Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2007093 | Peptides | 2009 | 8 Pages |
Abstract
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 50Â pmol) injected i.t. alone did not alter capsaicin-induced nociception, whereas substance P at a higher dose of 100Â 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 (50Â 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-Pro2, d-Phe7]substance P (1-7), an inhibitor of [3H] 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.
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Authors
Takaaki Komatsu, Mika Sasaki, Kengo Sanai, Hikari Kuwahata, Chikai Sakurada, Minoru Tsuzuki, Yohko Iwata, Shinobu Sakurada, Tsukasa Sakurada,