Bedir Zehra, Ozkaloglu Erdem Kezban Tuna, Doymus Omer, Suleyman Halis, Yavuzer Bulent, Cicek Betul, Altuner Durdu, Mammadov Renad, Yilmaz Mehmet, Coban Taha Abdulkadir, Suleyman Bahadir, Bulut Seval
Department of Anaesthesiology and Reanimation, University of Health Sciences, Erzurum State Hospital, Erzurum, Türkiye.
Department of Anaesthesiology and Reanimation, University of Health Sciences, Antalya Training and Research Hospital, Antalya, Türkiye.
Front Pharmacol. 2024 Jan 5;14:1326128. doi: 10.3389/fphar.2023.1326128. eCollection 2023.
In clinical practice, inadequate pain inhibition leads to increased morbidity and mortality. Increased intracellular calcium, oxidants, and proinflammatory cytokines are known to play a role in the pathogenesis of postoperative pain. Therefore, we investigated the analgesic effects of benidipine, paracetamol, and benidipine-paracetamol combination (BPC) on postoperative and normal pain thresholds in rats. Sixty-four male albino Wistar rats weighing 285-295 g were used. The without-incision rats were divided into 4 subgroups: healthy control, benidipine alone, paracetamol alone, and BPC. The scalpel-incision rats were divided into 4 subgroups: scalpel incision, scalpel incision + benidipine, scalpel incision + paracetamol, and scalpel incision + BPC. Paw pain thresholds of rats were measured using a Basile algesimeter. Biochemical analyses were performed on the paw tissues of 6 rats randomly taken from the experimental groups, each containing 8 rats. Rats were sacrificed immediately after the measurements. After the pain threshold tests were finished, the paw tissues were removed and malondialdehyde (MDA), total glutathione (tGSH), cyclooxygenase (COX), and interleukin-6 (IL-6) levels were measured. There was no significant difference between the groups in paw pain threshold and measured biochemical parameters in rats without incision. The decrease in the pain threshold of the incised paw was also best prevented by BPC, followed by benidipine and then paracetamol. Furthermore, increases in scalpel-incised paw tissue MDA, COX-2, and IL-6 levels and the decrease in tGSH were significantly suppressed by benidipine and BPC, while paracetamol could only significantly inhibit the increase in IL-6 production. The combination of the L-type Ca channel blocker benidipine and paracetamol (BPC) may provide potent analgesia. Our experimental results support that BPC may be useful in the treatment of severe pain that cannot be adequately inhibited by paracetamol.
在临床实践中，疼痛抑制不足会导致发病率和死亡率增加。已知细胞内钙、氧化剂和促炎细胞因子的增加在术后疼痛的发病机制中起作用。因此，我们研究了贝尼地平、对乙酰氨基酚以及贝尼地平 - 对乙酰氨基酚组合（BPC）对大鼠术后和正常疼痛阈值的镇痛作用。使用了64只体重在285 - 295克的雄性白化Wistar大鼠。未切开大鼠分为4个亚组：健康对照组、单独使用贝尼地平组、单独使用对乙酰氨基酚组和BPC组。手术刀切开大鼠分为4个亚组：手术刀切开组、手术刀切开 + 贝尼地平组、手术刀切开 + 对乙酰氨基酚组和手术刀切开 + BPC组。使用Basile痛觉计测量大鼠的爪部疼痛阈值。对从每个包含8只大鼠的实验组中随机选取的6只大鼠的爪部组织进行生化分析。测量后立即处死大鼠。疼痛阈值测试完成后，取出爪部组织并测量丙二醛（MDA）、总谷胱甘肽（tGSH）、环氧化酶（COX）和白细胞介素 - 6（IL - 6）水平。未切开大鼠的爪部疼痛阈值和测量的生化参数在各实验组之间无显著差异。BPC对切开爪部疼痛阈值的降低预防效果最佳，其次是贝尼地平，然后是对乙酰氨基酚。此外，贝尼地平和BPC显著抑制了手术刀切开爪部组织中MDA、COX - 2和IL - 6水平的升高以及tGSH的降低，而对乙酰氨基酚只能显著抑制IL - 6产生的增加。L型钙通道阻滞剂贝尼地平与对乙酰氨基酚的组合（BPC）可能提供强效镇痛作用。我们的实验结果支持BPC可能对治疗对乙酰氨基酚无法充分抑制的严重疼痛有用。
