TDZD-8 alleviates oxaliplatin induced neuropathic pain

He-yu Yang; Zhuo-qi Cao; Mei-rong XU; Jun Zhang; Ling Liu; Yu-jia Wang

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TDZD-8 alleviates oxaliplatin induced neuropathic pain

Author: He-Yu YANG ¹ ; Zhuo-Qi CAO ¹ ; Mei-Rong XU ¹ ; Jun ZHANG ¹ ; Ling LIU ¹ ; Yu-Jia WANG ²
Author Information

1. School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology
2. The First Affiliated Hospital of Hubei University of Science and Technology, Xianning Central Hospital
Publication Type:Journal Article
Keywords: GSK-3β; microglia; neuropathic pain; NLRP3 inflammasome; spinal inflammation; TDZD-8
From: Chinese Pharmacological Bulletin 2023;39(4):679-684
CountryChina
Language:Chinese
Abstract: Aim To explore the effect of GSK-3β (glycogen synthase kinase-3 beta) inhibitor TDZD-8 on the neuropathic pain induced by side effects of chemotherapeutic drug oxaliplatin and the underlying mechanism. Methods The rat model of oxaliplatin-induced neuropathic pain was established by intraperitoneal injection of oxaliplatin for five consecutive days; the anti-nociception effect was detected by intrathecal injection of TDZD-8. The spontaneous flinches and mechanical pain threshold were used to detect the changes of pain behavior of rats; immunofluorescence and Western blot analysis were used to detect the changes of spinal inflammation and protein levels of rats. Results Intrathecally injection of TDZD-8 significantly alleviated oxaliplatin induced hyperalgesia in rats. TDZD-8 injection obviously inhibited the activation spinal microglia and the inflammatory reaction. TDZD-8 administration significantly inhibited GSK-3β activation. Conclusion TDZD-8 blocks GSK-3β activation, decreases NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome mediated spinal inflammation and alleviates neuropathic pain.