Is GABAA receptor involved in trigeminal nociceptive transmission?

介绍;本项目旨在探讨GABAA受体介导的伤害性调节在脊髓或三叉背角的可能参与。我们使用了部分缺失GAGAA受体功能的双敲除小鼠（DKO）。方法和结果：免疫组化研究显示DKO小鼠脊髓浅、深大细胞层细胞表面GABAA受体γ - 2亚基完全缺失。野生动物和DKO动物的MAC分别为1.36±0.04% （n=10）和1.07±0.01% (n=10)（学生t检验，p<0.001）。上述结果提示，γ - 2亚基的刺激可能不会产生抗伤害性作用。第三，膜电位的时空传播和髓质切片细胞内钙浓度的变化在野生动物和DKO动物之间表现出相似的传播特征，并且高选择性GABAA受体激动剂muscimol的灌注没有引起这些传播特征的差异。经BDNF预处理后，传入刺激引起的膜电位传播在肌醇灌注下发生了一定的变化。结论;这些结果表明，正常情况下GABAA受体在痛觉传递中没有明显的调节作用，但一些刺激诱导BDNF释放可能对这种传递特性有一定的调节作用。

Introduction ; This project aimed to investigate the possible involvement of GABAA receptor mediated nociceptive modulation in the spinal or trigeminal dorsal horn. We used PRIP-1, PRIP-2 double knockout mice (DKO) which deficits some GAGAA receptor function.Method and results : Immnunohistochemical study exhibited a complete deficit in γ2 subunit of GABAA receptor on cell surface of the superficial and deep magnocellular layers in spinal cord of DKO mice. The MAC of wild or DKO animal was 1.36±0.04% (n=10) or 1.07±0.01% (n=10), respectively (Student's t-test, p<0.001). These results suggest that the stimulation of γ2 subunit might did not induce anti-nociceptive effect. Thirdly, spatial and temporal propagation of membrane potential and the changes in the intra- cellular calcium concentration in the slice of medulla exhibited the similar propagation between in the wild and DKO animals and furthermore a perfusion of the highly-selective GABAA receptor agonist muscimol did not induce any difference in these propagation features. The preconditioning by BDNF induced some difference in afferent stimulation induced changes in membrane potential propagation under muscimol perfusion.Conclusion ; these results suggest that GABAA receptor does not have any significant role in modulation of nociceptive transmission in normal condition but some stimuli induce BDNF releasing might have some modulating effect on this transmission feature.