加巴喷丁对大鼠背根神经节神经元高电压激活钙电流的影响

目的 探讨加巴喷丁对正常大鼠与神经病理性痛大鼠不同损伤部位的背根神经节神经元高电压激活(HVA)钙电流的影响及其原因.方法 雄性SD大鼠,周龄4～6周,采用左侧L5脊神经结扎(SNL)术制备大鼠神经病理性痛模型.于结扎后第14天时采用酶消化法急性分离结扎侧L4背根神经节神经元(SNL-L4组)、L5背根神经节神经元(SNL-L5组),另取正常大鼠L4,5背根神经节神经元作为对照组.采用全细胞膜片钳技术记录加巴喷丁对3组神经元HVA钙电流的作用.结果 在10、100、300 μmol/L浓度下,加巴喷丁对SNL-L5组峰值钙电流的抑制率(18.5±1.7)%、(32.0±2.6)%、(32.7±2.8)%]高于SNL-L4组(16.0±1.9)%、(26.9±2.0)%、(27.4±2.3)%]和对照组(均P<0.05).加巴喷丁作用后,SNL-L5组钙通道稳态失活曲线向超级化方向移动幅度较其他两组明显.与其他两组比较,SNL-L5组加巴喷丁敏感性钙电流中N型钙电流比例升高(均P<0.05).结论 加巴喷丁对神经病理性痛大鼠L5背根神经节神经元HVA钙电流的抑制作用增强,其可能与神经损伤后钙通道激活特性的改变以及N型钙电流比例的升高有关.

Abstract：

Objective To compare the effects of gabapentin on high-voltage-activated calcium (HVA) current in dorsal root ganglion (DRG) neurons in normal and nerve-injured rats and understand the reasons of their differences. Methods Pathogen-free male SD rats(weight 180-220 mg)aged 4-6 weeks were used. The animals were anesthetized with intraperitoneal pentobarbital sodium 50 mg/kg. L5 spinal nerve was ligated between DRG and sciatic nerve and cut distal to the ligature. The animals were decapitated at Day 14 post-operation. L5 (SNL-L5 group) and L4 DRGs (SNL-L4 group) were respectively isolated and the ganglionic neurons enzymatically dissociated. The control group of rats was not operated. The lumbar DRG neurons of normal rats were treated similarly. The HVA-Ca2+ current was recorded by the technique of whole cell patch clamp. Results Compared with the SNL-L4 group (16.0±1.9)%, (26.9±2.0)%, (27.4±2.3)%] and the control group, gabapentin inhibited the peak calcium current highlier at 10, 100 and 300 μmol/L in the SNL-L5 group (18.5±1.7)%, (32.0±2.6)%, (32.7±2.8)%] (P<0.05). The steady-state inactivation curves shifted to more hyperpolarized potentials in the SNL-L5 group. The N-type relative contribution to the gabapentin-sensitive HVA-Ca2+ current was markedly elevated in the SNL-L5 group compared with that in other two groups (P<0.05). Conclusion Gabapentin enhances the inhibition of HVA-Ca2+ current in injured DRG neurons following spinal nerve ligation in rats. The alteration in the activation of electrophysiological properties and the increase of N-type relative contribution to the total HVA-Ca2+ current may be involved in the mechanism.

Effects of gabapentin on high-voltage-activated calcium current in dorsal root ganglion neurons in rats

Objective To compare the effects of gabapentin on high-voltage-activated calcium (HVA) current in dorsal root ganglion (DRG) neurons in normal and nerve-injured rats and understand the reasons of their differences. Methods Pathogen-free male SD rats(weight 180-220 mg)aged 4-6 weeks were used. The animals were anesthetized with intraperitoneal pentobarbital sodium 50 mg/kg. L5 spinal nerve was ligated between DRG and sciatic nerve and cut distal to the ligature. The animals were decapitated at Day 14 post-operation. L5 (SNL-L5 group) and L4 DRGs (SNL-L4 group) were respectively isolated and the ganglionic neurons enzymatically dissociated. The control group of rats was not operated. The lumbar DRG neurons of normal rats were treated similarly. The HVA-Ca2+ current was recorded by the technique of whole cell patch clamp. Results Compared with the SNL-L4 group (16.0±1.9)%, (26.9±2.0)%, (27.4±2.3)%] and the control group, gabapentin inhibited the peak calcium current highlier at 10, 100 and 300 μmol/L in the SNL-L5 group (18.5±1.7)%, (32.0±2.6)%, (32.7±2.8)%] (P<0.05). The steady-state inactivation curves shifted to more hyperpolarized potentials in the SNL-L5 group. The N-type relative contribution to the gabapentin-sensitive HVA-Ca2+ current was markedly elevated in the SNL-L5 group compared with that in other two groups (P<0.05). Conclusion Gabapentin enhances the inhibition of HVA-Ca2+ current in injured DRG neurons following spinal nerve ligation in rats. The alteration in the activation of electrophysiological properties and the increase of N-type relative contribution to the total HVA-Ca2+ current may be involved in the mechanism.