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other·preclinical research, neurology, biomedical research, antioxidants·PMC10556381

Quercetin Ameliorates Neuropathic Pain after Brachial Plexus Avulsion via Suppressing Oxidative Damage through Inhibition of PKC/MAPK/NOX Pathway

Current Neuropharmacology · 6 authors, 6 centres

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TL;DR

The study established a rat model of neuropathic pain by avulsing the right C7 ventral and dorsal roots.

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The study established a rat model of neuropathic pain by avulsing the right C7 ventral and dorsal roots. The researchers assessed pain behavior using mechanical allodynia tests and evaluated neuroinflammation and oxidative stress through biochemical assays and immunohistochemistry. The central result was that QCN treatment significantly attenuated mechanical allodynia, elevated levels of antioxidant enzymes (CAT, SOD, GPx, TAC) in the spinal dorsal horn, and inhibited the activation of macrophages, microglia, astrocytes, and P2X receptors. In vitro experiments on H2O2-stimulated BV-2 cells confirmed that QCN reduced ROS production and inhibited PKC/NOX pathway activation.

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other

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preclinical research

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ORIGINAL PAPER

PMC10556381

Quercetin Ameliorates Neuropathic Pain after Brachial Plexus Avulsion via Suppressing Oxidative Damage through Inhibition of PKC/MAPK/NOX Pathway

Current Neuropharmacology

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ABSTRACT

Abstract Background Brachial plexus avulsion (BPA) animally involves the separation of spinal nerve roots themselves and the correlative spinal cord segment, leading to formidable neuropathic pain of the upper limb. Methods The right seventh cervical (C7) ventral and dorsal roots were avulsed to establish a neuropathic pain model in rats. After operation, rats were treated with quercetin (QCN) by intragastric administration for 1 week. The effects of QCN were evaluated using mechanical allodynia tests and biochemical assay kits. Results QCN treatment significantly attenuated the avulsion-provoked mechanical allodynia, elevated the levels of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) and total antioxidant capacity (TAC) in the C7 spinal dorsal horn. In addition, QCN administration inhibited the activations of macrophages, microglia and astrocytes in the C6 dorsal root ganglion (DRG) and C6-8 spinal dorsal horn, as well as attenuated the release of purinergic 2X (P2X) receptors in C6 DRG. The molecular mechanism underlying the above alterations was found to be related to the suppression of the PKC/MAPK/NOX signal pathway. To further study the anti-oxidative effects of QCN, we applied QCN on the H 2 O 2 -induced BV-2 cells in vitro , and the results attested that QCN significantly ameliorated the H 2 O 2 -induced ROS production in BV-2 cells, inhibited the H 2 O 2 -induced activation of PKC/MAPK/NOX pathway. Conclusion Our study for the first time provided evidence that QCN was able to attenuate pain hypersensitivity following the C7 spinal root avulsion in rats, and the molecular mechanisms involve the reduction of both neuro-inflammatory infiltration and oxidative stress via suppression of P2X receptors and inhibition of the activation of PKC/MAPK/NOX pathway. The results indicate that QCN is a natural compound with great promise worthy of further development into a novel therapeutic method for the treatment of BPA-induced neuropathic pain. Keywords: Brachial plexus avulsion, neuropathic pain, quercetin, neuro-inflammatory infiltration, oxidative damage, PKC/MAPK/NOX pathway

CITATION EXPORT

Yanfeng Huang, Xie Zhang, Yidan Zou et al.. Quercetin Ameliorates Neuropathic Pain after Brachial Plexus Avulsion via Suppressing Oxidative Damage through Inhibition of PKC/MAPK/NOX Pathway. Current Neuropharmacology. (2023). https://doi.org/10.2174/1570159X21666230802144940

AUTHORS

6 · 6 CENTRES

Yanfeng Huang, Xie Zhang, Yidan Zou, Qiuju Yuan, Yan-Fang Xian, Zhi-Xiu Lin

1School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China;
2Research Center for Integrative Medicine of Guangzhou University of Chinese Medicine, Key Laboratory of Chinese Medicine Pathogenesis and Therapy Research, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong. P.R. China;
3Department of Medical Biotechnology, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong. P.R. China;
4Department of Anaesthesia and Intensive Care and Peter Hung Pain Research Institute, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China;
5Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong Science Park, Shatin, N.T., Hong Kong SAR, China;
6Hong Kong Institute of Integrative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China