title: 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.
abstract: 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.
authors.affiliation: Department of Pharmacology, Osaka University Graduate School of Dentistry, Suita, Japan.
authors.forename: You-Hong
authors.initials: YH
authors.lastname: Jin
authors.forename: Fumiko
authors.initials: F
authors.lastname: Yamaki
authors.forename: Motohide
authors.initials: M
authors.lastname: Takemura
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Koike
authors.forename: Akira
authors.initials: A
authors.lastname: Furuyama
authors.forename: Norifumi
authors.initials: N
authors.lastname: Yonehara
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D006930:Hyperalgesia / Q000378:metabolism; D008297:Male; D009412:Nerve Fibers / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D018689:Sensory System Agents / Q000494:pharmacology*; D050916:TRPV Cation Channels / Q000819:agonists; D013997:Time Factors
chemical_list: D018091:Receptors, AMPA; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D018689:Sensory System Agents; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D018698:Glutamic Acid; C071423:capsazepine; D002211:Capsaicin