Presynaptic low- and high-affinity kainate receptors in nociceptive spinal afferents.
Presynaptic ionotropic glutamate receptors are increasingly attributed a role in the modulation of sensory input at the first synapse of dorsal root ganglion (DRG) neurons in the spinal dorsal horn. Central terminals of DRG neurons express AMPA and NMDA receptors whose activation modulates the release of glutamate, the main transmitter at these synapses. Previous work, with an antibody that recognizes all low-affinity kainate receptor subunits (GluR5, 6, 7), provided microscopic evidence of presynaptic kainate receptors in unidentified primary afferent terminals in superficial laminae of the spinal dorsal horn (Hwang SJ, Pagliardini S, Rustioni A, Valtschanoff JG. Presynaptic kainate receptors in primary afferents to the superficial laminae of the rat spinal cord. J Comp Neurol 2001; 436: pp. 275-289). We show here that, although all such subunits may be expressed in these terminals, GluR5 is the subunit most readily detectable at presynaptic sites in sections processed for immunocytochemistry. We also show that the high-affinity kainate receptor subunits KA1 and KA2 are expressed in central terminals of DRG neurons and are co-expressed with low-affinity receptor subunits in the same terminals. Quantitative data show that kainate-expressing DRG neurons are about six times more likely to express the P2X(3) subunit of the purinergic receptor than to express substance P. Thus, nociceptive afferents that express presynaptic kainate receptors are predominantly non-peptidergic, suggesting a role for these receptors in the modulation of neuropathic rather than inflammatory pain.
Lucifora
Simona
S
Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA Department of Physiological Sciences, University of Catania, Italy Institute of Anatomy and Cell Biology I, University of Freiburg, Albertstrasse 17, D-79104 Freiburg, Germany.
Willcockson
Helen H
HH
Lu
Chun-Rong
CR
Darstein
Melanie
M
Phend
Kris D
KD
Valtschanoff
Juli G
JG
Rustioni
Aldo
A
D000344:Afferent Pathways / Q000378:metabolism*; D000818:Animals; D005727:Ganglia, Spinal / Q000378:metabolism*; D009619:Nociceptors / Q000378:metabolism*; D020671:Posterior Horn Cells / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018092:Kainic Acid Receptors / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism; D014018:Tissue Distribution
D018092:Kainic Acid Receptors; D017661:Receptors, Presynaptic