Academy of Medical Sciences of I.R. Iran Archives of Iranian Medicine 1029-2977 27 8 2024 08 01 Potentiation of Imipramine-Induced Anti-hyperalgesic and Anti-Nociceptive Effects by Citicoline in the Sciatic Nerve Ligated Mice 456 464 10.34172/aim.28772 EN Negar Raissi-Dehkordi https://orcid.org/0000-0002-6103-9449 Nastaran Raissi-Dehkordi Bardia Hajikarimloo Fatemeh Khakpai Moammad-Reza Zarrindast https://orcid.org/0000-0002-0688-5378 Journal Article 10.34172/aim.28772 2023 12 30 2024 06 12 Background: Peripheral neuropathic pain is a result of damage/illness of the peripheral nerves. The mechanisms caused by its pathophysiology are not completely understood. Methods: Imipramine is a tricyclic antidepressant that is sometimes used to treat neuropathic pain. Moreover, citicoline is considered a novel adjuvant for painful disorders such as neuropathic pain. So, a possible interaction between imipramine and citicoline on pain behavior was examined in nerve-ligated mice using tail-flick and hot plate tests. Results: The results indicated that induction of neuropathic pain by sciatic nerve ligation caused hyperalgesia in nerve-ligated mice. On the other hand, intraperitoneal (i.p.) administration of citicoline (50, 75, and 100 mg/kg), and imipramine (2.5 and 5 mg/kg) induced anti-hyperalgesic and anti-nociceptive effects in nerve-ligated mice. Furthermore, citicoline potentiated the anti-hyperalgesic and anti-nociceptive effects of imipramine when they were co-administrated in nerve-ligated mice. Interestingly, there was an additive effect between imipramine and citicoline upon induction of anti-hyperalgesic and anti-nociceptive effects in nerve-ligated mice. Conclusion: Therefore, it can be concluded that citicoline (as an adjuvant substance) enhanced the efficacy of imipramine for the modulation of pain behavior in nerve-ligated mice