AMPA受体和NMDA受体在leptin参与神经病理性痛机制中的作用

Roles of AMPA Receptors and NMDA Receptors in Mechanism of Leptin Involved in Neuropathic Pain

【目的】观察离子型谷氨酸受体AMPA受体和NMDA受体在leptin参与神经病理性痛机制中的作用。【方法】用膜片钳全细胞模式记录leptin是否影响正常大鼠脊髓切片背角Ⅱ层神经元AMPA受体和NMDA受体介导的电流;大鼠鞘内注射leptin,持续14 d,在第1,3,7,14天检测热痛阈和机械痛阈。在第14天处死动物,用免疫组化法和western blot检测脊髓背角AMPA受体和NMDA受体的表达。【结果】灌流液中加入leptin能增加NMDA受体介导的电流,并有剂量依赖性,100nmol/L leptin的作用最显著,leptin对AMPA受体介导的电流无影响;大鼠鞘内注射leptin,在第14天明显降低热痛阈和机械痛阈;leptin增加了脊髓背角NMDA受体亚单位NR1的表达,但是对AMPA受体亚单位GluR1的表达无影响。NMDA受体拮抗剂MK-801可抑制并逆转leptin诱导的痛行为及抑制leptin诱导的NR1表达增多。【结论】Leptin可能通过影响NMDA受体参与神经病理性痛的发生。

[Objective] To investigate the roles of AMPA receptors and NMDA receptors in the mechanism of leptin involved in neuropathie pain. [ Methods ] The effect of leptin on AMPA receptors and NMDA receptors induced-currents were record by whole-cell clamp recording in dorsal horn lamina Ⅱ neurons of adult SD rats. Mechanical allodynia and thermal hyperalgesia were measured on day 1, 3, 7, and 14 after intrathecal injection of leptin （50μg） in naive rats, given once daily for 14 days. On day 14, all the rats were killed and the expression of AMPA receptors and NMDA receptors were measured. [ Results ] Leptin dose-dependently enhanced NMDA-induced current, among which 100 nmol/L concentration had the maximal enhancement effect. Leptin had no effect on AMPA-induced current. Intratheeal injection of leptin （50 pig） in naive rats induced mechanical allodynia and theimal hyperalgesia on day 14. The behavioral changes were prevented and reversed by NMDA receptor antagonist MK-801. Moreover, intrathecal injection of leptin increased the expression of NMDA receptors subunit NR1 on dorsal horn, which was also blocked by MK-801 but had no effect on AMPA receptors subunit GluR1. [ Conclusion ] Leptin may involved the mechanisms of neuropathic pain through NMDA receptors.