Background

Many injuries cause pain and inflammation, which are one of the major challenges for physicians. In this study, the analgesic and the anti-inflammatory effects of milnacipran were investigated on carrageenan-induced nociception and inflammation in male rats.

Methods

Pain and inflammation were induced by injection of λ-carrageenan (1% v/v) into the hind paw. Indomethacin (10 mg/kg: ip) or milnacipran (10, 20 and 40 mg/kg: ip) were administered 30 min before carrageenan. Analgesia and inflammation were measured by hot plate and plethysmometer. Finally, lipid peroxidation, tumor necrosis factor alpha (TNF-α), Interleukin 1 beta (IL-1β), Interleukin 6 (IL-6), myeloperoxidase (MPO) activity, nitric oxide (NO) and total antioxidant capacity (TAC) status evaluated in the hind paw tissue.

Results

The results showed that carrageenan caused hyperalgesia and inflammation in the hind paw tissue. Milnacipran (20 and 40 mg/kg) significantly and dose-dependently attenuated (65 ± 3.2%; p ≤0.01 and 42 ± 6.2%; p ≤ 0.001, respectively) carrageenan-induced inflammation and significantly increased (p ≤ 0.001) nociception threshold. Also, milnacipran (20 and 40 mg/kg) significantly suppressed levels of malondialdehyde (MDA), NO (p ≤ 0.05), MPO activity, TNF-α, IL-1β and IL-6 (p ≤ 0.001) following carrageenan injection. Additionally, milnacipran (10, 20 and 40 mg/kg) significantly augmented (p ≤ 0.05) TAC status following carrageenan in the hind paw tissue.

Conclusion

In the present study, milnacipran showed anti-nociceptive and anti-inflammatory effects on carrageenan-induced hyperalgesia and inflammation in a dose-dependent manner. Milnacipran reduced inflammatory edema and increased the paw withdrawal threshold probably through suppression of MDA, NO, TNF-α, IL-1β, IL-6 and MPO activity, and increase of TAC status in the hind paw tissue. Therefore, milnacipran holds important potential as an anti-inflammatory and anti-nociceptive drug. Although, further clinical trials to confirm this issue, is required.

中文翻译：

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米那普仑对发炎大鼠的抗炎和抗痛觉过敏作用：涉及髓过氧化物酶活性，细胞因子和氧化/亚硝基应激。

背景

许多伤害会导致疼痛和发炎，这是医师面临的主要挑战之一。在这项研究中，研究了米那普仑对角叉菜胶诱导的雄性大鼠伤害和炎症的镇痛作用和抗炎作用。

方法

通过将λ-角叉菜胶（1％v / v）注入后爪来诱发疼痛和炎症。在角叉菜胶前30分钟给予消炎痛（10 mg / kg：ip）或米那普仑（10、20和40 mg / kg：ip）。通过热板和体积描记仪测量镇痛和炎症。最后，脂质过氧化，肿瘤坏死因子α（TNF-α），白介素1 beta（IL-1β），白介素6（IL-6），髓过氧化物酶（MPO）活性，一氧化氮（NO）和总抗氧化能力（TAC）在后爪组织中评估状态。

结果

结果表明角叉菜胶引起后爪组织的痛觉过敏和炎症。米那普仑（20和40毫克/千克）和显著剂量依赖性地减弱（65±3.2％; p  ≤0.01和42±6.2％; p  ≤0.001）角叉菜胶诱导的炎症和显著增加（p  ≤0.001）伤害感受阈值。此外，米那普仑（20和40毫克/千克）丙二醛显著抑制水平（MDA），NO（p  ≤0.05），MPO活性，TNF-α，IL-1β和IL-6（p 角叉菜胶注射后≤0.001）。此外，米那普仑（10，20和40毫克/千克）显著增强（p  ≤0.05）TAC状态下在后爪组织角叉菜胶。

结论

在本研究中，米那普仑对角叉菜胶诱导的痛觉过敏和炎症具有剂量依赖性的抗伤害和消炎作用。Milnacipran可能通过抑制MDA，NO，TNF-α，IL-1β，IL-6和MPO活性以及增加后足组织的TAC状态，减轻了炎症性水肿并提高了足爪退缩阈值。因此，米那普仑具有作为抗炎和抗伤害感受药的重要潜力。虽然，需要进一步的临床试验来确认这个问题。