The Antinociceptive Effects of Combined Treatment With Atorvastatin and Vitamin C in the Chronic Constriction Injury Model of Rats.

Abstract

Introduction: Neuropathic pain (NP) is caused by damage to the somatosensory system. Nerve damage often results in chronic pain states, including hyperalgesia and allodynia. This study aims to evaluate the anti-nociceptive effects of atorvastatin, vitamin C, and their combination on various laboratory tests in an experimental model NP in rats.

Methods: To assess the analgesic effects of atorvastatin (5 and 10 mg/kg), vitamin C (500 mg/kg), and their co-administration on chronic constriction injury (CCI) was induced in rats. Behavioral tests, motor nerve conduction velocity (MNCV), pro-inflammatory cytokines, and oxidative markers were measured. Furthermore, histopathological examination was performed.

Results: In the present study, it was found that the CCI model can significantly cause hyperalgesia and allodynia on the 21^st postoperative day. It was found that the co-administration of vitamin C and atorvastatin has attenuating effects on allodynia and hyperalgesia. Co-administration of vitamin C and atorvastatin also improved MNCV. In the treatment groups, the inflammatory reactions and oxidative markers decreased. Moreover, the co-administration of atorvastatin and vitamin C decreased the perineural inflammation around the sciatic nerve.

Conclusion: The results of this study showed that vitamin C potentiates the analgesic effects of atorvastatin in this model of experimental pain, and simultaneous consumption of these medications may be considered as effective therapeutics for NP. The protective properties of atorvastatin, and vitamin C, and their combination on the NP that were assessed can be regarded as a novelty for this study.

Highlights: The co-administration of atorvastatin and vitamin C significantly decreases inflammatory cytokines.The co-administration of atorvastatin and vitamin C significantly decreases stress oxidant markers.The co-administration of atorvastatin and vitamin C significantly attenuated nociceptive effects.

Plain language summary: Nerve damage causes the deposition of inflammatory factors and or oxidative stress at the site of injury, which in turn activates glial cells that are involved in increasing the inflammatory process by producing and releasing pro-inflammatory agents and oxidative stress. Among statins, atorvastatin is a drug to reduce inflammation, and its effectiveness has been recorded as an antioxidant effect. Vitamin C is known as a neuroprotective agent. Ascorbate inhibits the production of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in monocytes in high doses (20 mM) by inhibiting them. The rats were randomly divided into 7 groups of 10 animals as follows: 1: Sham-operated, 2: Chronic constriction injury (CCI), 3: CCI+vitamin C (500 mg/kg), 4: CCI+atorvastatin (5 mg/kg), 5: CCI+atorvastatin (10 mg/kg), 6: CCI+vitamin C (500 mg/kg)+atorvastatin (5 mg/kg), and 7: CCI+vitamin C (500 mg/kg)+atorvastatin (10 mg/kg). The results of the present study indicated that the anti-inflammatory, antioxidant, and neuroprotective properties of vitamin C and atorvastatin improved the effects of CCI in an empirical neuropathic in rats. Moreover, it was shown that the associated treatment with vitamin C and atorvastatin can reduce inflammatory factors, such as TNF-α and IL-6, and oxidative markers, such as glutathione peroxidase (GPx), superoxide dismutase (SOD), and malonaldehyde (MDA), while the nerve conduction velocity enhanced and inflammation decreased in histology studies in CCI rats.