The dipeptide Phe-Phe amide attenuates signs of hyperalgesia, allodynia and nociception in diabetic mice using a mechanism involving the sigma receptor system

Molecular Pain

关键词: Allodynia;    Antinociception;    Diabetes;    Hyperalgesia;    Opioid receptors;    Phe-Phe amide;    σ₁ receptor;    Substance P_1-7;   

DOI  :  10.1186/1744-8069-7-85

来源: DOAJ

【 摘 要 】

Abstract

Background

Previous studies have demonstrated that intrathecal administration of the substance P amino-terminal metabolite substance P_1-7 (SP_1-7) and its C-terminal amidated congener induced antihyperalgesic effects in diabetic mice. In this study, we studied a small synthetic dipeptide related to SP_1-7 and endomorphin-2, i.e. Phe-Phe amide, using the tail-flick test and von Frey filament test in diabetic and non-diabetic mice.

Results

Intrathecal treatment with the dipeptide increased the tail-flick latency in both diabetic and non-diabetic mice. This effect of Phe-Phe amide was significantly greater in diabetic mice than non-diabetic mice. The Phe-Phe amide-induced antinociceptive effect in both diabetic and non-diabetic mice was reversed by the σ₁ receptor agonist (+)-pentazocine. Moreover, Phe-Phe amide attenuated mechanical allodynia in diabetic mice, which was reversible by (+)-pentazocine. The expression of spinal σ1 receptor mRNA and protein did not differ between diabetic mice and non-diabetic mice. On the other hand, the expression of phosphorylated extracellular signal-regulated protein kinase 1 (ERK1) and ERK2 proteins was enhanced in diabetic mice. (+)-Pentazocine caused phosphorylation of ERK1 and ERK2 proteins in non-diabetic mice, but not in diabetic mice.

Conclusions

These results suggest that the spinal σ₁ receptor system might contribute to diabetic mechanical allodynia and thermal hyperalgesia, which could be potently attenuated by Phe-Phe amide.

【 授权许可】

Unknown