Shen Shiren, Cao Su, Huang Saisai, Chen Junjie
Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, China.
Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, China.
J Surg Res. 2015 May 15;195(2):481-7. doi: 10.1016/j.jss.2015.01.033. Epub 2015 Jan 28.
Alterations in adenosine triphosphate-sensitive potassium (KATP) activity and expression under changing physiological conditions are important adaptive and protective mechanisms. KATP subunit expression is also altered in neuropathic pain; whether these changes are adaptive or deleterious is unclear. We therefore established a skin/muscle incision and retraction (SMIR) rat model of postoperative pain and examined the relationship between pain sensitization and changes in KATP subunit expression.
Rats were randomly divided into untreated, sham-operation, SMIR, and SMIR + Pinacidil (sulfonylurea receptor [SUR]2-activator) groups. In the SMIR group, skin and muscle were retracted for 1 h after incision. In the SMIR + Pinacidil group, Pinacidil was injected intraperitoneally 0.5 h before SMIR or into the spinal myelin sheath 7 d after SMIR. Mechanical withdrawal threshold was used as an index of pain sensitivity. Expression levels and localization of the KATP subunits Kir6.2, Kir6.1, SUR1, and SUR2 were measured by Western blotting and immunofluorescence.
A rat postoperative pain model was successfully established, in which SMIR induced mechanical hypersensitivity (allodynia). Notably, significantly increased Kir6.1, Kir6.2, SUR1, and SUR2 protein expression levels were observed in tissues around the incision (P < 0.05). In addition, significantly decreased Kir6.1, SUR2, and SUR1 protein levels were obtained in spinal cord L3-L5. SMIR also starkly increased nerve growth factor expression in the muscle around the incision. Importantly, intrathecal Pinacidil injection inhibited the overexpression of allodynia markers and nerve growth factor.
Hyperexcitability due to spinal Kir6.1 and SUR2 downregulation may be responsible for postoperative pain. SUR2 activation is a potential strategy to inhibit postoperative allodynia.
在生理条件变化时，三磷酸腺苷敏感性钾通道（KATP）活性和表达的改变是重要的适应性和保护机制。KATP亚基表达在神经性疼痛中也会发生改变；这些变化是适应性的还是有害的尚不清楚。因此，我们建立了术后疼痛的皮肤/肌肉切开并牵拉（SMIR）大鼠模型，并研究了疼痛敏化与KATP亚基表达变化之间的关系。
将大鼠随机分为未处理组、假手术组、SMIR组和SMIR + 吡那地尔（磺脲类受体[SUR]2激活剂）组。在SMIR组中，切开皮肤和肌肉后牵拉1小时。在SMIR + 吡那地尔组中，在SMIR前0.5小时腹腔注射吡那地尔，或在SMIR后7天注射到脊髓髓鞘内。以机械缩足阈值作为疼痛敏感性指标。通过蛋白质印迹法和免疫荧光法检测KATP亚基Kir6.2、Kir6.1、SUR1和SUR2的表达水平及定位。
成功建立了大鼠术后疼痛模型，其中SMIR诱导了机械性超敏反应（痛觉过敏）。值得注意的是，在切口周围组织中观察到Kir6.1、Kir6.2、SUR1和SUR2蛋白表达水平显著升高（P < 0.05）。此外，在脊髓L3 - L5中，Kir6.1、SUR2和SUR1蛋白水平显著降低。SMIR还显著增加了切口周围肌肉中神经生长因子的表达。重要的是，鞘内注射吡那地尔可抑制痛觉过敏标志物和神经生长因子的过表达。
脊髓中Kir6.1和SUR2下调导致的兴奋性过高可能是术后疼痛的原因。激活SUR2是抑制术后痛觉过敏的一种潜在策略。
