en Cellular and molecular Neuroscience Cellular and molecular Neuroscience Original Original <div style="text-align: justify;"><strong>Introduction</strong>: Glycogen Synthase Kinase-3&beta; (GSK-3&beta;) participates in several signaling pathways and plays a crucial role in neurodegenerative diseases, inflammation, and neuropathic pain. The ratio of phosphorylated GSK-3&beta; over total GSK-3&beta; (p-GSK-3&beta;/t-GSK-3&beta;) is reduced following nerve injury. Apoptosis is a hallmark of many neuronal dysfunctions in the context of neuropathic pain. Thus, this study aimed to evaluate the contribution of p-GSK-3&beta;/t-GSK-3&beta; ratio in spinal dorsal horn apoptosis following peripheral nerve injury.&nbsp;<br> <strong>Methods</strong>: In this study, adult male Wistar rats (220-250 g) underwent Spinal Nerve Ligation (SNL) surgery. Mechanical allodynia and thermal hyperalgesia were assessed before the surgery (day 0); then, every other day up to day 8. GSK-3&beta; selective inhibitor, AR-014418 [0.3 mg/kg, Intraperitoneal (IP)] was administrated 1 h prior to SNL on day 0, then daily up to the day 8. The GSK-3&beta; activity and apoptosis in the lumbar section (L4, L5, or L6) of the study rat&rsquo;s spinal cord were assessed by immunohistochemical and Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) staining, respectively on day 8 post-SNL.&nbsp;<br> <strong>Results</strong>: Following the SNL, the mechanical allodynia and thermal hyperalgesia increased on day 2 up to day 8 post-SNL. The ratio of p-GSK-3&beta;/t-GSK-3&beta; decreased, and the number of apoptotic cells increased in the spinal dorsal horn on day 8. However, AR-A014418 administration could increase the p-GSK-3&beta;/t-GSK-3&beta; ratio and decreased apoptosis in the SNL rats. In addition, AR-A014418 decreased the mechanical allodynia from day 4 up to day 8; however, it did not affect thermal hyperalgesia.&nbsp;<br> <strong>Conclusion</strong>: The study findings suggested that increasing the p-GSK-3&beta;/t-GSK-3&beta; ratio might be a helpful strategy for reducing the apoptotic cells and subsequent neuropathic pain during peripheral nerve injury.</div> allodynia, hyperalgesia, apoptosis, Immunohistochemistry 15 30 http://bcn.iums.ac.ir/browse.php?a_code=A-10-556-1&slc_lang=en&sid=1 Mina Rashvand mina.rashvand@yahoo.com 13700319475328460025392 13700319475328460025392 No Department of Physiology, School of Medicine, Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Samira Danyali samira.danyali@gmail.com 13700319475328460025393 13700319475328460025393 No Department of Physiology, School of Medicine, Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran.; Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Homa Manaheji manahejih@sbmu.ac.ir 13700319475328460025394 13700319475328460025394 Yes Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.