effect of substance P₁–₇ amide on nociceptive threshold in diabetic mice

• Published in: Peptides (New York, N.Y. : 1980) Vol. 32; no. 1; pp. 93 - 98
• Main Authors: Ohsawa, Masahiro, Carlsson, Anna, Asato, Megumi, Koizumi, Takayuki, Nakanishi, Yuki, Fransson, Rebecca, Sandström, Anja, Hallberg, Mathias, Nyberg, Fred, Kamei, Junzo
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 2011; Elsevier
• Subjects: agonists; analgesic effect; Analgesics; Analgesics - administration & dosage; Analgesics - pharmacology; Animals; antagonists; Antinociception; Biological and medical sciences; Diabetes; Diabetes Mellitus, Experimental - metabolism; Diabetes. Impaired glucose tolerance; Dose-Response Relationship, Drug; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; FARMACI; Fundamental and applied biological sciences. Psychology; Injections, Spinal; mechanism of action; Medical sciences; metabolites; Mice; Mice, Inbred ICR; naloxone; Neuropharmacology; Nociceptors - metabolism; Opioid receptors; Pain Measurement; Pain Threshold - drug effects; Peptide Fragments - administration & dosage; Peptide Fragments - pharmacology; Pharmacology. Drug treatments; PHARMACY; Sigma receptor; substance P; Substance P - administration & dosage; Substance P - pharmacology; Substance P fragment substance P1-7; Substance P1-7 amide; substances; Vertebrates: endocrinology; Endocrinopathy; Opioid receptors; Substance P; Diabetes mellitus; Opioid receptor; Rodentia; Sigma receptor; Antinociception; Neuropeptide; Substance P fragment substance P; Vertebrata; Mammalia; Analgesic; Mouse; amide; Animal; Diabetes; Tachykinin
• ISSN: 0196-9781; 1873-5169; 1873-5169
• DOI: 10.1016/j.peptides.2010.09.029

We previously demonstrated that intrathecal treatment with substance P metabolite substance P₁–₇ induced anti-hyperalgesia in diabetic mice. In the present study, we have used a synthetic analog of this peptide, the substance P₁–₇ 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 P₁–₇ 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 P₁–₇ amide was higher in both diabetic and non-diabetic mice in comparison with the native substance P₁–₇. The antinociceptive effect of substance P₁–₇ 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 P₁–₇ amide was partly reversed by the σ₁ receptor agonist (+)-pentazocine, suggesting a possible involvement of the σ₁ receptor for the action of this peptide. These results suggest that the actions of substance P₁–₇ amide mimic the effects of the native substance P fragment but with higher potency and that the mechanisms for its action may involve the σ₁ receptor system.