Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100710, China.
Chin Med J (Engl). 2011 Dec;124(24):4304-9.
Gabapentin has been widely and successfully used in the clinic for many neuropathic pain syndromes since last decade, however its analgesic mechanisms are still elusive. Our study was to investigate whether Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) contributes to the analgesic effect of gabapentin on a chronic constriction injury (CCI) model.
Gabapentin (2%, 100 mg/kg) or saline (0.5 ml/100 g) was injected intraperitoneally 15 minutes prior to surgery and then every 12 hours from postoperative day 0 - 4 to all rats in control, sham and CCI groups. The analgesic effect of gabapentin was assessed by measuring mechanical allodynia and thermal hyperalgesia of rats. Expression and activation of CaMKII were quantified by reverse-transcriptional polymerase chain reaction and Western blotting.
The analgesic effect of gabapentin on mechanical allodynia and thermal hyperalgesia was significant in the CCI model, with maximal reduction reached on postoperative day 8. Gabapentin decreased the expression of the total CaMKII and phosphorylated CaMKII in CCI rats.
The analgesic effect of gabapentin on CCI rats may be related to the decreased expression and phosphorylation of CaMKII in the spinal cord.
加巴喷丁自上世纪以来已广泛并成功应用于多种神经性疼痛综合征的临床治疗，但它的镇痛机制仍不明确。本研究旨在探讨钙/钙调蛋白依赖性蛋白激酶 II（CaMKII）是否参与加巴喷丁对慢性缩窄性损伤（CCI）模型的镇痛作用。
CCI 模型大鼠于术前 15 分钟腹腔内注射加巴喷丁（2%，100mg/kg）或生理盐水（0.5ml/100g），术后第 0-4 天每天腹腔内注射 12 小时，对照组、假手术组和 CCI 组大鼠均给予相应处理。通过测量机械性痛觉过敏和热痛觉超敏评估加巴喷丁的镇痛效果。通过逆转录聚合酶链反应和 Western blot 定量检测 CaMKII 的表达和激活。
加巴喷丁对 CCI 大鼠的机械性痛觉过敏和热痛觉超敏有显著的镇痛作用，最大缓解效果出现在术后第 8 天。加巴喷丁降低了 CCI 大鼠脊髓中总 CaMKII 和磷酸化 CaMKII 的表达。
加巴喷丁对 CCI 大鼠的镇痛作用可能与脊髓中 CaMKII 的表达和磷酸化降低有关。
