en Cellular and molecular Neuroscience Cellular and molecular Neuroscience Original Original <div style="text-align: justify;"><strong>Introduction</strong>: Genotropin, a recombinant human growth hormone (GH), has been proposed as a potential repositioning drug to treat neurological disorders. However, its efficacy in managing neuropathic pain remains unclear. This study aimed to evaluate the analgesic effects of Genotropin and investigate its potential mechanisms of action.<br> <strong>Methods</strong>: Two weeks after chronic constriction injury (CCI) of the sciatic nerve, adult male rats were randomly assigned to three main groups: Control, vehicle (normal saline [NS]), and treatment. The treatment group received Genotropin at doses of 0.3 and 0.6 mg/kg, either alone or in combination with L-arginine, L-NAME, or glutamate (n=8 per group). Pain-related behaviors were assessed using Von Frey filaments, the plantar test, and the Randall&ndash;Selitto test. Blood samples were collected to analyze oxidative and antioxidative markers.&nbsp;<br> <strong>Results</strong>: Genotropin significantly reduced mechanical allodynia (P<0.05, F=2.7) and mechanical (P<0.01, F=3.4) and thermal hyperalgesia (P<0.001, F=2.5). Pretreatment with 0.3 mg/kg GH abolished the pronociceptive effects of L-arginine (500 mg/kg) and glutamate (1000 nmol) (P<0.01; F=2, F=3) while enhancing the antinociceptive effect of L-NAME (P<0.05, F=2.8). GH also significantly reduced lipid peroxidation (P<0.01, F=3.7) and restored levels of glutathione, glutathione peroxidase (GPx), and superoxide dismutase (SOD) (P<0.01; F=11, F=10.52, F=5, respectively). Additionally, catalase (CAT) levels were significantly increased (P<0.01, F=5).<br> <strong>Conclusion</strong>: These results suggest that exogenous GH alleviates neuropathic pain and enhances antioxidant defenses in a model of peripheral neuropathic pain. The involvement of glutamate and nitric oxide (NO) pathways in GH&rsquo;s antinociceptive effects was also demonstrated. Therefore, Genotropin holds potential as a repositioned therapeutic agent for treating neuropathic pain.</div> Growth hormone (Genotropin), Neuropathic pain, Oxidative factors, Nitric oxide (NO), Glutamate 619 632 http://bcn.iums.ac.ir/browse.php?a_code=A-10-6536-1&slc_lang=en&sid=1 Sepideh Saffarpour s.saffarpour@gmail.com 13700319475328460054311 13700319475328460054311 No Department of Orthopedics, Bone and Joint Reconstruction Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Arash Mehraz arash.mehraz@gmail.com 13700319475328460054312 13700319475328460054312 No Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran. Pargol Sadeghi Tehran sadeghitehran.pargol@gmail.com 13700319475328460054313 13700319475328460054313 No Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran. Farinaz Nasirinezhad fnasirinezhad@gmail.com 13700319475328460054314 13700319475328460054314 Yes Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.