Hashemi Boshra, Fakhri Sajad, Kiani Amir, Abbaszadeh Fatemeh, Miraghaee Shahram, Mohammadi Mohammad, Echeverría Javier
Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Front Pharmacol. 2024 Nov 25;15:1467788. doi: 10.3389/fphar.2024.1467788. eCollection 2024.
Neuropathic pain is a debilitating neurological disorder and is on the rise. Since no effective treatment has been so far approved to combat the complex pathological mechanisms behind neuropathic pain, finding new therapeutic candidates is of great importance. Astaxanthin (AST) is a carotenoid with strong antioxidant, and anti-inflammatory activities.
The present research aimed to evaluate the ameliorative effects of AST on a rat model of neuropathic pain.
To induce neuropathic pain, a chronic constriction injury (CCI) model was employed. Accordingly, Wistar rats were divided into nine groups of six including sham, negative control group (CCI), positive control group gabapentin (100 mg/kg), AST (5, 10 mg/kg), flumazenil (0.5 mg/kg), naloxone (0.1 mg/kg), AST (10 mg/kg) + flumazenil (0.5 mg/kg), and AST (10 mg/kg) + naloxone (0.1 mg/kg) were administered intraperitoneally on days 1, 3, 5, 7, 10, and 14. To check the experimental signs of neuropathic pain and motor dysfunction, hot plate, acetone drop, and open field tests were used at the same time points. Additionally, biochemical assay and zymography were done on days 7 and 14 to assess the changes in catalase, glutathione and nitrite, as well as matrix metalloproteinases (MMP-2 and MMP-9). Besides, histological evaluations were performed for tissue damages on days 7 and 14.
Results indicated that intraperitoneal injection of AST improved allodynia, hyperalgesia, and locomotor activity after CCI. AST also increased catalase and glutathione while suppressing nitrite, MMP-2, and MMP-9 activity through opioid/benzodiazepine receptors.
The results highlighted AST as a promising candidate against neuropathic pain with beneficial effects on motor function by suppressing inflammatory mediators, and augmenting antioxidant factors, passing through opioid/benzodiazepine receptors.
神经性疼痛是一种使人衰弱的神经系统疾病，且呈上升趋势。由于目前尚无有效的治疗方法被批准用于对抗神经性疼痛背后复杂的病理机制，寻找新的治疗候选药物至关重要。虾青素（AST）是一种具有强大抗氧化和抗炎活性的类胡萝卜素。
本研究旨在评估虾青素对神经性疼痛大鼠模型的改善作用。
为诱导神经性疼痛，采用慢性缩窄损伤（CCI）模型。相应地，将Wistar大鼠分为九组，每组六只，包括假手术组、阴性对照组（CCI）、阳性对照组加巴喷丁（100mg/kg）、虾青素（5、10mg/kg）、氟马西尼（0.5mg/kg）、纳洛酮（0.1mg/kg）、虾青素（10mg/kg）+氟马西尼（0.5mg/kg）以及虾青素（10mg/kg）+纳洛酮（0.1mg/kg），于第1、3、5、7、10和14天腹腔注射给药。在相同时间点使用热板法、丙酮滴注法和旷场试验来检查神经性疼痛和运动功能障碍的实验体征。此外，在第7天和第14天进行生化分析和酶谱分析，以评估过氧化氢酶、谷胱甘肽和亚硝酸盐以及基质金属蛋白酶（MMP - 2和MMP - 9）的变化。此外，在第7天和第14天对组织损伤进行组织学评估。
结果表明，腹腔注射虾青素可改善CCI后的痛觉过敏、痛觉超敏和运动活动。虾青素还通过阿片类/苯二氮䓬受体增加过氧化氢酶和谷胱甘肽，同时抑制亚硝酸盐、MMP - 2和MMP - 9的活性。
结果突出了虾青素作为一种有前景的抗神经性疼痛候选药物，通过抑制炎症介质和增强抗氧化因子，经阿片类/苯二氮䓬受体发挥作用，对运动功能具有有益影响。
