Department of Neurology, The First Affiliated Hospital of USTC, 17 Lujiang Road, Hefei, 230001, Anhui Province, China.
Department of Dermatology, The First Affiliated Hospital of USTC, 17 Lujiang Road, Hefei, 230001, Anhui Province, China.
Mol Cell Biochem. 2021 Sep;476(9):3461-3468. doi: 10.1007/s11010-021-04169-3. Epub 2021 May 12.
Postherpetic neuralgia (PHN) is the most common complication of acute herpes zoster. The treatment of PHN remains a challenge for clinical pain management. The present study investigated the P2X7 receptor antagonist brilliant blue G (BBG) whether inhibits endoplasmic reticulum stress and pyroptosis (a necrotic form of cell death) and alleviates PHN. Varicella zoster virus (VZV)-infected CV-1 cells were used to induce PHN model. Mechanical paw withdrawal thresholds were measured using an ascending series of von Frey filaments. Immunohistochemistry was used to detect the expression of P2X7R in nerve tissues. Western blot was used to determine the expression of endoplasmic reticulum (ER) stress and pyroptosis-related molecules. The expression of IL-1β and IL-18 in tissue homogenate was detected by ELISA. The PHN rat has the lower paw withdrawal threshold, but higher expression of P2X7 in nerve tissues. And, endoplasmic reticulum stress was activated and pyroptosis was increased in PHN rats. BBG can decrease pain thresholds and reduce ER stress and pyroptosis in PHN rats. In addition, ER stress activator tunicamycin (TM) can reverse the effect of BBG on the paw withdrawal thresholds, endoplasmic reticulum stress, and pyroptosis. Therefore, P2X7 receptor antagonist BBG alleviates PHN by activating ER stress and reducing pyroptosis.
带状疱疹后神经痛 (PHN) 是急性带状疱疹最常见的并发症。PHN 的治疗仍然是临床疼痛管理的挑战。本研究探讨了 P2X7 受体拮抗剂亮蓝 G (BBG) 是否抑制内质网应激和细胞焦亡（一种坏死形式的细胞死亡）并缓解 PHN。使用单纯疱疹病毒 (VZV) 感染的 CV-1 细胞诱导 PHN 模型。使用一系列升序 von Frey 纤维测量机械性足底撤回阈值。免疫组织化学用于检测神经组织中 P2X7R 的表达。Western blot 用于确定内质网 (ER) 应激和细胞焦亡相关分子的表达。通过 ELISA 检测组织匀浆中 IL-1β 和 IL-18 的表达。PHN 大鼠的足底撤回阈值较低，但神经组织中 P2X7 的表达较高。此外，PHN 大鼠的内质网应激被激活，细胞焦亡增加。BBG 可降低疼痛阈值，并减少 PHN 大鼠的内质网应激和细胞焦亡。此外，内质网应激激活剂衣霉素 (TM) 可逆转 BBG 对足底撤回阈值、内质网应激和细胞焦亡的影响。因此，P2X7 受体拮抗剂 BBG 通过激活内质网应激和减少细胞焦亡来缓解 PHN。
