Zhang Yanbo, Gong Kerui, Zhou Weihua, Shao Guo, Li Sijie, Lin Qing, Li Jingjin
Department of Neurology, the Affiliated Hospital of Taishan Medical College, Tai'an, China.
Neurosignals. 2011;19(3):142-50. doi: 10.1159/000328311. Epub 2011 Jun 23.
Protein kinase C (PKC) has been widely reported to participate in somatic pain; however, its role in visceral pain remains largely unclear. Using a colon inflammatory pain model by intracolonic injection of formalin in rats, the present study was to examine the role of PKC in visceral pain and determine which subtypes may be involved. The colon pain behavior induced by formalin injection could be enhanced by intrathecal pretreatment with a PKC activator (PMA), and alleviated by a PKC inhibitor (H-7). Wide dynamic range (WDR) neurons in the L6-S1 spinal dorsal horn that were responsive to colorectal distension were recorded extracellularly. It was found that neuronal activity was greatly increased following formalin injection. Microdialysis of PMA near the recorded neuron in the spinal dorsal horn facilitated the enhanced responsive activity induced by formalin injection, while H-7 inhibited significantly the enhanced response induced by formalin injection. Western blot analysis revealed that membrane translocation of PKC-γ and PKC-ε, but not other subtypes, in the spinal cord was obviously increased following formalin injection. Therefore, our findings suggest that PKC is actively involved in the colon pain induced by intracolonic injection of formalin. PKC-γ and PKC-ε subtypes seem to significantly contribute to this process.
蛋白激酶C(PKC)已被广泛报道参与躯体疼痛;然而,其在内脏痛中的作用仍不清楚。本研究采用大鼠结肠内注射福尔马林建立结肠炎性疼痛模型,以研究PKC在内脏痛中的作用,并确定可能涉及的亚型。鞘内预先注射PKC激活剂(PMA)可增强福尔马林注射诱导的结肠疼痛行为,而PKC抑制剂(H-7)则可减轻该行为。细胞外记录L6-S1脊髓背角中对结直肠扩张有反应的广动力范围(WDR)神经元。发现福尔马林注射后神经元活动显著增加。在脊髓背角记录神经元附近微量注射PMA可促进福尔马林注射诱导的反应性活动增强,而H-7则显著抑制福尔马林注射诱导的反应增强。蛋白质印迹分析显示,福尔马林注射后脊髓中PKC-γ和PKC-ε而非其他亚型的膜转位明显增加。因此,我们的研究结果表明PKC积极参与结肠内注射福尔马林诱导的结肠疼痛。PKC-γ和PKC-ε亚型似乎对这一过程有显著贡献。