Fang Junfan, Du Junying, Xiang Xuaner, Shao Xiaomei, He Xiaofeng, Jiang Yongliang, Liu Boyi, Liang Yi, Fang Jianqiao
Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Exp Brain Res. 2021 Mar;239(3):983-995. doi: 10.1007/s00221-020-05988-4. Epub 2021 Jan 19.
Peripheral inflammation and nerve injury usually accompany each other. However, whether inflammatory and neuropathic pain share similar mechanisms at all stages is unknown. TRPV1 and P2X3 are two major ion channels in dorsal root ganglia (DRGs) and are involved in chronic pain. Here, their function and expression in DRGs at different phases of the two types of pain were investigated. Both the paw withdrawal threshold (PWT) and paw withdrawal latency were decreased in rats injected with complete Freud's adjuvant (CFA). However, only the PWT was decreased in rats with spared nerve injury (SNI). CFA increased the magnitude of the TRPV1-mediated Ca response but not the P2X3-mediated Ca response 14 days after injection. Consistent with this result, the P2X3 expression level in CFA rats was increased only at 3 days after injection. SNI surgery increased the magnitudes of the TRPV1- and P2X3-mediated Ca responses and upregulated both TRPV1 and P2X3 expression in lumbar DRGs. The distributions of TRPV1 and P2X3 in DRGs after modeling were observed, and TRPV1 was found to be highly expressed mainly in the L4-L5 DRGs in CFA rats and in the L5-L6 DRGs in SNI rats. P2X3 was highly expressed in the L4-L6 DRGs in CFA rats 3 days after injection but was only highly expressed in the L4 DRG 14 days after modeling. On the other hand, SNI promoted the P2X3 expression L4-L5 DRGs 3 days after surgery, but only L6 DRG 14 days after modeling. All the results indicate that P2X3 and TPRV1 are involved in inflammatory and neuropathic pain by different expression levels and distributions in the lumbar DRG in the chronic stage.
外周炎症和神经损伤通常相伴发生。然而，炎症性疼痛和神经性疼痛在所有阶段是否具有相似机制尚不清楚。TRPV1和P2X3是背根神经节（DRG）中的两个主要离子通道，参与慢性疼痛。在此，研究了它们在两种疼痛不同阶段DRG中的功能和表达。注射完全弗氏佐剂（CFA）的大鼠，其爪部撤离阈值（PWT）和爪部撤离潜伏期均降低。然而，在 spared 神经损伤（SNI）大鼠中，仅PWT降低。注射后14天，CFA增加了TRPV1介导的Ca反应幅度，但未增加P2X3介导的Ca反应幅度。与该结果一致，CFA大鼠中P2X3表达水平仅在注射后3天升高。SNI手术增加了TRPV1和P2X3介导的Ca反应幅度，并上调了腰段DRG中TRPV1和P2X3的表达。观察了建模后DRG中TRPV1和P2X3的分布，发现TRPV1主要在CFA大鼠的L4-L5 DRG和SNI大鼠的L5-L6 DRG中高表达。注射后3天，P2X3在CFA大鼠的L4-L6 DRG中高表达，但建模后14天仅在L4 DRG中高表达。另一方面，SNI在手术后3天促进了L4-L5 DRG中P2X3的表达，但建模后14天仅促进了L6 DRG中P2X3的表达。所有结果表明，在慢性期，P2X3和TPRV1通过腰段DRG中不同的表达水平和分布参与炎症性疼痛和神经性疼痛。
