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Synergistic effect of ellagic acid and gabapentin in a rat model of neuropathic pain

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Abstract

Background: Neuropathic pain is a subtype of chronic pain characterized by a primary lesion or dysfunction of the peripheral or central nervous system. The current pain management of neuropathic pain is inadequate and needs new medications. Aim: We studied the effects of 14 days of intraperitoneal ellagic acid (EA) and gabapentin administration in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the right sciatic nerve. Methods: Rats were divided into six groups: (1) control, (2) CCI, (3) CCI + EA (50 mg/kg), 4) CCI + EA (100 mg/kg), 5) CCI + gabapentin (100 mg/kg), and 6) CCI + EA (100 mg/kg) + gabapentin (100 mg/kg). Behavioral tests, including mechanical allodynia, cold allodynia, and thermal hyperalgesia, were conducted on days − 1(pre-operation), 7, and 14 post-CCI. In addition, at day 14 post-CCI, spinal cord segments were collected to measure the expression of inflammatory markers, including tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), and oxidative stress markers, including malondialdehyde (MDA) and thiol. Results: CCI increased mechanical allodynia, cold allodynia, and thermal hyperalgesia in rats which were reduced by treatment with EA (50 or 100 mg/kg), gabapentin, or their combination. CCI increased TNF-α, NO, and MDA levels and decreased thiol content in the spinal cord, which all were reverted by administration of EA (50 or 100 mg/kg), gabapentin, or their combination. Conclusion: This is the first report on ellagic acid’s ameliorative effect in rats’ CCI-induced neuropathic pain. This effect can be attributed to its anti-oxidative and anti-inflammatory, thus making it potentially useful as an adjuvant to conventional treatment.

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Data Availability

The datasets used for analysis in this study are available upon request from the corresponding author.

Code Availability

Not applicable.

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Acknowledgements

This paper is based on the results from the thesis of two Medical Doctorate candidates. Two separate research grants supported this study (IDs: 992112 and 4000244). The Vice-Chancellor for Research and Technology, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran, provided the grants.

Funding

Two separate research grants supported this study (IDs: 992112 and 4000244). The Vice-Chancellor for Research and Technology, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran, provided the grants.

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Authors and Affiliations

  1. Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Fatemeh Forouzanfar, Ali Mohammad Pourbagher-Shahri, Saeide mahdianpour, Mahdiyeh Esmaeili & Hamed Ghazavi

  2. Department of Neuroscience, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Fatemeh Forouzanfar & Hamed Ghazavi

  3. Medical Toxicology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Nima Khalili Tanha

Authors
  1. Fatemeh Forouzanfar
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  2. Nima Khalili Tanha
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  3. Ali Mohammad Pourbagher-Shahri
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  4. Saeide mahdianpour
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  5. Mahdiyeh Esmaeili
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  6. Hamed Ghazavi
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Contributions

Fatemeh Forouzanfar and Hamed Ghazavi designed the experiment. Fatemeh Forouzanfar, Hamed Ghazavi, Nima Khalili Tanha, Ali Mohammad Pourbagher-Shahri, Saeide mahdianpour, and Mahdiyeh Esmaeili did the experiments. Fatemeh Forouzanfar, Ali Mohammad Pourbagher-Shahri, and Hamed Ghazavi wrote the paper. Fatemeh Forouzanfar and Hamed Ghazavi prepared the final draft of the paper.

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Correspondence to Hamed Ghazavi.

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The authors have no conflicts of interest to disclose in this study.

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The Ethical Committee of MUMS approved the study (992112; ethics approval code: IR.MUMS.MEDICAL.REC.1400.103, 4000244; IR.MUMS.MEDICAL.REC.1400.410).

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Forouzanfar, F., Tanha, N.K., Pourbagher-Shahri, A.M. et al. Synergistic effect of ellagic acid and gabapentin in a rat model of neuropathic pain. Metab Brain Dis 38, 1421–1432 (2023). https://doi.org/10.1007/s11011-023-01190-x

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