Institute of Molecular Medicine, The Feinstein Institutes for Medical Research, Manhasset, NY, USA.
Donald and Barbara Zucker School of Medicine at Hofstra-Northwell, Hempstead, NY, USA.
Mol Pain. 2021 Jan-Dec;17:17448069211007289. doi: 10.1177/17448069211007289.
Pain affects most individuals with traumatic spinal cord injury (SCI). Major pain types after SCI are neuropathic or nociceptive, often experienced concurrently. Pain after SCI may be refractory to treatments and negatively affects quality of life. Previously, we analyzed whole blood gene expression in individuals with chronic SCI compared to able-bodied (AB) individuals. Most participants with SCI reported pain (N = 19/28). Here, we examined gene expression of participants with SCI by pain status. Compared to AB, participants with SCI with pain had 468 differentially expressed (DE) genes; participants without pain had 564 DE genes (FDR < 0.05). Among DE genes distinct to participants with SCI with pain, Gene Ontology Biological Process (GOBP) analysis showed upregulated genes were enriched in categories related to T cell activation or inflammation; downregulated genes were enriched in categories related to protein proteolysis and catabolism. Although most participants with pain reported multiple pain types concurrently, we performed a preliminary comparison of gene expression by worst pain problem type. Compared to AB, participants with SCI who ranked neuropathic (N = 9) as worst had one distinct DE gene (TMEM156); participants who ranked nociceptive (N = 10) as worst had 61 distinct DE genes (FDR < 0.05). In the nociceptive group, the GOBP category with the lowest P-value identified among upregulated genes was "positive regulation of T cell activation"; among downregulated genes it was "receptor tyrosine kinase binding". An exploratory comparison of pain groups by principal components analysis also showed that the nociceptive group was enriched in T-cell related genes. A correlation analysis identified genes significantly correlated with pain intensity in the neuropathic or nociceptive groups (N = 145, 65, respectively, Pearson's correlation r > 0.8). While this pilot study highlights challenges of identifying gene expression profiles that correlate with specific types of pain in individuals with SCI, it suggests that T-cell signaling should be further investigated in this context.
疼痛影响大多数创伤性脊髓损伤（SCI）患者。SCI 后的主要疼痛类型为神经病理性或伤害感受性，通常同时存在。SCI 后的疼痛可能对治疗有抗药性，并对生活质量产生负面影响。此前，我们分析了慢性 SCI 患者与健全（AB）个体的全血基因表达。大多数 SCI 患者（N=19/28）报告有疼痛。在这里，我们根据疼痛状况检查了 SCI 患者的基因表达。与 AB 相比，有疼痛的 SCI 患者有 468 个差异表达（DE）基因；没有疼痛的 SCI 患者有 564 个 DE 基因（FDR<0.05）。在有疼痛的 SCI 患者中独特的 DE 基因中，基因本体论生物过程（GOBP）分析显示上调基因富集在与 T 细胞激活或炎症相关的类别中；下调基因富集在与蛋白质水解和分解代谢相关的类别中。尽管大多数有疼痛的患者同时报告了多种疼痛类型，但我们根据最严重的疼痛问题类型对基因表达进行了初步比较。与 AB 相比，将神经病理性（N=9）列为最严重的 SCI 患者有一个独特的 DE 基因（TMEM156）；将伤害感受性（N=10）列为最严重的 SCI 患者有 61 个独特的 DE 基因（FDR<0.05）。在伤害感受性组中，上调基因中最低 P 值的 GOBP 类别是“T 细胞激活的正调控”；下调基因中是“受体酪氨酸激酶结合”。通过主成分分析对疼痛组进行的探索性比较也表明，伤害感受性组富含与 T 细胞相关的基因。相关性分析确定了神经病理性或伤害感受性组中与疼痛强度显著相关的基因（N=145，65，分别为 Pearson 相关性 r>0.8）。虽然这项初步研究强调了在 SCI 患者中确定与特定类型疼痛相关的基因表达谱的挑战，但它表明在这种情况下应进一步研究 T 细胞信号传导。
