Reductions in tonic GABAergic current in substantia gelatinosa neurons and GABAA receptor subunit expression after chronic constriction injury of the sciatic nerve in mice
Reductions in tonic GABAergic current in substantia gelatinosa neurons and GABAA receptor subunit expression after chronic constriction injury of the sciatic nerve in mice
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DOI：
10.1002/ejp.891
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发表时间：
2016-11-01
影响因子：
3.6
通讯作者：
Fujino, Y.
中科院分区：
文献类型：
--
作者：
Iura, A.;Takahashi, A.;Fujino, Y.
研究背景脊髓内γ-氨基丁酸（GABA）能时相抑制性传递的减少被认为是神经病理性疼痛发生的原因。然而，胶状质（SG）神经元GABA能紧张性电流在神经病理性疼痛中的作用仍有待充分阐明。在这项研究中，我们评估了GABA能紧张性电流在坐骨神经慢性压迫性损伤（CCI）小鼠SG神经元在腰段脊髓切片的全细胞膜片钳记录，以评估GABA能电流。我们还研究了GABA（A）受体亚单位的表达变化，这些亚单位被认为是介导紧张性电流的。结果CCI小鼠接受GABA能紧张性电流的SG神经元的百分比较Naive小鼠减少。GABA能紧张性电流的平均幅度无显著变化。结论CCI后小鼠SG神经元GABA（A）受体亚单位表达减少，GABA能紧张性电流减弱。GABA能紧张性电流在神经病理性疼痛中起关键作用。GABA（A）受体亚单位可能是神经病理性疼痛的治疗靶点。这项研究增加了什么？在脊髓SG神经元中，GABA能抑制性传递通过相位电流和强直电流进行，但生理作用在很大程度上是未知的。在这项研究中，我们报告的GABA（A）受体亚单位介导的紧张性电流在SG神经元的失调可能会导致脊髓去抑制导致CCI小鼠的神经病理性疼痛。
BackgroundDecreased Gamma-aminobutyric acid (GABA)-ergic phasic inhibitory transmission in the spinal cord is thought to be responsible for the development of neuropathic pain. However, the role of GABAergic tonic current in substantia gelatinosa (SG) neurons in neuropathic pain remains to be fully elucidated. In this study, we assessed GABAergic tonic currents of SG neurons in a sciatic nerve chronic constriction injury (CCI) mouse.MethodWhole-cell patch clamp recordings form lumbar spinal cord slices was performed to evaluate GABAergic currents. We also investigated the expression changes of GABA(A) receptor subunits which are considered to mediate tonic currents.ResultsThe percentage of SG neurons receiving GABAergic tonic currents decreased in CCI mice compared with Naive mice. No significant change was observed in the mean amplitude of GABAergic tonic currents. RT-PCR and Western blot revealed that the expression of GABA(A) receptor subunits decreased following CCI.ConclusionA reduction in the expression the subunit of the GABA(A) receptor and diminished GABAergic tonic current in SG neurons were observed after CCI in mice. GABAergic tonic current plays a key role in neuropathic pain. The GABA(A) receptor subunit may be a therapeutic target in neuropathic pain.What does this study add?In spinal SG neurons, GABAergic inhibitory transmission operates through both phasic and tonic currents, but physiological role is largely unknown. In this study, we report dysregulation of GABA(A) receptor subunit-mediated tonic current in SG neurons may result in spinal disinhibition resulting in neuropathic pain in CCI mice.