title: Expression of vesicular glutamate transporters in transient receptor potential melastatin 8 (TRPM8)-positive dental afferents in the mouse.
abstract: Transient receptor potential melastatin 8 (TRPM8) is activated by innocuous cool and noxious cold and plays a crucial role in cold-induced acute pain and pain hypersensitivity. To help understand the mechanism of TRPM8-mediated cold perception under normal and pathologic conditions, we used light microscopic immunohistochemistry and Western blot analysis in mice expressing a genetically encoded axonal tracer in TRPM8-positive (+) neurons. We investigated the coexpression of TRPM8 and vesicular glutamate transporter 1 (VGLUT1) and VGLUT2 in the trigeminal ganglion (TG) and the dental pulp before and after inducing pulpal inflammation. Many TRPM8+ neurons in the TG and axons in the dental pulp expressed VGLUT2, while none expressed VGLUT1. TRPM8+ axons were dense in the pulp horn and peripheral pulp and also frequently observed in the dentinal tubules. Following pulpal inflammation, the proportion of VGLUT2+ and of VGLUT2+/TRPM8+ neurons increased significantly, whereas that of TRPM8+ neurons remained unchanged. Our findings suggest the existence of VGLUT2 (but not VGLUT1)-mediated glutamate signaling in TRPM8+ neurons possibly underlying the cold-induced acute pain and hypersensitivity to cold following pulpal inflammation.
authors.affiliation: Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu 700-412, South Korea.
authors.forename: Y S
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu 700-412, South Korea.
authors.forename: T H
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Neurobiology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: D D
authors.initials: DD
authors.lastname: McKemy
authors.affiliation: Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu 700-412, South Korea. Electronic address: ycbae@knu.ac.kr.
authors.forename: Y C
authors.initials: YC
authors.lastname: Bae
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011671:Pulpitis / Q000378:metabolism* / Q000473:pathology*; D011984:Sensory Receptor Cells / Q000378:metabolism*; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*; D014276:Trigeminal Nerve / Q000473:pathology*; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism*
chemical_list: D050053:TRPM Cation Channels; C492297:TRPM8 protein, mouse; D050599:Vesicular Glutamate Transport Protein 2; D049452:Green Fluorescent Proteins
keywords: TRPM8; cold pain; dental pulp; inflammation; vesicular glutamate transporter