Laboratory of Approches expérimentales et Thérapeutiques des Douleurs Neuropathiques, 133 route de Narbonne, 31062 Toulouse, France.
Neurosci Res. 2011 Feb;69(2):111-20. doi: 10.1016/j.neures.2010.10.006. Epub 2010 Oct 21.
Current understanding of chronic pain points a decrease in level of the inhibitory neurotransmitter GABA, in the spinal dorsal horn, leading to an imbalance between excitatory and inhibitory pathways. A subcloned derivative of the human NT2 cell line (hNT2.17) which, after neuronal differentiation, secretes different inhibitory neurotransmitters such as GABA and glycine has been recently isolated. In this study, we have investigated the effect of this new cell line on peripheral nerve injury induced by chronic constriction (CCI) and notably the effect on the cellular GABAergic pathway. Our data show that the decrease in GABA expression in the spinal dorsal horn of injured animals is concomitant with a decline of its synthetic enzyme GAD67-Ir and mRNA but not GAD65. Interestingly, in transplanted animals we observed a strong induction of GAD67 mRNA with one week after graft, which is followed by a recovery of GAD67 and GABA Ir. This effect paralleled a reduction of hindpaw hypersensitivity and thermal hyperalgesia induced by CCI. These results suggest that hNT2.17 GABA cells can modulate neuropathic pain after CCI certainly by minimizing the imbalance and restoring the cellular GABAergic pathway.
目前对慢性疼痛的理解指向脊髓背角抑制性神经递质 GABA 水平下降，导致兴奋和抑制途径失衡。最近分离出了人 NT2 细胞系（hNT2.17）的一个亚克隆衍生物，该细胞系在神经元分化后会分泌不同的抑制性神经递质，如 GABA 和甘氨酸。在这项研究中，我们研究了这种新细胞系对慢性缩窄性损伤（CCI）引起的周围神经损伤的影响，特别是对细胞 GABA 能途径的影响。我们的数据表明，损伤动物脊髓背角中 GABA 表达的减少伴随着其合成酶 GAD67-Ir 和 mRNA 的下降，但 GAD65 没有下降。有趣的是，在移植动物中，我们观察到移植后一周 GAD67 mRNA 强烈诱导，随后 GAD67 和 GABA Ir 恢复。这种效应与 CCI 引起的后爪过敏和热痛觉过敏的减少相平行。这些结果表明，hNT2.17 GABA 细胞可以通过最小化失衡和恢复细胞 GABA 能途径来调节 CCI 后的神经病理性疼痛。
