The impact of Dimethyl itaconate on c-Fos expression in the spinal cord in experimental pain models

Neurosci Lett. 2024 Apr 1:828:137741. doi: 10.1016/j.neulet.2024.137741. Epub 2024 Mar 21.

Abstract

Itaconate has been found to have potent anti-inflammatory effects and is being explored as a potential treatment for inflammatory diseases. However, its ability to relieve nociception and the mechanisms behind it are not yet understood. Our research aims to investigate the nociception-relieving properties of dimethyl itaconate (DMI) in the formalin test and writhing test. In male Wistar rats, Itaconic acid was injected intraperitoneally (i.p.). The formalin test and writhing test were conducted to determine the nociceptive behaviors. The spinal cords were removed from the rats and analyzed for c-fos protein expression. The study found that administering DMI 10 and 20 mg/kg reduced nociception in formalin and writhing tests. Injection of formalin into the periphery of the body led to an increase in the expression of c-fos in the spinal cord, which was alleviated by DMI 20 mg/kg. Similarly, acetic acid injection into the peritoneal cavity caused an increase in c-fos expression in the spinal cord, which was then reduced by 20 mg/kg. According to our findings, DMI reduced nociception in rats during the formalin and writhing tests. One possible explanation for this outcome is that the decrease in c-fos protein expression may be attributed to the presence of DMI.

Keywords: C-fos; Dimethyl itaconate; Formalin test; Writhing test.

MeSH terms

  • Animals
  • Formaldehyde / pharmacology
  • Male
  • Pain* / drug therapy
  • Pain* / metabolism
  • Proto-Oncogene Proteins c-fos* / drug effects
  • Proto-Oncogene Proteins c-fos* / metabolism
  • Rats
  • Rats, Wistar
  • Spinal Cord / metabolism
  • Succinates* / metabolism
  • Succinates* / pharmacology

Substances

  • dimethyl itaconate
  • Formaldehyde
  • itaconic acid
  • Proto-Oncogene Proteins c-fos
  • Succinates