The effect of substance P 1–7 amide on nociceptive threshold in diabetic mice

Abstract

We previously demonstrated that intrathecal treatment with substance P metabolite substance P 1–7 induced anti-hyperalgesia in diabetic mice. In the present study, we have used a synthetic analog of this peptide, the substance P 1–7 amide, showing higher binding affinitiy than the native heptapeptide, for studies of the tail-flick response in diabetic and non-diabetic mice. Intrathecal injection of substance P 1–7 amide produced prolongation of the tail-flick latency in both diabetic and non-diabetic mice, an effect that was more pronounced in diabetic mice than non-diabetic mice. Moreover, the observed antinociceptive potency of the substance P 1–7 amide was higher in both diabetic and non-diabetic mice in comparison with the native substance P 1–7. The antinociceptive effect of substance P 1–7 amide was reversed by naloxone but not by the selective opioid receptor antagonist β-funaltrexamine, naltrindole or nor-binaltorphimine, selective for the μ-, δ- or κ-opioid receptor, respectively. In addition, the antinociceptive effect induced by substance P 1–7 amide was partly reversed by the σ 1 receptor agonist (+)-pentazocine, suggesting a possible involvement of the σ 1 receptor for the action of this peptide. These results suggest that the actions of substance P 1–7 amide mimic the effects of the native substance P fragment but with higher potency and that the mechanisms for its action may involve the σ 1 receptor system.