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The dipeptide Phe-Phe amide attenuates signs of hyperalgesia, allodynia and nociception in diabetic mice using a mechanism involving the sigma receptor system
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
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2011 (English)In: Molecular Pain, ISSN 1744-8069, Vol. 7, 85- p.Article in journal (Refereed) Published
Abstract [en]

Background: Previous studies have demonstrated that intrathecal administration of the substance P amino-terminal metabolite substance P1-7 (SP1-7) and its C-terminal amidated congener induced antihyperalgesic effects in diabetic mice. In this study, we studied a small synthetic dipeptide related to SP1-7 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.

Place, publisher, year, edition, pages
2011. Vol. 7, 85- p.
Keyword [en]
Allodynia; Antinociception; Diabetes; Hyperalgesia; Opioid receptors; Phe-Phe amide; σ1 receptor; Substance P1-7
National Category
Medicinal Chemistry
URN: urn:nbn:se:uu:diva-165777DOI: 10.1186/1744-8069-7-85ISI: 000297405800001OAI: diva2:474704
Available from: 2012-01-09 Created: 2012-01-09 Last updated: 2012-01-11Bibliographically approved

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Carlsson, AnnaFransson, RebeccaSandström, AnjaHallberg, MathiasNyberg, Fred
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