Effects of a selective sigma 1 antagonist compound on inflammatory pain

Inflammation. 2014 Feb;37(1):261-6. doi: 10.1007/s10753-013-9736-6.

Abstract

The compound (−)-MRV3 [(−)-Methyl (1S,2R)-2-[(4-Hydroxy-4-phenylpiperidin-1-yl)-methyl]-1-phenylcyclopropanecarboxylate] has an assessed antagonistsigma 1 (σ1) profile and showed improved σ1/σ2 selectivity with respect to the parent compound(+)-MR200. The σ1 receptor is reported to play arole in both central sensitization and pain hypersensitivity,which suggests a potential use of σ1 antagonists forthe treatment of persistent pain conditions. The present study was performed to assess the effects of theselective σ1 antagonist (−)-MRV3, in carrageenan-inducedinflammatory hyperalgesia, allodynia and edema.Mechanical allodynia with a series of calibratedvon Frey’s filaments, thermal hyperalgesia with plantartest and edema evaluation with a plethysmometerwere measured. Subcutaneous (s.c.) treatment with(−)-MRV3 (1, 2, 3, 4, 5 mg/kg) dose-dependentlyreduced allodynia and hyperalgesia induced byintraplantar carageenan. Furthermore, treatment with(−)-MRV3 (3 mg/kg s.c.) also inhibited paw edemawith a significant inhibition of 61.53 % 3 h aftercarrageenan treatment [corrected]. These results provide a strongbasis for the use of σ1 receptor antagonists in thetreatment of inflammatory pain.

MeSH terms

  • Animals
  • Carrageenan
  • Cyclopropanes / pharmacology
  • Disease Models, Animal
  • Edema / chemically induced
  • Edema / drug therapy*
  • Hyperalgesia / chemically induced
  • Hyperalgesia / drug therapy*
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Male
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / metabolism
  • Pain / chemically induced
  • Pain / drug therapy*
  • Pain Measurement
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, sigma / antagonists & inhibitors*

Substances

  • Cyclopropanes
  • Receptors, sigma
  • cyclopropanecarboxylic acid
  • Nitric Oxide
  • Carrageenan
  • Nitric Oxide Synthase