Effects of a Selective Sigma 1 Antagonist Compound on Inflammatory Pain

The compound (-)-MRV3 [(-)-methyl (1S,2R)-2-[(4-hydroxy-4-phenylpiperidin-1-yl)-methyl]-1-phenylcyclopropanecarboxylate] has an assessed antagonist sigma 1 (sigma(1)) profile and showed improved sigma(1)/sigma(2) selectivity with respect to the parent compound (+)-MR200. The sigma(1) receptor is reported to play a role in both central sensitization and pain hypersensitivity, which suggests a potential use of sigma (1) antagonists for the treatment of persistent pain conditions. The present study was performed to assess the effects of the selective sigma(1) antagonist (-)-MRV3, in carrageenan-induced inflammatory hyperalgesia, allodynia, and edema. Mechanical allodynia with a series of calibrated von Frey's filaments, thermal hyperalgesia with plantar test, and edema evaluation with a plethysmometer were measured. Subcutaneous (s.c.) treatment with (-)-MRV3 (1, 2, 3, 4, 5 mg/kg) dose-dependently reduced allodynia and hyperalgesia induced by intraplantar carrageenan. Furthermore, treatment with (-)-MRV3 (3 mg/kg s.c.) also inhibited paw edema with a significant inhibition of 37.82 % 3 h after carrageenan treatment. These results provide a strong basis for the use of sigma(1) receptor antagonists in the treatment of inflammatory pain.