Evaluation of therapeutic effect of low dose naltrexone in experimentally-induced Crohn's disease in rats

Neuropeptides. 2016 Oct:59:39-45. doi: 10.1016/j.npep.2016.06.003. Epub 2016 Jun 22.


Background and aim: Crohn's disease is a relapsing inflammatory condition afflicting the digestive tract. Drugs used for treatment of Crohn's disease may be associated with serious side effects. Endogenous opioid peptides modulate inflammatory cytokine production. Opioid antagonists have been shown to play a role in healing and repair of tissues. This work was designed to detect the possible beneficial effects of opioid antagonist naltrexone in indomethacin-induced Crohn's disease in rats.

Experimental approach: Enteritis was induced in male albino rats by two subcutaneous injection of indomethacin in a dose of 7.5mg/kg 24h apart started on day one. Salfasalazine, naltrexone and their combination were administered orally from day one of induction of enteritis to day 10. Disease activity index, serum levels of C-reactive protein and tumor necrosis factor-α, macroscopic and microscopic pathological scores and in vitro motility studies were evaluated.

Results: Induction of enteritis resulted in significant increase of disease activity index, significant elevation of serum levels of C-reactive protein and tumor necrosis factor-α, significant deterioration of pathological scores and significant increase in the mean contractility response of the isolated ileal segments compared with normal untreated rats. Treatment with sulfasalazine, low dose of natrexone or their combination resulted in significant improvement of all measured parameters compared with enteritis group.

Conclusion: The current finding could provide new interesting opportunity for developing new therapeutic approaches for treatment of Crohn's disease. Use of naltrexone, especially in small dose, has little side effects making it of interest for treatment of Crohn's disease. Also, it provides the possibility of reduced doses of other drugs if it is used as combined therapy.

Keywords: Crohn's disease; DAI; Indomethacin; Naltrexone; Sulfasalazine.

MeSH terms

  • Animals
  • Crohn Disease / chemically induced
  • Crohn Disease / drug therapy*
  • Crohn Disease / pathology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Ileum / drug effects*
  • Ileum / pathology
  • Indomethacin
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / pathology
  • Male
  • Naltrexone / pharmacology
  • Naltrexone / therapeutic use*
  • Narcotic Antagonists / pharmacology
  • Narcotic Antagonists / therapeutic use*
  • Rats
  • Sulfasalazine / pharmacology
  • Sulfasalazine / therapeutic use
  • Treatment Outcome


  • Narcotic Antagonists
  • Sulfasalazine
  • Naltrexone
  • Indomethacin