title: Membrane-delimited coupling of TRPV1 and mGluR5 on presynaptic terminals of nociceptive neurons.
abstract: Transient receptor potential vanilloid subtype 1 (TRPV1) and metabotropic glutamate receptor 5 (mGluR5) located on peripheral sensory terminals have been shown to play critical roles in the transduction and modulation of pain sensation. To date, however, very little is known regarding the significance of functional expression of mGluR5 and TRPV1 on the central terminals of sensory neurons in the dorsal horn of the spinal cord. Here we show that TRPV1 on central presynaptic terminals is coupled to mGluR5 in a membrane-delimited manner, thereby contributing to the modulation of nociceptive synaptic transmission in the substantia gelatinosa neurons of the spinal cord. Further, our results demonstrate that TRPV1 is involved in the pain behaviors induced by spinal mGluR5 activation, and diacylglycerol produced by the activation of mGluR5 mediates functional coupling of mGluR5 and TRPV1 on the presynaptic terminals. Thus, mGluR5-TRPV1 coupling on the central presynaptic terminals of nociceptive neurons may be an important mechanism underlying central sensitization under pathological pain conditions.
authors.affiliation: Dental Research Institute, Department of Physiology School of Dentistry, Seoul National University, Republic of Korea.
authors.forename: Yong Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Chul-Kyu
authors.initials: CK
authors.lastname: Park
authors.forename: Seung Keun
authors.initials: SK
authors.lastname: Back
authors.forename: C Justin
authors.initials: CJ
authors.lastname: Lee
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Yong Chul
authors.initials: YC
authors.lastname: Bae
authors.forename: Heung Sik
authors.initials: HS
authors.lastname: Na
authors.forename: Joong Soo
authors.initials: JS
authors.lastname: Kim
authors.forename: Sung Jun
authors.initials: SJ
authors.lastname: Jung
authors.forename: Seog Bae
authors.initials: SB
authors.lastname: Oh
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D004075:Diglycerides / Q000378:metabolism; D005727:Ganglia, Spinal / Q000503:physiopathology; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology; D010146:Pain / Q000503:physiopathology*; D020671:Posterior Horn Cells / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D013376:Substantia Gelatinosa / Q000503:physiopathology; D009435:Synaptic Transmission / Q000502:physiology; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D004075:Diglycerides; C578935:GRM5 protein, human; C578936:Grm5 protein, mouse; C578937:Grm5 protein, rat; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D050916:TRPV Cation Channels; D002118:Calcium
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