Leiguarda Candelaria, McCarthy Carly J, Casadei Mailin, Lundgren Kerstin H, Coronel María Florencia, Trigosso-Venario Harry, Seal Rebecca P, Seroogy Kim B, Brumovsky Pablo R
Instituto de Investigaciones en Medicina Traslacional (IIMT), CONICET-Austral, Derqui, Pilar B1629AHJ, Buenos Aires, Argentina.
Department of Neurology, University of Cincinnati, Cincinnati, Ohio 45267, United States.
ACS Chem Neurosci. 2020 Sep 2;11(17):2602-2614. doi: 10.1021/acschemneuro.0c00272. Epub 2020 Aug 10.
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.
对小鼠的研究,以及在较小程度上对大鼠的研究,揭示了囊泡谷氨酸转运体(VGLUTs)的神经解剖分布,并开始揭示VGLUT2和VGLUT3在疼痛传递中的关键作用。在本项对大鼠的研究中,我们使用特异性核糖探针来表征腰段背根神经节(DRGs)以及胸腰段、腰段和骶段脊髓中所有三种VGLUTs的转录本表达。我们首次在大鼠中显示DRGs和背角深层中VGLUT3的表达非常离散。我们证实VGLUT2在DRGs和脊髓中均有丰富表达,包括脊髓中可能的运动神经元。正如预期的那样,VGLUT1存在于许多DRG神经元形态中,在脊髓中它主要定位于克拉克背核中的神经元。在患有长达10天的后爪炎症的大鼠中,通过qRT-PCR检测到脊髓中VGLUT2转录本表达增加,鞘内注射非选择性VGLUT抑制剂芝加哥天蓝6B可导致机械性和热性痛觉过敏减轻长达24小时。总之,我们的结果提供了大鼠DRGs和脊髓中VGLUTs的综合表征,证明了慢性外周炎症期间脊髓中VGLUT2表达增加,并支持使用脊髓VGLUT阻断作为减轻炎性疼痛的策略。