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 problemsin clinical practice since the underlying mechanism of NP is unclear. In previous studies, theincreased production of nitric oxide (NO) has been closely linked to the induced NP. In thisstudy, we assessed the effect of atorvastatin through NO mechanism, on inflammation, thermalhyperalgesia, thermal allodynia, and mechanical allodynia as well as sciatic nerve histologicalscore in rat with chronic constriction injury (CCI) model. Finally, we specified the role ofcytokines 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 allodyniainduced by CCI. The antinociceptive consequence was better elevated with a combination ofatorvastatin and L-NAME in comparison with the other groups. In addition, the treatment withthese 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 cotreatedwith atorvastatin and L-NAME. Findings of our study in NP-induced CCI in the rat modeldemonstrate that inhibition of NO displays antinociceptive and anti-neuroinflammatory effectsof atorvastatin in peripheral and central nervous system. In addition, we found that inhibitionof the NO by atorvastatin could be one of the most important anti-inflammatory pathways ofatorvastatin effect.