Anesthesiology Department, Civil Aviation General Hospital, Beijing, 100123, People's Republic of China.
Chinese PLA Medical School, Beijing, 100853, China.
BMC Anesthesiol. 2023 Jan 13;23(1):22. doi: 10.1186/s12871-022-01913-0.
The simultaneous use of drugs with different mechanisms of analgesic action is a strategy for achieving effective pain control while minimizing dose-related side effects. Choline was described to potentiate the analgesic action of parecoxib sodium at small doses in several inflammatory pain models. However, these findings are still very limited, and more associated data are required to confirm the effectiveness of the combined choline and parecoxib sodium therapy against inflammatory pain.
Adult rats were randomly divided into 9 groups (N = 6/group). The sham surgery group received an intraperitoneal (i.p.) injection of saline. Rats with chronic constriction injury (CCI) of the sciatic nerve received saline, choline (cho, 6, 12 and 24 mg/kg), parecoxib sodium (pare, 3, 6, and 12 mg/kg), or a combination of choline 6 mg/kg and parecoxib sodium 3 mg/kg. Mechanical and heat pain thresholds were measured at 30 min after drug treatment at Days 3, 5, 7, 10, and 14 after CCI. Another 30 rats were divided into 5 groups (N = 6/group): the sham, CCI + saline, CCI + cho-6 mg/kg, CCI + pare-3 mg/kg, and CCI + cho-6 mg/kg + pare-3 mg/kg groups. After repeated drug treatment for 7 days, five rats were randomly selected from each group, and the lumbar dorsal root ganglia (DRGs) (L4-6) were harvested for western blot analysis.
Choline significantly attenuated mechanical and heat hypersensitivity in CCI rats at 12 and 24 mg/kg doses (P < 0.05) but was not effective at the 6 mg/kg dose. Parecoxib sodium exerted significant pain inhibitory effects at the 6 and 12 mg/kg doses (P < 0.05) but not at the 3 mg/kg dose. Combining a low dose of choline (6 mg/kg) and parecoxib sodium (3 mg/kg) produced significant pain inhibition in CCI rats and reduced the expression of high mobility group protein 1 (HMGB1) and nuclear factor-kappa Bp65 (NF-κBp65) in L4-6 DRGs.
同时使用具有不同镇痛作用机制的药物是实现有效疼痛控制同时最小化剂量相关副作用的策略。在几种炎症性疼痛模型中，已描述小剂量的胆碱可增强帕瑞昔布钠的镇痛作用。然而，这些发现仍然非常有限，需要更多相关数据来证实联合应用胆碱和帕瑞昔布钠治疗炎症性疼痛的有效性。
成年大鼠随机分为 9 组（每组 6 只）。假手术组接受腹腔（i.p.）注射生理盐水。坐骨神经慢性缩窄损伤（CCI）大鼠接受生理盐水、胆碱（cho，6、12 和 24mg/kg）、帕瑞昔布钠（pare，3、6 和 12mg/kg）或 6mg/kg 胆碱和 3mg/kg 帕瑞昔布钠的组合。在 CCI 后第 3、5、7、10 和 14 天，在药物治疗后 30 分钟测量机械和热痛阈值。另外 30 只大鼠分为 5 组（每组 6 只）：假手术组、CCI+生理盐水组、CCI+cho-6mg/kg 组、CCI+pare-3mg/kg 组和 CCI+cho-6mg/kg+pare-3mg/kg 组。在重复药物治疗 7 天后，从每组中随机选择 5 只大鼠，收获腰椎背根神经节（DRGs）（L4-6）进行 Western blot 分析。
在 12 和 24mg/kg 剂量时，胆碱显著减轻 CCI 大鼠的机械和热敏性（P<0.05），但在 6mg/kg 剂量时无效。帕瑞昔布钠在 6 和 12mg/kg 剂量时表现出显著的镇痛作用（P<0.05），但在 3mg/kg 剂量时无效。低剂量胆碱（6mg/kg）和帕瑞昔布钠（3mg/kg）联合应用可显著抑制 CCI 大鼠的疼痛，并降低 L4-6DRGs 中高迁移率族蛋白 1（HMGB1）和核因子-κBp65（NF-κBp65）的表达。
