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

Document Type : Research article


1 Department of Physiology and Pharmacology, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran.

2 Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.

3 Department of Plastic and Reconstructive Surgery, Hazrat Fatemeh Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

4 Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

5 Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.

6 Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

7 Nutritional Health Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran.

8 Department of Clinical Pharmacy, Faculty of Pharmacy, Lorestan University of Medical Sciences, Khorramabad, Iran


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 cotreated
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.

Graphical Abstract

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


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