Assessment of the antinociceptive and ulcerogenic activity of the tapentadol-diclofenac combination in rodents

Drug Dev Res. 2018 Feb;79(1):38-44. doi: 10.1002/ddr.21420. Epub 2018 Jan 3.

Abstract

Preclinical Research & Development The objective of the present study was to evaluate the tapentadol-diclofenac combination in three dose-ratios in the mouse acetic acid-induced visceral pain and their ulcerogenic activity on the stomachal mucous. Dose-response curves were generated for tapentadol, diclofenac, and their combination in the acetic acid-induced writhing test in mice. Moreover, the stomachs of animals were surgically removal and gastrointestinal ulcerogenic action of the combination was assessed. The isobolographic analysis, interaction index, and ANOVA were used to analyze the data. The isobolographic analysis and interaction index showed a similar antinociceptive activity for the three combinations of the analgesic mixture. Moreover, tapentadol and the proportions 1:1 or 3:1 of the analgesic combination caused a mild gastrointestinal damage. These data indicate that the systemic co-administration of tapentadol and diclofenac produced a synergistic interaction in the acetic acid-induced visceral pain test with an acceptable gastric damage profile in mice.

Keywords: acetic acid-induced writhing test; antinociceptive synergistic interaction; diclofenac; gastrointestinal damage; tapentadol.

MeSH terms

  • Acetic Acid
  • Analgesics / therapeutic use*
  • Animals
  • Diclofenac / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Male
  • Mice
  • Phenols / therapeutic use*
  • Stomach / drug effects
  • Stomach / pathology
  • Stomach Ulcer / chemically induced
  • Stomach Ulcer / pathology
  • Tapentadol
  • Visceral Pain / chemically induced
  • Visceral Pain / drug therapy*

Substances

  • Analgesics
  • Phenols
  • Diclofenac
  • Tapentadol
  • Acetic Acid