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Reduced antinociception and plasma extravasation in mice lacking a neuropeptide Y receptor

Naturevolume 409pages513517 (2001) | Download Citation

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Abstract

Neuropeptide Y (NPY) is believed to exert antinociceptive actions by inhibiting the release of substance P and other ‘pain neurotransmitters’ in the spinal cord dorsal horn1,2,3. However, the physiological significance and potential therapeutic value of NPY remain obscure4. It is also unclear which receptor subtype(s) are involved. To identify a possible physiological role for the NPY Y1 receptor in pain transmission, we generated NPY Y1 receptor null mutant (Y1-/-) mice by homologous recombination techniques. Here we show that Y1-/- mice develop hyperalgesia to acute thermal, cutaneous and visceral chemical pain, and exhibit mechanical hypersensitivity. Neuropathic pain is increased, and the mice show a complete absence of the pharmacological analgesic effects of NPY. In the periphery, Y1 receptor activation is sufficient and required for substance P release and the subsequent development of neurogenic inflammation and plasma leakage. We conclude that the Y1 receptor is required for central physiological and pharmacological NPY-induced analgesia and that its activation is both sufficient and required for the release of substance P and initiation of neurogenic inflammation.

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Acknowledgements

We thank L. Klevenvall-Fridvall for technical assistance and L. Johansson for secretarial assistance. This research was supported by the Swedish Medical Research Council the Biotechnology Program of the European Union and the Swedish Cancer Society.

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Author notes

  1. Philippe Naveilhan, Hessameh Hassani and Peter Thorén: These authors contributed equally to this work

Affiliations

  1. Laboratory of Molecular Neurobiology Department of Medical Biochemistry and Biophysics, and

    • Philippe Naveilhan
    • , Hessameh Hassani
    • , Guilherme Lucas
    •  & Patrik Ernfors
  2. Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, S-17177, Sweden

    • Peter Thorén
  3. Department of Medical Laboratory Sciences and Technology, Division of Clinical Neurophysiology, Huddinge University Hospital, Karolinska Institute, Huddinge, S-14186, Sweden

    • Karin Hygge Blakeman
    • , Jing-Xia Hao
    • , Xiao-Jun Xu
    •  & Zsuzsanna Wiesenfeld-Hallin

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Correspondence to Patrik Ernfors.

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https://doi.org/10.1038/35054063

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