Functional Genomics Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Room 130, Bethesda, MD, 20892, USA.
Department of Neuroscience and Center for Advanced Pain Studies, The University of Texas at Dallas, Dallas, TX, 75080, USA.
Sci Rep. 2024 Oct 29;14(1):25893. doi: 10.1038/s41598-024-77212-0.
Autoimmune diseases such as rheumatoid arthritis (RA) can promote states of chronic inflammation with accompanying tissue destruction and pain. RA can cause inflammatory synovitis in peripheral joints, particularly within the hands and feet, but can also sometimes trigger temporomandibular joint (TMJ) arthralgia. To better understand the effects of ongoing inflammation-induced pain signaling, dorsal root ganglia (DRGs) were acquired from individuals with RA for transcriptomic study. We conducted RNA sequencing from the L5 DRGs because it contains the soma of the sensory neurons that innervate the affected joints in the foot. DRGs from 5 RA patients were compared with 9 non-arthritic controls. RNA-seq of L5 DRGs identified 128 differentially expressed genes (DEGs) that were dysregulated in the RA subjects as compared to the non-arthritic controls. The DRG resides outside the blood brain barrier and, as such, our initial transcriptome analysis detected signs of an autoimmune disorder including the upregulated expression of immunoglobulins and other immunologically related genes within the DRGs of the RA donors. Additionally, we saw the upregulation in genes implicated in neurogenesis that could promote pain hypersensitivity. Overall, our DRG analysis suggests that there are upregulated inflammatory and pain signaling pathways that can contribute to chronic pain in RA.
自身免疫性疾病，如类风湿关节炎 (RA)，可引发慢性炎症状态，伴有组织破坏和疼痛。RA 可引起外周关节的炎症性滑膜炎，特别是在手和脚，但有时也可引发颞下颌关节 (TMJ) 关节痛。为了更好地了解持续炎症诱导的疼痛信号的影响，我们从 RA 患者中获取背根神经节 (DRG) 进行转录组研究。我们对 L5 DRG 进行了 RNA 测序，因为它包含了感觉神经元的体，这些神经元支配着足部受影响的关节。将 5 名 RA 患者的 DRG 与 9 名非关节炎对照进行比较。L5 DRG 的 RNA-seq 鉴定出 128 个差异表达基因 (DEG)，与非关节炎对照组相比，RA 患者的这些基因表达失调。DRG 位于血脑屏障之外，因此，我们的初始转录组分析检测到 RA 供体 DRG 中存在自身免疫疾病的迹象，包括免疫球蛋白和其他免疫相关基因的上调表达。此外，我们还观察到与神经发生相关的基因上调，这可能导致疼痛敏感性增加。总的来说，我们的 DRG 分析表明，存在上调的炎症和疼痛信号通路，这可能导致 RA 中的慢性疼痛。
