College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
Int J Mol Sci. 2024 Sep 24;25(19):10242. doi: 10.3390/ijms251910242.
Neuropathic pain (NPP) is a devastating and unbearable painful condition. As prevailing treatment strategies have failed to mitigate its complications, there remains a demand for effective therapies. Electroacupuncture (EA) has proved a potent remedial strategy in NPP management in humans and mammals. However, past studies have investigated the underlying mechanism of the analgesic effects of EA on NPP, focusing primarily on adenosine receptors in peripheral tissues. Herein, we elucidate the role of the adenosine (Adora-3) signaling pathway in mediating pain relief through EA in the central nervous system, which is obscure in the literature and needs exploration. Specific pathogen-free (SPF) male adult mice (C57BL/6 J) were utilized to investigate the effect of EA on adenosine metabolism (CD73, ADA) and its receptor activation (Adora-3), as potential mechanisms to mitigate NPP in the central nervous system. NPP was induced via spared nerve injury (SNI). EA treatment was administered seven times post-SNI surgery, and lumber (L4-L6) spinal cord was collected to determine the molecular expression of mRNA and protein levels. In the spinal cord of mice, following EA application, the expression results revealed that EA upregulated ( < 0.05) Adora-3 and CD73 by inhibiting ADA expression. In addition, EA triggered the release of adenosine (ADO), which modulated the nociceptive responses and enhanced neuronal activation. Meanwhile, the interplay between ADO levels and EA-induced antinociception, using an Adora-3 agonist and antagonist, showed that the Adora-3 agonist IB-MECA significantly increased ( < 0.05) nociceptive thresholds and expression levels. In contrast, the antagonist MRS1523 exacerbated neuropathic pain. Furthermore, an upregulated effect of EA on Adora-3 expression was inferred when the Adora-3 antagonist was administered, and the EA treatment increased the fluorescent intensity of Adora-3 in the spinal cord. Taken together, EA effectively modulates NPP by regulating the Adora-3 signaling pathway under induced pain conditions. These findings enhance our understanding of NPP management and offer potential avenues for innovative therapeutic interventions.
神经病理性疼痛（NPP）是一种破坏性的、难以忍受的疼痛状态。由于现有的治疗策略未能减轻其并发症，因此仍然需要有效的治疗方法。电针（EA）已被证明是人类和哺乳动物 NPP 管理中的一种有效治疗策略。然而，过去的研究主要集中在外周组织中的腺苷受体上，探讨了 EA 对 NPP 的镇痛作用的潜在机制。在此，我们阐明了在中枢神经系统中，通过 EA 介导的疼痛缓解的腺苷（Adora-3）信号通路的作用，这在文献中尚不清楚，需要进一步探索。使用特定病原体（SPF）雄性成年小鼠（C57BL/6 J）来研究 EA 对腺苷代谢（CD73、ADA）及其受体激活（Adora-3）的影响，这是潜在的减轻中枢神经系统 NPP 的机制。通过 spared 神经损伤（SNI）诱导 NPP。在 SNI 手术后进行 7 次 EA 治疗，并收集腰椎（L4-L6）脊髓以确定 mRNA 和蛋白水平的分子表达。在小鼠脊髓中，EA 应用后，表达结果显示 EA 通过抑制 ADA 表达而上调（<0.05）Adora-3 和 CD73。此外，EA 触发了腺苷（ADO）的释放，调节了伤害性反应并增强了神经元激活。同时，使用 Adora-3 激动剂和拮抗剂观察 ADO 水平与 EA 诱导的抗伤害作用之间的相互作用，结果表明 Adora-3 激动剂 IB-MECA 显著增加（<0.05）伤害性阈值和表达水平。相比之下，拮抗剂 MRS1523 加重了神经病理性疼痛。此外，当给予 Adora-3 拮抗剂时，推断出 EA 对 Adora-3 表达的上调作用，并且 EA 治疗增加了脊髓中 Adora-3 的荧光强度。总之，EA 通过在诱导疼痛条件下调节 Adora-3 信号通路，有效调节 NPP。这些发现提高了我们对 NPP 管理的理解，并为创新的治疗干预提供了潜在途径。
