Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Nuevo Leon, Mexico.
Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
J Neurotrauma. 2023 May;40(9-10):883-900. doi: 10.1089/neu.2022.0238. Epub 2022 Oct 31.
Chronic, often intractable, pain is caused by neuropathic conditions such as traumatic peripheral nerve injury (PNI) and spinal cord injury (SCI). These conditions are associated with alterations in gene and protein expression correlated with functional changes in somatosensory neurons having cell bodies in dorsal root ganglia (DRGs). Most studies of DRG transcriptional alterations have utilized PNI models where axotomy-induced changes important for neural regeneration may overshadow changes that drive neuropathic pain. Both PNI and SCI produce DRG neuron hyperexcitability linked to pain, but contusive SCI produces little peripheral axotomy or peripheral nerve inflammation. Thus, comparison of transcriptional signatures of DRGs across PNI and SCI models may highlight pain-associated transcriptional alterations in sensory ganglia that do not depend on peripheral axotomy or associated effects such as peripheral Wallerian degeneration. Data from our rat thoracic SCI experiments were combined with meta-analysis of published whole-DRG RNA-seq datasets from prominent rat PNI models. Striking differences were found between transcriptional responses to PNI and SCI, especially in regeneration-associated genes (RAGs) and long noncoding RNAs (lncRNAs). Many transcriptomic changes after SCI also were found after corresponding sham surgery, indicating they were caused by injury to surrounding tissue, including bone and muscle, rather than to the spinal cord itself. Another unexpected finding was of few transcriptomic similarities between rat neuropathic pain models and the only reported transcriptional analysis of human DRGs linked to neuropathic pain. These findings show that DRGs exhibit complex transcriptional responses to central and peripheral neural injury and associated tissue damage. Although only a few genes in DRG cells exhibited similar changes in expression across all the painful conditions examined here, these genes may represent a core set whose transcription in various DRG cell types is sensitive to significant bodily injury, and which may play a fundamental role in promoting neuropathic pain.
慢性且常难以治疗的疼痛是由神经病理性疾病引起的，例如创伤性周围神经损伤（PNI）和脊髓损伤（SCI）。这些病症与基因和蛋白质表达的改变有关，这些改变与感觉神经元的功能变化相关，这些神经元的细胞体位于背根神经节（DRG）中。大多数 DRG 转录变化的研究都使用了 PNI 模型，其中轴突切断诱导的变化对于神经再生很重要，可能会掩盖导致神经病理性疼痛的变化。PNI 和 SCI 都会导致 DRG 神经元过度兴奋与疼痛相关，但挫伤性 SCI 很少引起周围轴突切断或周围神经炎症。因此，比较 PNI 和 SCI 模型中 DRG 的转录特征可能会突出与疼痛相关的感觉神经节转录变化，而这些变化不依赖于周围轴突或相关的影响，如周围的华勒氏变性。我们的大鼠胸 SCI 实验数据与来自著名大鼠 PNI 模型的已发表的全 DRG RNA-seq 数据集的荟萃分析相结合。在对 PNI 和 SCI 的转录反应之间发现了明显的差异，特别是在与再生相关的基因（RAGs）和长非编码 RNA（lncRNAs）中。在 SCI 后还发现了许多转录组变化，这些变化在相应的假手术后也出现了，这表明它们是由周围组织（包括骨骼和肌肉）的损伤引起的，而不是由脊髓本身引起的。另一个意外的发现是，大鼠神经病理性疼痛模型之间以及与神经病理性疼痛相关的唯一报道的人类 DRG 转录分析之间很少有转录组相似性。这些发现表明，DRG 对中枢和周围神经损伤以及相关组织损伤表现出复杂的转录反应。尽管在此处检查的所有疼痛条件下，只有少数 DRG 细胞中的基因表现出相似的表达变化，但这些基因可能代表一个核心基因集，其在各种 DRG 细胞类型中的转录对重要的身体损伤敏感，并且可能在促进神经病理性疼痛方面发挥着重要作用。
