Abstract
The current pharmacotherapy of neuropathic pain is inadequate as neuropathic pain involves varied clinical manifestations with multifactorial etiology, modulated by a cascade of physical and molecular events leading to different clinical presentations of pain. There is an accumulating evidence of the involvement of oxidative stress in neuropathy, and antioxidants have shown promise in mitigating neuropathic pain syndromes. To explore the evidence supporting this beneficial proclivity of antioxidants, this study investigated the antinociceptive effectiveness of N-(2-mercaptopropionyl)glycine or tiopronin, a well-recognized aminothiol antioxidant, in a refined chronic constriction injury (CCI) rat model of neuropathic pain. Tiopronin (10, 30, and 90 mg/kg, i.p.) and pregabalin (30 mg/kg, i.p.) were administered daily after CCI surgery. The neuropathic paradigms of mechanical/cold allodynia and mechanical/heat hyperalgesia were assessed on days 3, 7, 14, and 21 post-nerve ligation. At the end of study, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were estimated in the sciatic nerve, dorsal root ganglion, and spinal cord for assessing the extent of oxidative stress. The expression of neuropathic nociception was attenuated by tiopronin which was observed as a significant attenuation of CCI-induced allodynia and hyperalgesia. Tiopronin reversed the neuronal oxidative stress by significantly reducing MDA, and increasing SOD, CAT, and GSH levels. Pregabalin also showed similar beneficial propensity on CCI-induced neuropathic aberrations. These findings suggest prospective neuropathic pain attenuating efficacy of tiopronin and further corroborated the notion that antioxidants are effective in mitigating the development and expression of neuropathic pain and underlying neuronal oxidative stress.
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Data availability
The authors declare that the data supporting the findings of this study are available within the article (and its supplementary information file).
Change history
07 December 2020
A Correction to this paper has been published: https://doi.org/10.1007/s00210-020-02033-7
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Acknowledgments
We are thankful to Wilshire Laboratories (Pvt.) Ltd., Lahore, Pakistan, for the supply of pregabalin active material.
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Tiopronin (PubChem CID: 5483), Pregabalin (PubChem CID: 5486971).
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FS as research supervisor guided the research group in planning and conducting experiments throughout the study duration. MS, NA, and UF performed the experiments, interpreted the data, and carried out necessary statistical analysis. SAb, SAk, IU, NR, and ZUD provided inputs on the research work at different stages. MS prepared the initial draft of the manuscript. NUI critically revised the manuscript for important intellectual content. All authors read and approved the manuscript and all data were generated in-house and that no paper mill was used.
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The experimental procedures on animals were performed in accordance with the UK Animals (Scientific Procedures) Act 1986 and were approved by the Ethical Committee of the Department of Pharmacy, University of Peshawar (Reference No. 13/EC-15/Pharm). Moreover, these experimental protocols also conformed to the guidelines of Animal Research: Reporting In Vivo experiments (ARRIVE) and International Association for the Study of Pain (IASP).
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Shahid, M., Subhan, F., Islam, N.U. et al. The antioxidant N-(2-mercaptopropionyl)-glycine (tiopronin) attenuates expression of neuropathic allodynia and hyperalgesia. Naunyn-Schmiedeberg's Arch Pharmacol 394, 603–617 (2021). https://doi.org/10.1007/s00210-020-01995-y
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DOI: https://doi.org/10.1007/s00210-020-01995-y