Intrathecal substance P augments morphine-induced antinociception: possible relevance in the production of substance P N-terminal fragments
| Autor: | Chikai Sakurada, Tsukasa Sakurada, Minoru Tsuzuki, Takaaki Komatsu, Shinobu Sakurada, Yohko Iwata, Mika Sasaki, Hikari Kuwahata, Kengo Sanai |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Physiology Pain Substance P Mice Inbred Strains Pharmacology Biochemistry Antibodies Cellular and Molecular Neuroscience chemistry.chemical_compound Subcutaneous injection Mice Endocrinology medicine Animals Protease Inhibitors Neprilysin Injections Spinal Pain Measurement Dose-Response Relationship Drug Morphine Phosphoramidon Glycopeptides Drug Synergism Peptide Fragments Nociception chemistry Spinal Cord Capsaicin Licking medicine.drug |
| Zdroj: | Peptides. 30(9) |
| ISSN: | 1873-5169 |
| Popis: | The present study sought to examine the mechanism of substance P to modulate the antinociceptive action of intrathecal (i.t.) morphine in paw-licking/biting response evoked by subcutaneous injection of capsaicin into the plantar surface of the hindpaw in mice. The i.t. injection of morphine inhibited capsaicin-induced licking/biting response in a dose-dependent manner. Substance P (25 and 50 pmol) injected i.t. alone did not alter capsaicin-induced nociception, whereas substance P at a higher dose of 100 pmol significantly reduced the capsaicin response. Western blots showed the constitutive expression of endopeptidase-24.11 in the dorsal and ventral parts of lumbar spinal cord of mice. The N-terminal fragment of substance P (1-7), which is known as a major product of substance P by endopeptidase-24.11, was more effective than substance P on capsaicin-induced nociception. Combination treatment with substance P (50 pmol) and morphine at a subthreshold dose enhanced the antinociceptive effect of morphine. The enhanced effect of the combination of substance P with morphine was reduced significantly by co-administration of phosphoramidon, an inhibitor of endopeptidase-24.11. Administration of D-isomer of substance P (1-7), [D-Pro(2), D-Phe(7)]substance P (1-7), an inhibitor of [(3)H] substance P (1-7) binding, or antisera against substance P (1-7) reversed the enhanced antinociceptive effect by co-administration of substance P and morphine. Taken together these data suggest that morphine-induced antinociception may be enhanced through substance P (1-7) formed by the enzymatic degradation of i.t. injected substance P in the spinal cord. |
| Databáze: | OpenAIRE |
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