Transcript Expression of Vesicular Glutamate Transporters in Rat Dorsal Root Ganglion and Spinal Cord Neurons: Impact of Spinal Blockade during Hindpaw Inflammation.,ACS Chemical Neuroscience

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Transcript Expression of Vesicular Glutamate Transporters in Rat Dorsal Root Ganglion and Spinal Cord Neurons: Impact of Spinal Blockade during Hindpaw Inflammation.
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2020-07-22 , DOI: 10.1021/acschemneuro.0c00272
Candelaria Leiguarda ₁ , Carly J McCarthy ₁ , Mailin Casadei ₁ , Kerstin H Lundgren ₂ , María Florencia Coronel ₁ , Harry Trigosso-Venario ₃ , Rebecca P Seal ₄ , Kim B Seroogy ₂ , Pablo R Brumovsky ₁

Affiliation

Studies in mouse, and to a lesser extent in rat, have revealed the neuroanatomical distribution of vesicular glutamate transporters (VGLUTs) and begun exposing the critical role of VGLUT2 and VGLUT3 in pain transmission. In the present study in rat, we used specific riboprobes to characterize the transcript expression of all three VGLUTs in lumbar dorsal root ganglia (DRGs) and in the thoracolumbar, lumbar, and sacral spinal cord. We show for the first time in rat a very discrete VGLUT3 expression in DRGs and in deep layers of the dorsal horn. We confirm the abundant expression of VGLUT2, in both DRGs and the spinal cord, including presumable motorneurons in the latter. As expected, VGLUT1 was present in many DRG neuron profiles, and in the spinal cord it was mostly localized to neurons in the dorsal nucleus of Clarke. In rats with a 10 day long hindpaw inflammation, increased spinal expression of VGLUT2 transcript was detected by qRT-PCR, and intrathecal administration of the nonselective VGLUT inhibitor Chicago Sky Blue 6B resulted in reduced mechanical and thermal allodynia for up to 24 h. In conclusion, our results provide a collective characterization of VGLUTs in rat DRGs and the spinal cord, demonstrate increased spinal expression of VGLUT2 during chronic peripheral inflammation, and support the use of spinal VGLUT blockade as a strategy for attenuating inflammatory pain.

中文翻译：

大鼠背根神经节和脊髓神经元中囊状谷氨酸转运蛋白的转录表达：后足炎症过程中脊髓阻滞的影响。

在小鼠中以及在较小程度上在大鼠中进行的研究，揭示了水泡谷氨酸转运蛋白（VGLUTs）的神经解剖学分布，并开始揭示VGLUT2和VGLUT3在疼痛传递中的关键作用。在当前的大鼠研究中，我们使用特定的核糖核酸来表征腰背根神经节（DRG）和胸腰，腰椎和and脊髓中所有三个VGLUT的转录表达。我们首次在大鼠中显示了在DRG和背角深层中非常离散的VGLUT3表达。我们证实在DRG和脊髓中均包含VGLUT2的大量表达，包括后者中可能的运动神经元。正如预期的那样，VGLUT1存在于许多DRG神经元特征中，并且在脊髓中它大部分位于Clarke背核的神经元中。在具有10天长后足炎症的大鼠中，通过qRT-PCR检测到VGLUT2转录物的脊髓表达增加，并且鞘内注射非选择性VGLUT抑制剂Chicago Sky Blue 6B导致长达24小时的机械和热异常性疼痛减少。总之，我们的结果提供了大鼠DRG和脊髓中VGLUT的集体特征，证明了慢性外周炎症期间VGLUT2的脊髓表达增加，并支持使用脊髓VGLUT阻断作为减轻炎症性疼痛的策略。

更新日期：2020-09-02

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