Department of Diagnostic Sciences, Rutgers School of Dental Medicine, Rutgers, The State University of New Jersey, Newark, NJ, USA.
Office of Advance Research Computing, Rutgers, The State University of New Jersey, Newark, NJ, USA.
Eur J Pain. 2020 May;24(5):967-982. doi: 10.1002/ejp.1546. Epub 2020 Mar 13.
The dorsal root (DRG) and trigeminal (TG) ganglia contain cell bodies of sensory neurons of spinal and trigeminal systems, respectively. They are homologs of each other; however, differences in how the two systems respond to injury exist. Trigeminal nerve injuries rarely result in chronic neuropathic pain (NP). To date, no genes involved in the differential response to nerve injury between the two systems have been identified. We examined transcriptional changes involved in the development of trigeminal and spinal NP.
Trigeminal and spinal mononueropathies were induced by chronic constriction injury to the infraorbital or sciatic nerve. Expression levels of 84 genes in the TG and DRG at 4, 8 and 21 days post-injury were measured using real-time PCR.
We found time-dependent and ganglion-specific transcriptional regulation that may contribute to the development of corresponding neuropathies. Among genes significantly regulated in both ganglia Cnr2, Grm5, Htr1a, Il10, Oprd1, Pdyn, Prok2 and Tacr1 were up-regulated in the TG but down-regulated in the DRG at 4 days post-injury; at 21 days post-injury, Adora1, Cd200, Comt, Maob, Mapk3, P2rx4, Ptger1, Tnf and Slc6a2 were significantly up-regulated in the TG but down-regulated in the DRG.
Our findings suggest that spinal and trigeminal neuropathies due to trauma are differentially regulated. Subtle but important differences between the two ganglia may affect NP development.
We present distinct transcriptional alterations in the TG and DRG that may contribute to differences observed in the corresponding mononeuropathies. Since the trigeminal system seems more resistant to developing NP following trauma our findings lay ground for future research to detect genes and pathways that may act in a protective or facilitatory manner. These may be novel and important therapeutic targets.
背根神经节（DRG）和三叉神经节（TG）包含脊髓和三叉神经系统感觉神经元的细胞体。它们彼此同源；然而，两个系统对损伤的反应存在差异。三叉神经损伤很少导致慢性神经性疼痛（NP）。迄今为止，尚未发现涉及两个系统对神经损伤的差异反应的相关基因。我们研究了与三叉神经和脊髓 NP 发展相关的转录变化。
通过眶下神经或坐骨神经慢性缩窄损伤诱导三叉神经和脊髓单神经病。使用实时 PCR 测量损伤后 4、8 和 21 天 TG 和 DRG 中 84 个基因的表达水平。
我们发现了时间依赖性和神经节特异性的转录调节，这可能有助于相应神经病的发展。在两个神经节中均受到显著调节的基因中，Cnr2、Grm5、Htr1a、Il10、Oprd1、Pdyn、Prok2 和 Tacr1 在 TG 中上调，但在 DRG 中下调 4 天；在 21 天，Adora1、Cd200、Comt、Maob、Mapk3、P2rx4、Ptger1、Tnf 和 Slc6a2 在 TG 中显著上调，但在 DRG 中下调。
我们的发现表明，创伤引起的脊髓和三叉神经神经病受到不同的调节。两个神经节之间的细微但重要的差异可能会影响 NP 的发展。
我们在 TG 和 DRG 中发现了不同的转录变化，这些变化可能有助于解释相应单神经病之间的差异。由于三叉神经系统在创伤后似乎更能抵抗 NP 的发展，我们的研究结果为未来的研究奠定了基础，以检测可能以保护或促进方式作用的基因和途径。这些可能是新的和重要的治疗靶点。
