The antagonistic effect of the sigma 1 receptor ligand (+)-MR200 on persistent pain induced by inflammation

Inflamm Res. 2014 Mar;63(3):231-7. doi: 10.1007/s00011-013-0692-2. Epub 2013 Dec 8.

Abstract

Objective and design: The sigma 1 (σ1) receptor, which is widely distributed in the CNS in areas that are known to be important for pain control, may play a role in persistent pain characterized by the hypersensitivity of nociceptive transmission. Here, we investigated the effect of σ1 blockade in an inflammatory pain model.

Treatment and methods: An intraplantar injection of carrageenan (2 %) was used to induce paw inflammation. The effects of the σ1 antagonist (+)-MR200, given subcutaneously at a dose of 0.1, 0.25, 0.5,1, 1.5, and 2 mg/kg prior to injection of carrageenan, on inflammatory pain and inflammation were assessed. Mechanical allodynia with von Frey filaments, thermal hyperalgesia with the plantar test and edema evaluation with a plethysmometer were measured. Intergroup comparisons were assessed by one- or two-way analysis of variance when appropriate, followed by post-hoc tests (Dunnett's test for one-way or Bonferroni for two-way ANOVA).

Results: (+)-MR200 dose-dependently prevented allodynia and hyperalgesia induced by carrageenan. Furthermore, it reduced paw edema with a significant inhibition percentage of 37.82 % at 3 h after carrageenan treatment.

Conclusions: The blockade of the σ1 receptor with the selective antagonist (+)-MR200 may contribute to the suppression of the typical symptoms of inflammatory pain.

MeSH terms

  • Animals
  • Carrageenan
  • Chronic Pain / drug therapy*
  • Chronic Pain / etiology
  • Cyclopropanes / therapeutic use*
  • Dose-Response Relationship, Drug
  • Edema / chemically induced
  • Edema / drug therapy
  • Edema / pathology
  • Foot / pathology
  • Hot Temperature
  • Hyperalgesia / drug therapy
  • Inflammation / chemically induced
  • Inflammation / complications*
  • Male
  • Physical Stimulation
  • Piperidines / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, sigma / antagonists & inhibitors*
  • Sigma-1 Receptor

Substances

  • (+)-methyl 2-((4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)methyl)-1-phenylcyclopropanecarboxylate
  • Cyclopropanes
  • Piperidines
  • Receptors, sigma
  • Carrageenan