Capsaicin-Induced Glutamate Release Is Implicated in Nociceptive Processing Through Activation of Ionotropic Glutamate Receptors and Group I Metabotropic Glutamate Receptor in Primary Afferent Fibers

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概要

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• Glutamate (Glu) is the major excitatory neurotransmitter in the central nervous system. The role of peripheral Glu and Glu receptors (GluRs) in nociceptive transmission is, however, still unclear. In the present study, we examined Glu levels released in the subcutaneous perfusate of the rat hind instep using a microdialysis catheter and the thermal withdrawal latency using the Plantar Test following injection of drugs associated with GluRs with/without capsaicin into the hindpaw. The injection of capsaicin into the rat hind instep caused an increase of Glu level in the s.c. perfusate. Capsaicin also significantly decreased withdrawal latency to irradiation. These effects of capsaicin were inhibited by pretreatment with capsazepine, a transient receptor potential vanilloid receptor 1 (TRPV1) competitive antagonist. Capsaicin-induced Glu release was also suppressed by combination with each antagonist of ionotropic GluRs (iGluRs: NMDA/AMPA receptors) and group I metabotropic GluR (mGluR), but not group II and group III mGluRs. Furthermore, these GluRs antagonists showed remarkable inhibition against capsaicin-induced thermal hyperalgesia. These results suggest that Glu is released from the peripheral endings of small-diameter afferent fibers by noxious stimulation and then activates peripheral iGluRs and group I mGluR in development and/or maintenance of nociception. Furthermore, the activation of peripheral NMDA/AMPA receptors and group I mGluR may be important in mechanisms whereby capsaicin evokes nociceptive responses.

• 2009-02-20

著者

• Jin You-hong

  Department Of Pharmacology Osaka University Graduate School Of Dentistry

• TAKEMURA Motohide

  Department of Oral Anatomy, Osaka University Faculty of Dentistry

• Koike Yuichi

  Drug Metabolism And Clinical Pharmacokinetics Ohu University School Of Pharmaceutical Science

• Yonehara Norifumi

  Division Of Pharmacology Ohu University School Of Pharmaceutical Science

• YAMAKI Fumiko

  Division of Pharmacology, Ohu University School of Pharmaceutical Science

• FURUYAMA Akira

  Department of Oral Physiology, Ohu University School of Dentistry

• Takemura Motohide

  Department Of Oral Anatomy And Neurobiology Osaka University Graduate School Of Dentistry

• Yamaki Fumiko

  Division Of Pharmacology Ohu University School Of Pharmaceutical Science

• Furuyama Akira

  Department Of Oral Physiology Ohu University School Of Dentistry

• Furuyama Akira

  Department Of Developmental Biology And Neurosciences Graduate School Of Lifesciences Tohoku Univers

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• Capsaicin-Induced Glutamate Release Is Implicated in Nociceptive Processing Through Activation of Ionotropic Glutamate Receptors and Group I Metabotropic Glutamate Receptor in Primary Afferent Fibers
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