College of Chinese Medicine, Graduate Institute of Acupuncture Science, China Medical University, Taichung, 40402, Taiwan.
College of Chinese Medicine, Graduate Institute of Integrated Medicine, China Medical University, Taichung, 40402, Taiwan.
Sci Rep. 2017 Apr 25;7:46663. doi: 10.1038/srep46663.
Many scientists are seeking better therapies for treating fibromyalgia (FM) pain. We used a mouse model of FM to determine if ASIC3 and its relevant signaling pathway participated in FM pain. We demonstrated that FM-induced mechanical hyperalgesia was attenuated by electroacupuncture (EA). The decrease in fatigue-induced lower motor function in FM mice was also reversed by EA. These EA-based effects were abolished by the opioid receptor antagonist naloxone and the adenosine A1 receptor antagonist rolofylline. Administration of opioid receptor agonist endomorphin (EM) or adenosine A1 receptor agonist N-cyclopentyladenosine (CPA) has similar results to EA. Similar results were also observed in ASIC3 or ASIC3 antagonist (APETx2) injected mice. Using western blotting, we determined that pPKA, pPI3K, and pERK were increased during a dual acidic injection priming period. Nociceptive receptors, such as ASIC3, Nav1.7, and Nav1.8, were upregulated in the dorsal root ganglion (DRG) and spinal cord (SC) of FM mice. Furthermore, pPKA, pPI3K, and pERK were increased in the central thalamus. These aforementioned mechanisms were completely abolished in ASIC3 knockout mice. Electrophysiological results also indicated that acid potentiated Nav currents through ASIC3 and ERK pathway. Our results highlight the crucial role of ASIC3-mediated mechanisms in the treatment of FM-induced mechanical hyperalgesia.
许多科学家正在寻找更好的治疗纤维肌痛 (FM) 疼痛的疗法。我们使用 FM 小鼠模型来确定 ASIC3 及其相关信号通路是否参与 FM 疼痛。我们表明，电针对 FM 诱导的机械性痛觉过敏具有缓解作用。电针还逆转了 FM 小鼠因疲劳引起的下运动功能下降。纳洛酮（一种阿片受体拮抗剂）和罗洛非林（一种腺苷 A1 受体拮抗剂）可消除这些基于电针的效应。阿片受体激动剂内吗啡（EM）或腺苷 A1 受体激动剂 N-环戊基腺苷（CPA）的给药也具有与电针类似的效果。在注射 ASIC3 或 ASIC3 拮抗剂（APETx2）的小鼠中也观察到了类似的结果。通过 Western blot，我们确定在双重酸性注射引发期 pPKA、pPI3K 和 pERK 增加。在 FM 小鼠的背根神经节 (DRG) 和脊髓 (SC) 中，痛觉受体（如 ASIC3、Nav1.7 和 Nav1.8）上调。此外，pPKA、pPI3K 和 pERK 在中央丘脑增加。这些上述机制在 ASIC3 敲除小鼠中完全被消除。电生理结果还表明，酸通过 ASIC3 和 ERK 通路增强了 Nav 电流。我们的结果强调了 ASIC3 介导的机制在治疗 FM 诱导的机械性痛觉过敏中的关键作用。
