• Yu Song, Zhi-Yong Wang, Jun Luo, Wen-Can Han, Xiao-Yi Wang, Cui Yin, Wei-Nan Zhao, Su-Wan Hu, Qi Zhang, Yan-Qiang Li, and Jun-Li Cao.
• Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu Province 221004, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu Province 221004, China; Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province 221002, China.
• Neuroscience. 2023 Dec 15; 535: 506250-62.

AbstractIncreasing evidence suggests that alternative splicing plays a critical role in pain, but its underlying mechanism remains elusive. Herein, we employed complete Freund's adjuvant (CFA) to induce inflammatory pain in mice. A combination of genomics research techniques, lentivirus-based genetic manipulations, behavioral tests, and molecular biological technologies confirmed that splicing factor Cwc22 mRNA and CWC22 protein were elevated in the spinal dorsal horn at 3 days after CFA injection. Knockdown of spinal CWC22 by lentivirus transfection (lenti-shCwc22) reversed CFA-induced thermal hyperalgesia and mechanical allodynia, whereas upregulation of spinal CWC22 (lenti-Cwc22) in naïve mice precipitated pain. Comprehensive transcriptome and genome analysis identified the secreted phosphoprotein 1 (Spp1) as a potential gene of CWC22-mediated alternative splicing, however, only Spp1 splicing variant 4 (Spp1 V4) was involved in thermal and mechanical nociceptive regulation. In conclusion, our findings demonstrate that spinal CWC22 regulates Spp1 V4 to participate in CFA-induced inflammatory pain. Blocking CWC22 or CWC22-mediated alternative splicing may provide a novel therapeutic target for the treatment of persistent inflammatory pain.Copyright © 2023 IBRO. Published by Elsevier Ltd. All rights reserved.

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