The glutamatergic nature of TRPV1-expressing neurons in the spinal dorsal horn.
The transient receptor potential vanilloid receptor 1 (TRPV1) is expressed on primary afferent terminals and spinal dorsal horn neurons. However, the neurochemical phenotypes and functions of TRPV1-expressing post-synaptic neurons in the spinal cord are not clear. In this study, we tested the hypothesis that TRPV1-expressing dorsal horn neurons are glutamatergic. Immunocytochemical labeling revealed that TRPV1 and vesicular glutamate transporter-2 were colocalized in dorsal horn neurons and their terminals in the rat spinal cord. Resiniferatoxin (RTX) treatment or dorsal rhizotomy ablated TRPV1-expressing primary afferents but did not affect TRPV1- and vesicular glutamate transporter-2-expressing dorsal horn neurons. Capsaicin significantly increased the frequency of glutamatergic spontaneous excitatory post-synaptic currents and miniature excitatory post-synaptic currents in almost all the lamina II neurons tested in control rats. In RTX-treated or dorsal rhizotomized rats, capsaicin still increased the frequency of spontaneous excitatory post-synaptic currents and miniature excitatory post-synaptic currents in the majority of neurons examined, and this effect was abolished by a TRPV1 blocker or by non-NMDA receptor antagonist. In RTX-treated or in dorsal rhizotomized rats, capsaicin also produced an inward current in a subpopulation of lamina II neurons. However, capsaicin had no effect on GABAergic and glycinergic spontaneous inhibitory post-synaptic currents of lamina II neurons in RTX-treated or dorsal rhizotomized rats. Collectively, our study provides new histological and functional evidence that TRPV1-expressing dorsal horn neurons in the spinal cord are glutamatergic and that they mediate excitatory synaptic transmission. This finding is important to our understanding of the circuitry and phenotypes of intrinsic dorsal horn neurons in the spinal cord.
Zhou
Hong-Yi
HY
Department of Anesthesiology and Pain Medicine, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA.
Chen
Shao-Rui
SR
Chen
Hong
H
Pan
Hui-Lin
HL
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005727:Ganglia, Spinal / Q000166:cytology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D066298:In Vitro Techniques; D037102:Lectins / Q000378:metabolism; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019051:Rhizotomy / Q000379:methods; D013116:Spinal Cord / Q000166:cytology*; D050916:TRPV Cation Channels / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D053675:Versicans; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism
D004224:Diterpenes; D018691:Excitatory Amino Acid Antagonists; D006023:Glycoproteins; D037102:Lectins; D018721:Muscarinic Agonists; C493475:Slc17a6 protein, rat; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C508324:Vcan protein, rat; D050599:Vesicular Glutamate Transport Protein 2; D053675:Versicans; D018698:Glutamic Acid; D010095:Oxotremorine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C024353:resiniferatoxin; D002211:Capsaicin