Neuroprotective and Anti-inflammatory Role of Atorvastatin and Its Interaction with Nitric Oxide (NO) in Chronic Constriction Injury-induced Neuropathic Pain

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.