Qian Li-Ping, Shen Shi-Ren, Chen Jun-Jie, Ji Lu-Lu, Cao Su
Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
Mol Med Rep. 2016 Sep;14(3):2632-8. doi: 10.3892/mmr.2016.5546. Epub 2016 Jul 27.
The aim of the current study was to assess the effect of pinacidil activation of ATP‑sensitive potassium (KATP) channels prior to skin/muscle incision and retraction (SMIR) surgery on peripheral and central sensitization, and investigate molecular interferential targets for preventive analgesia. Male Sprague-Dawley rats were randomly assigned to one of the following five groups: Control, incision (sham surgery), incision plus retraction (SMIR) group, SMIR plus pinacidil (pinacidil) group and the SMIR plus pyrrolidine dithiocarbamate (PDTC) group. The rats in the pinacidil and PDTC groups were intraperitoneally injected with pinacidil or PDTC, respectively, prior to the SMIR procedure. The mechanical withdrawal threshold (MWT) was determined. Western blotting was performed to detect the alterations in the subunits of the KATP channels, Kir6.1 and SUR2, levels of nuclear factor‑κB (NF‑κB) in the tissue around the incision and c‑Jun N‑terminal kinase (JNK) in the spinal cord. There was a significant increase observed in the levels of NF‑κB and JNK following SMIR surgery compared with the control group, and a significant reduction in MWT and the levels of Kir6.1 and SUR2. Additionally, intraperitoneal administration of pinacidil inhibited the reduction in MWT, and Kir6.1 and SUR2 levels. SMIR was observed to result in increases in the levels of NF‑κB and JNK. In addition, in the PDTC group, the alterations in MWT, NF‑κB, JNK, Kir6.1 and SUR2 resulting from SMIR were blocked. The results of the current study suggest that the deteriorations in the microenvironment resulting from the SMIR procedure can induce peripheral and central sensitization, and that the activation of peripheral KATP by pinacidil prior to SMIR is able to inhibit peripheral and central sensitization via the NF‑κB/JNK signaling pathway, thus resulting in preventive analgesia.
本研究的目的是评估在皮肤/肌肉切开和牵拉（SMIR）手术前使用吡那地尔激活三磷酸腺苷敏感性钾（KATP）通道对周围和中枢敏化的影响，并研究预防性镇痛的分子干预靶点。将雄性Sprague-Dawley大鼠随机分为以下五组之一：对照组、切开（假手术）组、切开加牵拉（SMIR）组、SMIR加吡那地尔（吡那地尔）组和SMIR加吡咯烷二硫代氨基甲酸盐（PDTC）组。在SMIR手术前，吡那地尔组和PDTC组的大鼠分别腹腔注射吡那地尔或PDTC。测定机械缩足阈值（MWT）。采用蛋白质免疫印迹法检测KATP通道亚基Kir6.1和SUR2、切口周围组织中核因子-κB（NF-κB）水平以及脊髓中c-Jun氨基末端激酶（JNK）的变化。与对照组相比，SMIR手术后NF-κB和JNK水平显著升高，MWT以及Kir6.1和SUR2水平显著降低。此外，腹腔注射吡那地尔可抑制MWT以及Kir6.1和SUR水平的降低。观察到SMIR导致NF-κB和JNK水平升高。此外，在PDTC组中，SMIR引起的MWT、NF-κB、JNK、Kir6.1和SUR2的变化被阻断。本研究结果表明，SMIR手术导致的微环境恶化可诱导周围和中枢敏化，且在SMIR手术前用吡那地尔激活外周KATP能够通过NF-κB/JNK信号通路抑制周围和中枢敏化，从而产生预防性镇痛作用。
