Spermidine reduced neuropathic pain in chronic constriction injury‐induced peripheral neuropathy in rats

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.

Nutritional Factors: Benefits in Glaucoma and Ophthalmologic Pathologies

“…The role of spermidine has been highlighted in the preservation of mitochondrial function, protein deacetylation, and anti-inflammation [ 63 ]. Yousefi-Manesh et al demonstrated that spermidine reduced neuropathic pain in injury-induced neuropathy in a murine model [ 64 ]. Spermidine has also been shown to help maintain hormonal balance and generally reduce oxidative stress [ 64 ].…”

“…Yousefi-Manesh et al demonstrated that spermidine reduced neuropathic pain in injury-induced neuropathy in a murine model [ 64 ]. Spermidine has also been shown to help maintain hormonal balance and generally reduce oxidative stress [ 64 ].…”

Evaluating the anti-neuropathic effects of naringin-loaded chitosan nanocarriers in a murine model of constriction injury

“…Nitrite has been shown to play a complex role in neuropathy pain and is implicated in hyperalgesia effects as well as neuroinflammation through its interaction with oxidative stress. 57,58 The analysis of nitrite levels in the serum revealed a significant increase in neuropathic rats with CCI-induced injury compared to the sham group (Figure 6(b)). Whereas, administration of GBP produced a steep reduction in the level of nitrite relative to the CCI group (p < 0.001).…”

Novel Drug Targets and Emerging Pharmacotherapies in Neuropathic Pain

“…It was previously shown to exert analgesic effects by targeting various pathways involved in neuropathic pain, including the activation of cannabinoid receptors and the inhibition of inflammatory mediators [ 197 ]. Spermidine is a naturally occurring polyamine that plays essential roles in various cellular processes, including cell growth, differentiation, and neuronal function [ 198 ]. Studies indicate that spermidine may alleviate pain hypersensitivity, modulate neurotransmitter systems, and promote neuroprotection [ 198 ].…”

“…Spermidine is a naturally occurring polyamine that plays essential roles in various cellular processes, including cell growth, differentiation, and neuronal function [ 198 ]. Studies indicate that spermidine may alleviate pain hypersensitivity, modulate neurotransmitter systems, and promote neuroprotection [ 198 ]. With its favorable safety profile, spermidine supplementation could offer a viable option for managing neuropathic pain, although further research is needed to determine its mechanisms of action and optimal usage in human subjects [ 198 ].…”