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Spermidine reduced neuropathic pain in chronic constriction injury-induced peripheral neuropathy in rats |
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| Authors: | Hasan Yousefi-Manesh Samira Shirooie Tayebeh Noori Mohammad Sheibani Seyed Mohammad Tavangar Sara Hemmati Mohammad Amin Sadeghi Hassan Akbarniakhaky Zohreh Mohammadi Laleh Foroutani Ahmad Reza Dehpour |
| Affiliation: | 1. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran;2. Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran;3. Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Razi Drug Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran;4. Department of Pathology, Dr. Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran;5. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;6. School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran;7. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran |
| Abstract: | Neuropathic pain is one of the most critical types of chronic pain despite the increasing advances in medical science. Spermidine (SPD) is a natural polyamine that has wide roles in several cellular processes inducing autophagy and reducing oxidative stress. This study aimed to investigate the effects of SPD on oxidative stress markers and pain threshold in the neuropathic rat model of chronic constriction injury (CCI) model. Eighteen adult male rats were divided into three groups: sham, CCI and CCI+SPD. After induction of neuropathy via CCI model in the CCI and CCI+SPD groups, SPD (1 mg/kg/day, orally) was administered to the CCI+SPD group for 3 weeks. The behavioral tests (von Frey, hot plate) were done four times during the experiment. At the end of the study, electrophysiological tests, the H & E staining, and oxidative stress assay of the prefrontal cortex (PFC), spinal cord, and sciatic nerve were performed. The threshold of pain in hot plate and von Frey tests was significantly lower in the CCI group than in the sham group, which was reversed by SPD treatment in the CCI+ SPD group. In addition, nerve conduction was considerably lower in the CCI group than in the sham and CCI+SPD groups (P < 0.01, P < 0.05, respectively). The CCI group showed neuronal degeneration and fibrosis in the different tissues in the H & E assay; elevated tissues level of nitrite, decreased levels of superoxide dismutase (SOD), glutathione (GPx), and catalase were also observed. However, SPD treatment modulated the pathological changes and oxidative stress biomarkers. In conclusion, SPD showed beneficial effects in decreasing neuropathic pains. SPD treatment reduced oxidative stress and improved histopathological changes and behavioral tests in the CCI-induced neuropathic pain in in vivo model. |
| Keywords: | CCI neuropathic pain oxidative stress spermidine |