Hasanvand Amin, Ahmadizar Fariba, Abbaszadeh Abolfazl, Dehpour Ahmad-Reza, Amini-Khoei Hossein, Abbasnezhad Amir, Kharazmkia Ali
Department of Physiology and Pharmacology, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran.
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Iran J Pharm Res. 2020 Fall;19(4):67-75. doi: 10.22037/ijpr.2020.1101230.
Prevention and treatment of neuropathic pain (NP) is one of the most difficult problems in clinical practice since the underlying mechanism of NP is unclear. In previous studies, the increased production of nitric oxide (NO) has been closely linked to the induced NP. In this study, we assessed the effect of atorvastatin through NO mechanism, on inflammation, thermal hyperalgesia, thermal allodynia, and mechanical allodynia as well as sciatic nerve histological score in rat with chronic constriction injury (CCI) model. Finally, we specified the role of cytokines such as TNF-α and IL-6 in the spinal cord. Treatment with atorvastatin and L-NAME (NO inhibitor) attenuated the thermal hyperalgesia, thermal allodynia and mechanical allodynia induced by CCI. The antinociceptive consequence was better elevated with a combination of atorvastatin and L-NAME in comparison with the other groups. In addition, the treatment with these drugs also attenuated the CCI-induced TNF-α and IL-6 level in the spinal cord. Furthermore, the histological analysis showed a low level of inflammation in the sciatic nerve in the CCI rats co-treated with atorvastatin and L-NAME. Findings of our study in NP-induced CCI in the rat model demonstrate that inhibition of NO displays antinociceptive and anti-neuroinflammatory effects of atorvastatin in peripheral and central nervous system. In addition, we found that inhibition of the NO by atorvastatin could be one of the most important anti-inflammatory pathways of atorvastatin effect.
由于神经病理性疼痛（NP）的潜在机制尚不清楚，其预防和治疗是临床实践中最困难的问题之一。在先前的研究中，一氧化氮（NO）生成增加与诱导的NP密切相关。在本研究中，我们通过NO机制评估阿托伐他汀对慢性压迫性损伤（CCI）模型大鼠的炎症、热痛觉过敏、热感觉异常和机械性感觉异常以及坐骨神经组织学评分方面的影响。最后，我们明确了细胞因子如肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）在脊髓中的作用。阿托伐他汀和L-NAME（NO抑制剂）治疗减轻了CCI诱导的热痛觉过敏、热感觉异常和机械性感觉异常。与其他组相比，阿托伐他汀和L-NAME联合使用时抗伤害感受效果更好。此外，这些药物治疗还减轻了CCI诱导的脊髓中TNF-α和IL-6水平。此外，组织学分析显示，阿托伐他汀和L-NAME联合治疗的CCI大鼠坐骨神经炎症水平较低。我们在大鼠模型NP诱导的CCI中的研究结果表明，抑制NO可显示阿托伐他汀在周围和中枢神经系统中的抗伤害感受和抗神经炎症作用。此外，我们发现阿托伐他汀抑制NO可能是阿托伐他汀发挥作用的最重要抗炎途径之一。
