Drug Design, Development and Therapy (Jul 2024)
Morin Regulates M1/M2 Microglial Polarization via NF-κB p65 to Alleviate Vincristine-Induced Neuropathic Pain
Abstract
Yi Shao,* Yunfu Chen,* Xin Lan, Jun Lu, Guangling Tang, Sijie Tang, Ruixue Zhai, Chao Chen, Xinglong Xiong, Jing Shi Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Shi, Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, No. 28 Beijing Road, Guiyi Street, Yunyan District, Guiyang, Guizhou, 550001, People’s Republic of China, Tel +86-18685034016, Email [email protected]: Morin can alleviate vincristine-induced neuropathic pain via inhibiting neuroinflammation. Microglial cells play an important role in initiating and maintenance of pain and neuroinflammation. It remains unclear whether morin exerts antinociceptive properties through the regulation of microglial cells. This study aimed to elucidate the mechanisms of morin against neuropathic pain focusing on microglial cells.Methods: The thermal withdrawal latency and mechanical withdrawal threshold were used as measures of pain behaviours. Histological abnormalities of the sciatic nerve were observed with transmission electron microscopy. The sciatic functional index and the sciatic nerve conduction velocity were used as measures of the functional deficits of the sciatic nerve. Inflammatory factors were detected using ELISA. The expression of M1/M2 polarization markers of microglia and nuclear factor κB (NF-κB) p65 were measured by immunofluorescence, real-time quantitative PCR and Western blotting.Results: Morin alleviated vincristine-induced abnormal pain, sciatic nerve injury, and neuroinflammatory response in rats. Furthermore, morin decreased the expression of NF-κB P65 and M1 activation markers, increased the expression of M2 activation markers. Additionally, phorbol 12-myristate 13-acetate reversed the effects of morin on microglial polarization, the production of inflammatory factors and neuropathic pain, while ammonium pyrrolidine dithiocarbamate showed the opposite effects.Conclusion: Our results demonstrate that morin inhibits neuroinflammation to alleviate vincristine-induced neuropathic pain via inhibiting the NF-κB signalling pathway to regulate M1/M2 microglial polarization.Keywords: neuropathic pain, morin, microglia, NF-κB, neuroinflammation
