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

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

Carmela Parenti, Agostino Marrazzo, Giuseppina Aricò, Rosalba Parenti, Lorella Pasquinucci, Simone Ronsisvalle, Giuseppe Ronsisvalle, Giovanna Maria Scoto 

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.