚未得到解释。在本研究中，检查了膝骨关节炎（KOA）大鼠后期背根神经节（DRG）伤害性神经元的兴奋性、I 密度和 HCN 通道的变化。为了研究穴位敏化的神经元特异性，将逆行染料注入穴位 ST35 和 GB37。结果表明，双侧 ST35 出现穴位敏化，但双侧 GB37 穴位未出现穴位敏化。与 sham 大鼠相比，双侧 L5 DRG 中支配 ST35 穴位的 C 型而非 A 型神经元的兴奋性和 I 密度增加。在双侧 L5 DRG 中支配 GB37 穴位的 C 型和 A 型神经元的兴奋性或 I 密度没有明显变化。HCN 通道亚型 2（HCN2）表达水平在穴位敏化后显著增加。此外，ZD7288，一种 HCN 电流（I）阻断剂，可减轻 ST35 穴位的穴位敏化。总之，我们的研究结果表明，C 型而非 A 型神经元兴奋性的增加和 I/HCN2 通道的上调有助于穴位敏化的形成。
