Thiazolidine Derivatives Attenuate Carrageenan-Induced Inflammatory Pain in Mice

Drug Des Devel Ther. 2021 Feb 4:15:369-384. doi: 10.2147/DDDT.S281559. eCollection 2021.

Abstract

Background: Peripheral inflammation leads to the development of persistent thermal hyperalgesia and mechanical allodynia associated with increased expression of interleukin-1β (IL-1β) in the spinal cord. The aim of the present study was to investigate the effects of thiazolidine derivatives, 1b ([2-(2-hydroxyphenyl)-1,3-thiazolidin-4-yl](morpholin-4-yl)methanone) and 1d (2-hydroxy-4-{[2-(2-hydroxyphenyl)-1,3-thiazolidine-4-carbonyl]amino}benzoic acid), on thermal hyperalgesia, mechanical allodynia and on IL-1β expression during carrageenan-induced inflammation in the spinal cord in mice. Inflammatory pain was induced by injecting 1% carrageenan into the right hind paw of the mice.

Methods: The animals were administered thiazolidine derivatives, 1b and 1d (1 mg/kg, 3 mg/kg, or 10 mg/kg), intraperitoneally 30 minutes before carrageenan administration. The animals' behavior was evaluated by measuring thermal hyperalgesia, mechanical allodynia, and motor coordination. The IL-1β expression was measured by enzyme-linked immunosorbent assay. Acute and sub-acute toxicity studies were conducted to evaluate the toxicity profile of compounds.

Results: Treatment with the thiazolidine derivative, 1b and 1d, attenuated carrageenan-induced thermal hyperalgesia and mechanical allodynia at doses of 1 mg/kg, 3 mg/kg, and 10 mg/kg. No motor coordination deficits were observed in animals. The compounds also reduced IL-1β expression in the spinal cord of mice. Acute and sub-acute toxicity studies revealed that both compounds were safe.

Conclusion: The compounds exhibit promising activity against inflammatory pain due to their ability to produce anti-hyperalgesic and anti-allodynic effects and to inhibit IL-1β expression in the spinal cord.

Keywords: IL-1β; inflammatory pain; mechanical allodynia; thermal hyperalgesia; thiazolidine derivatives.

MeSH terms

  • Animals
  • Carrageenan / administration & dosage
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Hyperalgesia / chemically induced
  • Hyperalgesia / drug therapy*
  • Hyperalgesia / metabolism
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Molecular Structure
  • Pain / chemically induced
  • Pain / drug therapy*
  • Pain / metabolism
  • Structure-Activity Relationship
  • Thiazolidines / therapeutic use*

Substances

  • Thiazolidines
  • Carrageenan