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image of Ameliorative Potential of Ethyl Gallate in a Rat Model of Chronic Constriction Injury-Induced Neuropathic Pain

Abstract

Introduction

Neuropathic pain (NP), a chronic and debilitating condition resulting from nerve injury, remains a significant clinical challenge due to limited effective therapies. Ethyl gallate (EG), a natural ester of gallic acid, possesses potent antioxidant and anti-inflammatory properties; however, its role in NP management has not been previously explored.

Methods

This study investigated the neuroprotective potential of EG in a chronic constriction injury (CCI)-induced NP model in rats. EG was administered intraperitoneally at doses of 10, 15, and 20 mg/kg/day for 14 days. Behavioral assessments, including thermal hyperalgesia, mechanical allodynia, and motor nerve conduction velocity (MNCV), were performed. Biochemical evaluations, such as oxidative stress markers (SOD, GSH, catalase, MDA) and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) were conducted. Histopathological analysis of the sciatic nerve was performed to assess structural integrity. Additionally, molecular docking was employed to evaluate the binding interactions of EG with key redox and inflammatory regulators, Nrf2 and NF-κB, in comparison with the standard drug gabapentin (GBP).

Results

EG significantly alleviated CCI-induced pain behaviors, demonstrated by increased paw withdrawal latency, enhanced mechanical threshold, and improved MNCV. EG treatment restored antioxidant enzyme activities and reduced MDA levels, indicating decreased oxidative stress. Additionally, EG markedly lowered pro-inflammatory cytokine levels. Histological findings revealed preserved nerve fiber integrity and reduced structural damage in EG-treated groups. Molecular docking revealed stronger binding affinity of EG (–6.8 kcal/mol with Nrf2; -5.1 kcal/mol with NF-κB) compared to GBP (–5.9 kcal/mol and –4.3 kcal/mol, respectively), supporting its potential mechanistic role in modulating oxidative stress and inflammatory pathways.

Discussion

These results suggest that EG mitigates NP symptoms by modulating oxidative stress and inflammation. Its ability to enhance endogenous antioxidant defenses and suppress pro-inflammatory responses underlies its neuroprotective action.

Conclusion

EG demonstrates promising therapeutic potential in the management of NP through its antioxidant, anti-inflammatory, and neuroprotective properties. Further molecular studies are warranted to elucidate its underlying mechanisms.

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2026-01-19
2026-01-25

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/content/journals/cnr/10.2174/0115672026409563251204065841
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Ameliorative Potential of Ethyl Gallate in a Rat Model of Chronic Constriction Injury-Induced Neuropathic Pain
Bentham Science Publishers ; https://doi.org/10.2174/0115672026409563251204065841
/content/journals/cnr/10.2174/0115672026409563251204065841
/content/journals/cnr/10.2174/0115672026409563251204065841
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  • Article Type:     Research Article
Keywords: nuclear factor erythroid 2-related factor 2 ; neuropathic pain ; neuroinflammation ; nuclear factor kappa-light-chain-enhancer of activated B cells ; chronic constriction injury ; Ethyl gallate ; oxidative stress

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