Department of Pharmacology, University of Iowa, Iowa City, Iowa 52242, USA.
J Comp Neurol. 2012 Jun 1;520(8):1663-77. doi: 10.1002/cne.23005.
This study examined the distribution of γ-aminobutyric acid (GABA)(B) receptors on immunohistochemically identified neurons, and levels of GABA(B(1)) and GABA(B(2)) mRNA, in the L4 and L5 dorsal root ganglia (DRG) of the rat in the absence of injury and 2 weeks after L5 spinal nerve ligation. In uninjured DRG, GABA(B(1)) immunoreactivity colocalized exclusively with the neuronal marker (NeuN) and did not colocalize with the satellite cell marker S-100. The GABA(B(1)) subunit colocalized to >97% of DRG neurons immunoreactive (IR) for neurofilament 200 (N52) or calcitonin gene-related peptide (CGRP), or labeled by isolectin B4 (IB4). Immunoreactivity for GABA(B(2)) was not detectable. L5 spinal nerve ligation did not alter the number of GABA(B(1)) -IR neurons or its colocalization pattern in the L4 DRG. However, ligation reduced the number of GABA(B(1)) -IR neurons in the L5 DRG by ≈38% compared with sham-operated and naïve rats. Specifically, ligation decreased the number of CGRP-IR neurons in the L5 DRG by 75%, but did not decrease the percent colocalization of GABA(B(1)) in those that remained. In the few IB4-positive neurons that remained in the L5 DRG, colocalization of GABA(B(1)) -IR decreased to 75%. Ligation also decreased levels of GABA(B(1)) and GABA(B(2)) mRNA in the L5, but not the L4 DRG compared with sham-operated or naïve rats. These findings indicate that the GABA(B) receptor is positioned to presynaptically modulate afferent transmission by myelinated, unmyelinated, and peptidergic afferents in the dorsal horn. Loss of GABA(B) receptors on primary afferent neurons may contribute to the development of mechanical allodynia after L5 spinal nerve ligation.
本研究旨在探讨在未受伤和 L5 脊神经结扎 2 周后,大鼠 L4 和 L5 背根神经节(DRG)中γ-氨基丁酸(GABA)(B)受体在免疫组织化学鉴定神经元上的分布,以及 GABA(B(1))和 GABA(B(2))mRNA 的水平。在未受伤的 DRG 中,GABA(B(1))免疫反应性仅与神经元标志物(NeuN)特异性共定位,而不与卫星细胞标志物 S-100 共定位。GABA(B(1))亚基与对神经丝 200(N52)或降钙素基因相关肽(CGRP)免疫反应性(IR)的 >97%的 DRG 神经元共定位,或被异凝集素 B4(IB4)标记。GABA(B(2))的免疫反应性无法检测到。L5 脊神经结扎并未改变 L4 DRG 中 GABA(B(1))-IR 神经元的数量或其共定位模式。然而,与假手术和未处理的大鼠相比,结扎使 L5 DRG 中 GABA(B(1))-IR 神经元的数量减少了约 38%。具体来说,结扎使 L5 DRG 中 CGRP-IR 神经元的数量减少了 75%,但并未减少剩余神经元中 GABA(B(1))的共定位比例。在 L5 DRG 中仅存的少数 IB4 阳性神经元中,GABA(B(1))-IR 的共定位减少到 75%。结扎还降低了 L5,但不降低 L4 DRG 中 GABA(B(1))和 GABA(B(2))mRNA 的水平,与假手术或未处理的大鼠相比。这些发现表明,GABA(B)受体定位于背角中的有髓和无髓传入纤维和肽能传入纤维的突触前,以调节传入传递。初级传入神经元上 GABA(B)受体的丧失可能导致 L5 脊神经结扎后机械性痛觉过敏的发展。