Gong Shan, Liang Qian, Zhu Qi, Ding Dayong, Yin Qizhang, Tao Jin, Jiang Xinghong
Department of Physiology and Neurobiology, Key Laboratory of Pain Research and Therapy, Medical College of Soochow University, PR China.
Department of Physiology and Neurobiology, Key Laboratory of Pain Research and Therapy, Medical College of Soochow University, PR China.
Toxicon. 2015 Jan;93:31-6. doi: 10.1016/j.toxicon.2014.11.222. Epub 2014 Nov 6.
In this study we report that cobratoxin (CbTX), a long-chain postsynaptic α-neurotoxin isolated from the Thailand cobra, Naja naja kaouthia, has antinociceptive effect in rats with neuropathic pain. The neuropathic pain model was established in rats with partial sciatic nerve ligature (PSNL) method. The pain response was examined behaviorally with mechanical paw withdrawal and thermal paw withdrawal method. Different doses (0.56, 1.12 and 4.50 μg/kg) of CbTX were injected intrathecally. Injection of CbTX resulted in a significant dose-dependent antinociception as evidenced by increased mechanical withdrawal threshold and thermal withdrawal latency. CbTX also induces a significant dose-dependent inhibition of pain-evoked unit discharges of thalamic parafascicular neurons. Both the behavioral mechanical and thermal antinociception and the inhibition of pain-evoked discharges of neurons in thalamic parafascicular nucleus in PSNL model could be mimicked by PUN282987, selective α7 nicotinic AChR (α7 nAChR) agonist and reversed by methyllycaconitine (MLA) selective α7 nAChR antagonist. In summary, these results suggested that AChR α7 subunit was involved in the antinociceptive action of CbTX for neuropathic pain and might be the candidate target for analgesic drug design.
在本研究中，我们报告从泰国眼镜蛇（眼镜王蛇）分离出的一种长链突触后α-神经毒素——眼镜蛇毒素（CbTX），对患有神经性疼痛的大鼠具有镇痛作用。采用部分坐骨神经结扎（PSNL）法在大鼠中建立神经性疼痛模型。通过机械性缩爪和热缩爪方法对疼痛反应进行行为学检测。将不同剂量（0.56、1.12和4.50μg/kg）的CbTX鞘内注射。注射CbTX导致显著的剂量依赖性镇痛作用，表现为机械性缩爪阈值增加和热缩爪潜伏期延长。CbTX还诱导丘脑束旁核神经元疼痛诱发单位放电的显著剂量依赖性抑制。PSNL模型中行为学上的机械性和热性镇痛以及丘脑束旁核神经元疼痛诱发放电的抑制，均可被选择性α7烟碱型乙酰胆碱受体（α7 nAChR）激动剂PUN282987模拟，并被选择性α7 nAChR拮抗剂甲基lycaconitine（MLA）逆转。总之，这些结果表明AChR α7亚基参与了CbTX对神经性疼痛的镇痛作用，可能是镇痛药物设计的候选靶点。
