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
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 ins...
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| Format: | Article |
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Elsevier
2009-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319312782 |
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| author | You-Hong Jin Fumiko Yamaki Motohide Takemura Yuichi Koike Akira Furuyama Norifumi Yonehara |
| author_facet | You-Hong Jin Fumiko Yamaki Motohide Takemura Yuichi Koike Akira Furuyama Norifumi Yonehara |
| author_sort | You-Hong Jin |
| collection | DOAJ |
| description | 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. Keywords:: glutamate, peripheral, capsaicin, thermal hyperalgesia, microdialysis |
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| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-04-12T19:11:31Z |
| publishDate | 2009-01-01 |
| publisher | Elsevier |
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| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-b3ce78ef907d46669bdf252a54137ef42022-12-22T03:19:51ZengElsevierJournal of Pharmacological Sciences1347-86132009-01-011092233241Capsaicin-Induced Glutamate Release Is Implicated in Nociceptive Processing Through Activation of Ionotropic Glutamate Receptors and Group I Metabotropic Glutamate Receptor in Primary Afferent FibersYou-Hong Jin0Fumiko Yamaki1Motohide Takemura2Yuichi Koike3Akira Furuyama4Norifumi Yonehara5Departments of Pharmacology and Suita, Osaka 565-0871, JapanDivisions of Pharmacology and Koriyama, Fukushima 963-8611, JapanOral Anatomy and Neurobiology, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871, JapanDrug Metabolism and Clinical Pharmacokinetics, Ohu University School of Pharmaceutical Science, Koriyama, Fukushima 963-8611, JapanDepartment of Oral Physiology, Ohu University School of Dentistry, Koriyama, Fukushima 963-8611, JapanDivisions of Pharmacology and Koriyama, Fukushima 963-8611, Japan; Corresponding author. n-yonehara@pha.ohu-u.ac.jpGlutamate (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. Keywords:: glutamate, peripheral, capsaicin, thermal hyperalgesia, microdialysishttp://www.sciencedirect.com/science/article/pii/S1347861319312782 |
| spellingShingle | You-Hong Jin Fumiko Yamaki Motohide Takemura Yuichi Koike Akira Furuyama Norifumi Yonehara 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 Journal of Pharmacological Sciences |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319312782 |
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