Potentiation of Imipramine-Induced Anti-hyperalgesic and Anti-Nociceptive Effects by Citicoline in the Sciatic Nerve Ligated Mice

Arch Iran Med. 2024 Aug 1;27(8):456-464. doi: 10.34172/aim.28772. Epub 2024 Aug 1.

Abstract

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.

Keywords: Citicoline; Imipramine; Nerve-ligated Mice; Neuropathic pain.

MeSH terms

  • Analgesics / pharmacology
  • Analgesics / therapeutic use
  • Animals
  • Antidepressive Agents, Tricyclic / pharmacology
  • Antidepressive Agents, Tricyclic / therapeutic use
  • Cytidine Diphosphate Choline* / pharmacology
  • Cytidine Diphosphate Choline* / therapeutic use
  • Disease Models, Animal
  • Drug Synergism
  • Hyperalgesia* / drug therapy
  • Hyperalgesia* / etiology
  • Imipramine* / pharmacology
  • Imipramine* / therapeutic use
  • Ligation
  • Male
  • Mice
  • Neuralgia* / drug therapy
  • Neuralgia* / etiology
  • Nootropic Agents / pharmacology
  • Nootropic Agents / therapeutic use
  • Pain Measurement
  • Sciatic Nerve* / drug effects

Substances

  • Imipramine
  • Cytidine Diphosphate Choline
  • Analgesics
  • Antidepressive Agents, Tricyclic
  • Nootropic Agents