Membrane-delimited coupling of TRPV1 and mGluR5 on presynaptic terminals of nociceptive neurons.
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.
Kim
Yong Ho
YH
Dental Research Institute, Department of Physiology School of Dentistry, Seoul National University, Republic of Korea.
Park
Chul-Kyu
CK
Back
Seung Keun
SK
Lee
C Justin
CJ
Hwang
Se Jin
SJ
Bae
Yong Chul
YC
Na
Heung Sik
HS
Kim
Joong Soo
JS
Jung
Sung Jun
SJ
Oh
Seog Bae
SB
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*
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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