Dong Rong, Yu Buwei, Chen Lijiao, Yu Weifeng
Department of Anesthesiology, Eastern Hepatobiliary Hospital, The Second Military Medical University, Shanghai 200438, P.R. China; Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
Exp Ther Med. 2016 Dec;12(6):3583-3588. doi: 10.3892/etm.2016.3807. Epub 2016 Oct 14.
Postoperative pain is a critical problem in clinical pain administration. Due to the unclear formation mechanism of postoperative pain, the treatment of postoperative pain is still in the symptomatic treatment stage and lacking satisfactory analgesic effect. Postoperative pain can be simulated by using a rat incision pain model. We observed changes in pain-related behavior of rats affected by the 5-hydroxytryptamine 2A receptor (5-HTR) agonist, TCB-2, and antagonist, ketanserin, through intrathecal delivery. The transcription and translation level of potassium-chloride cotransporter 2 (KCC2) in the spinal cord was also measured to investigate the role of the 5-HTR-KCC2 pathway in the mechanism of incision pain. Compared with the control group, rats in the incision pain group had decreased mechanical withdrawal threshold (MWT), with significant differences on day 1-7 after surgery, and significant decreases in thermal withdrawal latency (TWL) on days 1, 2, 3 and 6 (P<0.05). Compared with the incision + dimethyl sulfoxide (DMSO) group, MWT and TWL decreased in the incision + ketanserin group on day 1 and 2 (P<0.05). There was no significant difference detected in TWL of incision + TCB-2 group on day 1, while MWT increased significantly compared to the incision + DMSO group (P<0.05). Furthermore, the transcription and translation levels of KCC2 in the incision + ketanserin group decreased significantly in comparison to the incision + DMSO group (P<0.05), while an increase was detected in the incision + TCB-2 group (P<0.05). MWT and TWL decreased in the incision pain rats, accompanied with a decreased transcription and translation level of KCC2. Intrathecal delivery of the 5-HTR agonist, TCB-2, alleviated the decreased WMT and inhibited the decreased transcription and translation level of KCC2, while intrathecal delivery of the 5-HTR antagonist, ketanserin, aggravated the decreased WMT and transcription and translation levels of KCC2, suggesting the involement of the 5-HTR-KCC2 pathway in the formation mechanism of incision pain in rats.
术后疼痛是临床疼痛管理中的一个关键问题。由于术后疼痛的形成机制尚不清楚，术后疼痛的治疗仍处于对症治疗阶段，且缺乏令人满意的镇痛效果。可以通过使用大鼠切口疼痛模型来模拟术后疼痛。我们通过鞘内给药观察了5-羟色胺2A受体（5-HTR）激动剂TCB-2和拮抗剂酮色林对大鼠疼痛相关行为的影响。还测量了脊髓中氯化钾共转运体2（KCC2）的转录和翻译水平，以研究5-HTR-KCC2通路在切口疼痛机制中的作用。与对照组相比，切口疼痛组大鼠的机械缩足阈值（MWT）降低，在术后第1-7天有显著差异，在第1、2、3和6天热缩足潜伏期（TWL）显著缩短（P<0.05）。与切口+二甲基亚砜（DMSO）组相比，切口+酮色林组在第1天和第2天MWT和TWL降低（P<0.05）。切口+TCB-2组在第1天TWL无显著差异，而MWT与切口+DMSO组相比显著增加（P<0.05）。此外，与切口+DMSO组相比，切口+酮色林组KCC2的转录和翻译水平显著降低（P<0.05），而切口+TCB-2组则升高（P<）。切口疼痛大鼠的MWT和TWL降低，同时KCC2的转录和翻译水平降低。鞘内注射5-HTR激动剂TCB-缓解了MWT的降低，并抑制了KCC2转录和翻译水平的降低，而鞘内注射5-HTR拮抗剂酮色林则加剧了MWT以及KCC2转录和翻译水平的降低，提示5-HTR-KCC2通路参与了大鼠切口疼痛的形成机制。 05）。切口疼痛大鼠的MWT和TWL降低，同时KCC2的转录和翻译水平降低。鞘内注射5-HTR激动剂TCB-2缓解了MWT的降低，并抑制了KCC2转录和翻译水平的降低，而鞘内注射5-HTR拮抗剂酮色林则加剧了MWT以及KCC2转录和翻译水平的降低，提示5-HTR-KCC2通路参与了大鼠切口疼痛的形成机制。
