Saffarpour S, Mehraz A, Sadeghi Tehran P, Nasirinezhad F. Impact of Genotropin on Oxidative Stress, Glutamate, and Nitric Oxide Pathways in a Rat Model of Peripheral Neuropathy. BCN 2025; 16 (3) :619-632
URL:
http://bcn.iums.ac.ir/article-1-2913-en.html
1- Department of Orthopedics, Bone and Joint Reconstruction Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
2- Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran.
3- Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran.
4- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran. & Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. & Center for Experimental and Comparative Study, Iran University of Medical Sciences, Tehran, Iran.
Abstract:
Introduction: 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.
Methods: 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–Selitto test. Blood samples were collected to analyze oxidative and antioxidative markers.
Results: 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).
Conclusion: 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’s antinociceptive effects was also demonstrated. Therefore, Genotropin holds potential as a repositioned therapeutic agent for treating neuropathic pain.
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● The Genotropin at a non-toxic dose may improve pain-related behavior in male rats with peripheral neuropathy.
● The Genotropin may enhance oxidative factors in male rats with peripheral neuropathic pain.
● The glutamate and nitric oxide pathways are involved in the analgesic effect of Genotropin.
Plain Language Summary
Neuropathic pain, caused by nerve damage, is a chronic condition that can be difficult to treat with existing medications. Genotropin, a laboratory-made form of human growth hormone (GH), is commonly used for growth-related disorders but is now being studied for new uses, including treating nerve-related pain. This study explored whether Genotropin can reduce neuropathic pain in male rats and aimed to understand how it works in the body. We induced nerve injury in rats to simulate peripheral neuropathic pain. Two weeks after the injury, the rats were divided into different groups, including a control group (untreated), a group treated with placebo (saline), two groups treated with Genotropin at two different doses, and five groups received Genotropin in combination with other substances at different doses (L-arginine, L-NAME, or glutamate) to examine the role of specific biological pathways. We measured how the rats responded to different pain tests and analyzed blood samples to assess levels of oxidative stress. The results showed that Genotropin reduced pain-related behaviors and increased the body’s antioxidant defenses. Additionally, the findings suggest that Genotropin’s pain-relieving effects involve the glutamate and nitric oxide (NO) pathways—two important chemical systems in the nervous system. In conclusion, Genotropin may help alleviate neuropathic pain and enhance antioxidant balance, making it a promising candidate for repurposing as a treatment for nerve pain. Further studies are needed to confirm these effects and evaluate safety in humans.
Type of Study:
Original |
Subject:
Cellular and molecular Neuroscience Received: 2024/04/6 | Accepted: 2024/12/4 | Published: 2025/05/29