Song Yu, Zhu Jun-Sheng, Hua Rong, Du Lei, Huang Si-Ting, Stackman Robert W, Zhang Gongliang, Zhang Yong-Mei
Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China.
Emergency Department, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Front Pharmacol. 2018 Aug 3;9:840. doi: 10.3389/fphar.2018.00840. eCollection 2018.
Visceral hypersensitivity is a highly complex and subjective phenomenon associated with multiple levels of the nervous system and a wide range of neurotransmission. The dorsal horn (DH) in spinal cord relays the peripheral sensory information into the brain. Small conductance Ca-activated K (SK) channels regulate neuronal excitability and firing by allowing K to efflux in response to increase in the intracellular Ca level. In this study, we examined the influence of SK2 channels in the spinal DH on the pathogenesis of visceral hypersensitivity induced by colorectal distension (CRD) in rats. Electrophysiological results showed that rats with visceral hypersensitivity presented a decrease in the SK channel-mediated afterhyperpolarization current (), and an increase in neuronal firing rates and -Fos positive staining in the spinal DH. Western blot data revealed a decrease in the SK2 channel protein in the membrane fraction. Moreover, intrathecal administration of the SK2 channel activator 1-EBIO or CyPPA alleviated visceral hypersensitivity, reversed the decrease in and the increase in neuronal firing rates in spinal DH in rats that experienced CRD. 1-EBIO or CyPPA effect could be prevented by SK2 channel blocker apamin. CRD induced an increase in -Fos protein expression in the spinal DH, which was prevented by 1-EBIO. Together, these data suggest that visceral hypersensitivity and pain is associated with a decrease in the number and function of membrane SK2 channels in the spinal DH. Pharmacological manipulation of SK2 channels may open a new avenue for the treatment of visceral hypersensitivity and pain. -Neonatal colorectal distension induced visceral hypersensitivity in rats.-Visceral hypersensitivity rats presented a decrease in afterhyperpolarization current () and membrane SK2 channel protein in the spinal dorsal horn.-Visceral hypersensitivity rats presented an increase in neuronal firing rate in the spinal dorsal horn.-Intrathecal administration of SK2 channel activator 1-EBIO or CyPPA prevented visceral hypersensitivity and decrease in .
内脏高敏感性是一种高度复杂且主观的现象，与神经系统的多个层面及广泛的神经传递相关。脊髓背角（DH）将外周感觉信息传递至大脑。小电导钙激活钾（SK）通道通过允许钾离子外流以响应细胞内钙水平的升高来调节神经元兴奋性和放电。在本研究中，我们研究了脊髓背角中SK2通道对大鼠结直肠扩张（CRD）诱导的内脏高敏感性发病机制的影响。电生理结果显示，内脏高敏感性大鼠的SK通道介导的超极化后电流（）降低，脊髓背角神经元放电率增加且Fos阳性染色增多。蛋白质印迹数据显示膜组分中SK2通道蛋白减少。此外，鞘内注射SK2通道激活剂1-EBIO或CyPPA可减轻内脏高敏感性，逆转CRD大鼠脊髓背角中降低及神经元放电率增加的情况。SK2通道阻滞剂蜂毒明肽可阻断1-EBIO或CyPPA的作用。CRD诱导脊髓背角中Fos蛋白表达增加，1-EBIO可预防此现象。总之，这些数据表明内脏高敏感性和疼痛与脊髓背角中膜SK2通道数量和功能的降低有关。对SK2通道进行药理学调控可能为内脏高敏感性和疼痛的治疗开辟新途径。 -新生大鼠结直肠扩张诱导内脏高敏感性。-内脏高敏感性大鼠脊髓背角的超极化后电流（）和膜SK2通道蛋白减少。-内脏高敏感性大鼠脊髓背角的神经元放电率增加。-鞘内注射SK2通道激活剂1-EBIO或CyPPA可预防内脏高敏感性和降低。
