Evaluating the impact of amitriptyline on Nitric Oxide signaling in rat models of neuropathic pain

Mohammadi, Hamid Reza and Haghighatian, Zahra and Beiranvand, Behrouz and Amanolahi Baharvand, Peyman and Hasanvand, Amin (2025) Evaluating the impact of amitriptyline on Nitric Oxide signaling in rat models of neuropathic pain. Immunopharmacol Immunotoxicol.

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Abstract

Introduction: Nitric oxide (NO) plays a crucial role in the induction of neuropathic pain by stimulating the production of inflammatory cytokines. Additionally, research indicates that amitriptyline can inhibit nitric oxide production. In this study, we examined the inhibitory role of the nitric oxide signaling pathway through the administration of amitriptyline in the treatment of neuropathic pain. Methods: Forty rats were randomly assigned to five groups, with eight animals in each group: (1) Sham-operated, (2) Chronic constriction injury (CCI), (3) CCI plus amitriptyline, (4) CCI plus amitriptyline and L-arginine, and (5) CCI plus amitriptyline and L-NAME. Behavioral tests, including thermal hyperalgesia, cold allodynia, and mechanical allodynia, were conducted on the fourth, seventh, and fourteenth days following CCI induction. On the final day, spinal cord samples were collected to assess the levels of inflammatory cytokines. Additionally, the sciatic nerve was isolated on the same day for histological examination. Results: The results indicated that the administration of amitriptyline can reduce levels of inflammatory cytokines and improve symptoms of neuropathic pain. It should be noted that the simultaneous use of L-NAME and amitriptyline increases the therapeutic impacts of amitriptyline. However, the beneficial effects of amitriptyline are reduced by the nitric oxide stimulation induced by L-arginine. Conclusion: It was determined that one of the mechanisms by which amitriptyline ameliorates neuropathic pain is the inhibition of the nitric oxide signaling pathway. In this study, this effect was associated with a reduction in the release of inflammatory cytokines and a decrease in inflammation surrounding the nerve

Item Type: Article
Subjects: R Medicine > RZ Other systems of medicine
Divisions: Faculty of Medicine, Health and Life Sciences > School of Medicine
Depositing User: lorestan university
Date Deposited: 29 Jun 2025 07:28
Last Modified: 29 Jun 2025 07:28
URI: http://eprints.lums.ac.ir/id/eprint/5129

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