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In Vivo Signal Transduction of Tetrodotoxin-Sensitive Nociceptive Responses by Substance P Given into the Planta of the Mouse Hind Limb

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Abstract

1. We developed a simple and sensitive peripheral analgesic test in mice.

2. Substance P (SP) given into the planta (i.pl.) of the mouse hind limb produced a flexor response. The flexor response was dependent on SP doses (0.1–100 pmol, i.pl.). When SP (10 pmol) was given every 5 min, there were stable flexor responses. These nociceptive responses were completely abolished by CP-96,345, a neurokinin 1 receptor antagonist.

3. SP-induced responses were also blocked by several signal transduction-related compounds, such as tetrodotoxin, EGTA, and U73122, a selective phospholipase C inhibitor.

4. These findings suggest that SP depolarizes peripheral nerve endings, possibly through inositol trisphosphate (Ins P3)-gated Ca2+ influx, followed by induction of action potentials in the peripheral axons of primary afferent neurons.

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Authors and Affiliations

  1. Department of Molecular Pharmacology and Neuroscience, Nagasaki University School of Pharmaceutical Sciences, 1-14 Bunkyo-machi, Nagasaki, 852-8521, Japan

    Makoto Inoue, Shogo Tokuyama, Hiroyuki Nakayamada & Hiroshi Ueda

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  1. Makoto Inoue
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  2. Shogo Tokuyama
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  3. Hiroyuki Nakayamada
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  4. Hiroshi Ueda
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Inoue, M., Tokuyama, S., Nakayamada, H. et al. In Vivo Signal Transduction of Tetrodotoxin-Sensitive Nociceptive Responses by Substance P Given into the Planta of the Mouse Hind Limb. Cell Mol Neurobiol 18, 555–561 (1998). https://doi.org/10.1023/A:1026335611162

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  • DOI: https://doi.org/10.1023/A:1026335611162

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