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Involvement of Peripheral NMDA Receptor in Melittin-Induced Thermographic Flare

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Abstract

Intradermal injection of an active compound of European honeybee toxin, melittin, into the forearm in humans produces temporary pain and evokes sustained increase of local skin temperature. This increase of skin temperature is suppressed by the pretreatment of a voltage gated sodium channel blocker, lidocaine, suggesting that neurogenic inflammation is involved in the skin temperature increase after the melittin treatment. In this study, we tested a hypothesis that the melittin-induced skin temperature increase is augmented by an N-methyl-D-aspartate (NMDA) glutamate receptor that is present on the peripheral terminals of cutaneous primary afferents. Skin temperature was examined after the local application of incremental doses of melittin by a computer-assisted-thermography in pentobarbital-anesthetized rats. Local subcutaneous glutamate was collected through a microdialysis probe and glutamate levels were measured by a high pressure liquid chromatography with electrochemical detection method. Intraplantar injection of melittin resulted in the increase of subcutaneous glutamate levels and the increase of local skin temperature, which was partially attenuated by co-injection of an NMDA receptor antagonist, MK-801. In addition, intraplantar injection of NMDA itself increased the local skin temperature. Our data suggest that melittin-induced increase of skin temperature is enhanced through the activation of peripheral NMDA receptors by locally released glutamate. We suggest that topical administration of NMDA receptor antagonists could be an effective treatment of neuro-inflammatory pain.

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Acknowledgments

The authors wish to thank Dr Hirotoshi Kitagawa for their technical advice on microdialysis methods. The authors are grateful to Dr. Seiji Hitoshi for his helpful revision of the manuscript.

Conflict of interest

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Physiology, Shiga University of Medical Science, Seta Otsu, 520-2192, Japan

    Narihito Iwashita & Natsu Koyama

  2. Department of Anesthesiology, Shiga University of Medical Science, Seta Otsu, 520-2192, Japan

    Narihito Iwashita & Shuichi Nosaka

Authors
  1. Narihito Iwashita
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  2. Shuichi Nosaka
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  3. Natsu Koyama
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Correspondence to Natsu Koyama.

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Iwashita, N., Nosaka, S. & Koyama, N. Involvement of Peripheral NMDA Receptor in Melittin-Induced Thermographic Flare. Neurochem Res 37, 2222–2228 (2012). https://doi.org/10.1007/s11064-012-0849-3

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  • DOI: https://doi.org/10.1007/s11064-012-0849-3

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