Involvement of primary afferent C-fibres in touch-evoked pain (allodynia) induced by prostaglandin E2

Authors

  • Toshiaki Minami,

    1. 1 Department of Anaesthesiology, Osaka Medical College, Takatsuki 569-8686, Japan Departments of2Medical Chemistry and 4Anatomy, Kansai Medical University, Moriguchi 570-8506, Japan 3Department of Physiology, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan 5Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan 6Department of Molecular Neurobiology and Pharmacology, School of Medicine, University of Tokyo, Tokyo 113-0033 and CREST, Japan Science and Technology Corporation, Saitama 332-0012, Japan
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  • , 1 Emiko Okuda-Ashitaka,

    1. 1 Department of Anaesthesiology, Osaka Medical College, Takatsuki 569-8686, Japan Departments of2Medical Chemistry and 4Anatomy, Kansai Medical University, Moriguchi 570-8506, Japan 3Department of Physiology, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan 5Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan 6Department of Molecular Neurobiology and Pharmacology, School of Medicine, University of Tokyo, Tokyo 113-0033 and CREST, Japan Science and Technology Corporation, Saitama 332-0012, Japan
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  • , 2 Yuuichi Hori,

    1. 1 Department of Anaesthesiology, Osaka Medical College, Takatsuki 569-8686, Japan Departments of2Medical Chemistry and 4Anatomy, Kansai Medical University, Moriguchi 570-8506, Japan 3Department of Physiology, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan 5Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan 6Department of Molecular Neurobiology and Pharmacology, School of Medicine, University of Tokyo, Tokyo 113-0033 and CREST, Japan Science and Technology Corporation, Saitama 332-0012, Japan
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  • , 3 Satoru Sakuma,

    1. 1 Department of Anaesthesiology, Osaka Medical College, Takatsuki 569-8686, Japan Departments of2Medical Chemistry and 4Anatomy, Kansai Medical University, Moriguchi 570-8506, Japan 3Department of Physiology, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan 5Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan 6Department of Molecular Neurobiology and Pharmacology, School of Medicine, University of Tokyo, Tokyo 113-0033 and CREST, Japan Science and Technology Corporation, Saitama 332-0012, Japan
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  • , 4 Tetsuo Sugimoto,

    1. 1 Department of Anaesthesiology, Osaka Medical College, Takatsuki 569-8686, Japan Departments of2Medical Chemistry and 4Anatomy, Kansai Medical University, Moriguchi 570-8506, Japan 3Department of Physiology, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan 5Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan 6Department of Molecular Neurobiology and Pharmacology, School of Medicine, University of Tokyo, Tokyo 113-0033 and CREST, Japan Science and Technology Corporation, Saitama 332-0012, Japan
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  • 4 Kenji Sakimura,

    1. 1 Department of Anaesthesiology, Osaka Medical College, Takatsuki 569-8686, Japan Departments of2Medical Chemistry and 4Anatomy, Kansai Medical University, Moriguchi 570-8506, Japan 3Department of Physiology, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan 5Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan 6Department of Molecular Neurobiology and Pharmacology, School of Medicine, University of Tokyo, Tokyo 113-0033 and CREST, Japan Science and Technology Corporation, Saitama 332-0012, Japan
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  • , 5 Masayoshi Mishina,

    1. 1 Department of Anaesthesiology, Osaka Medical College, Takatsuki 569-8686, Japan Departments of2Medical Chemistry and 4Anatomy, Kansai Medical University, Moriguchi 570-8506, Japan 3Department of Physiology, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan 5Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan 6Department of Molecular Neurobiology and Pharmacology, School of Medicine, University of Tokyo, Tokyo 113-0033 and CREST, Japan Science and Technology Corporation, Saitama 332-0012, Japan
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  • and 6 Seiji Ito 2

    1. 1 Department of Anaesthesiology, Osaka Medical College, Takatsuki 569-8686, Japan Departments of2Medical Chemistry and 4Anatomy, Kansai Medical University, Moriguchi 570-8506, Japan 3Department of Physiology, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan 5Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan 6Department of Molecular Neurobiology and Pharmacology, School of Medicine, University of Tokyo, Tokyo 113-0033 and CREST, Japan Science and Technology Corporation, Saitama 332-0012, Japan
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Dr S. Ito, Department of Medical Chemistry, Kansai Medical University, 10–15 Fumizono, Moriguchi 570-8506, Japan.
E-mail: ito@takii.kmu.ac.jp

Abstract

Nociceptive primary afferents have the capacity to induce a state of increased excitability in dorsal horn neurons of the spinal cord or central sensitization causing thermal hyperalgesia and touch-evoked pain (allodynia). It is believed that primary afferent C-fibres become hypersensitive and induce hyperalgesia and that low-threshold Aβ-fibres are responsible for induction of allodynia, the mechanisms of which remain elusive. We previously showed that intrathecal administration of prostaglandin E2 (PGE2) and prostaglandin F (PGF) induce allodynia in conscious mice. Here we demonstrated that selective elimination of C-fibres by neonatal capsaicin treatment resulted in the disappearance of allodynia induced by PGE2, but not that by PGF. PGE2-induced allodynia was not observed in N-methyl-D-aspartate (NMDA) receptor ε1 subunit knockout mice and was sensitive to morphine. In contrast, PGF-induced allodynia was not observed in NMDA ε4 subunit knockout mice and was insensitive to morphine. Furthermore, while PGF showed a capsaicin-insensitive feeble facilitatory action on evoked excitatory postsynaptic currents in dorsal horn neurons, PGE2 induced a long-lasting facilitation of evoked excitatory postsynaptic currents in a capsaicin-sensitive manner. Taken together, the present study demonstrates that there are two pathways for induction of allodynia and that capsaicin-sensitive C-fibres may participate in PGE2-induced allodynia.

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