绿原酸对紫杉醇致小鼠外周神经痛的影响

Effect of Chlorogenic Acid on Peripheral Neuropathic Pain Induced by Paclitaxel

目的研究绿原酸对紫杉醇引起小鼠外周神经痛的影响,并初步探讨其电生理机制。方法小鼠腹腔注射紫杉醇(4mg/kg)建立外周神经痛模型,采用Up-down法检测小鼠足底机械痛阈。采用膜片钳技术记录背根神经节神经元(DRG)动作电位。结果小鼠腹腔注射四次紫杉醇(4mg/kg,0、2、4、6d注射)可显著降低足底机械痛阈,建立小鼠外周神经痛模型。在小鼠首次注射紫杉醇的第9d,腹腔给予不同剂量(10mg/kg、30mg/kg和100mg/kg)的绿原酸处理,中、高剂量(30mg/kg和100mg/kg)的绿原酸处理后15~30min可明显地缓解紫杉醇引起的外周神经痛敏(P<0.01),而低剂量(10mg/kg)的绿原酸对机械痛敏没有影响。电流钳记录小鼠DRG神经元去极化引起的动作电位,与对照组小鼠DRG神经元比较,紫杉醇致外周神经痛小鼠DRG神经元去极化引起的动作电位数量显著增多(P<0.01);但绿原酸预处理可减少外周神经痛小鼠DRG神经元去极化引起的动作电位数量(P<0.05)。结论绿原酸可以减轻紫杉醇引起的小鼠外周神经痛,其机制可能与其降低DRG神经元的兴奋性有关。

Objective To study the effect of chlorogenic acid on paclitaxel-induced peripheral neuropathic pain in mice and to further explore its electrophygical mechanism. Methods Peripheral neuropathic pain model was established by intraperitoneal injection of paclitaxel (4mg/kg) in mice.The mechanical threshold was measured by the "Up-down" method.Action potentials were recorded by patch clamp technique in mouse dorsal root ganglion (DRG) neurons. Results After mice were injected intraperitoneally (i.p.) with 4mg/kg paclitaxel (days 0、2、4 and 6),the mechanical pain threshold of the mice was significantly reduced,which indicated that the peripheral neuropathic pain model was established.On the 9th day after the first injection of paclitaxel in mice,different doses of chlorogenic acid (10mg/kg,30mg/kg and 100mg/kg) were administered intraperitoneally.The paclitaxel-induced pain sensitization was significantly alleviated 15~30 minutes after treatment with medium and high doses (30mg/kg and 100mg/kg) of chlorogenic acid ( P <0.01),while low doses (10mg/kg) of chlorogenic acid had no effect on mechanical pain threshold.Current clamp was used to record action potentials induced by depolarization in mouse DRG neurons.The number of action potentials was significantly increased in DRG neurons from mice with paclitaxel-induced peripheral neuropathic pain,compared with that from control mice,( P <0.01).After chlorogenic acid was pre-applied to DRG neurons from mice with peripheral neuropathic pain,the number of depolarization-evoked action potentials was significantly decreased ( P <0.05). Conclusion Chlorogenic acid can alleviate paclitaxel-induced peripheral neuropathic pain in mice,which may involve in lowering the excitability of DRG neurons.