Abstract
This study examines key elements of glutamatergic transmission within sensory ganglia of the rat. We show that the soma of primary sensory neurons release glutamate when depolarized. Using acute dissociated mixed neuronal/glia cultures of dorsal root ganglia (DRG) or trigeminal ganglia and a colorimetric assay, we show that when glutamate uptake by satellite glial cells (SGCs) is inhibited, KCl stimulation leads to simultaneous increase of glutamate in the culture medium. With calcium imaging we see that the soma of primary sensory neurons and SGCs respond to AMPA, NMDA, kainate and mGluR agonists, and selective antagonists block this response. Using whole cell patch-clamp technique, inward currents were recorded from small diameter (<30 µm) DRG neurons from intact DRGs (ex-vivo whole ganglion preparation) in response to local application of the above glutamate receptor agonists. Following a chronic constriction injury (CCI) of either the inferior orbital nerve or the sciatic nerve, glutamate expression increases in the trigeminal ganglia and DRG respectively. This increase occurs in neurons of all diameters and is present in the somata of neurons with injured axons as well as in somata of neighboring uninjured neurons. These data provides additional evidence that glutamate can be released within the sensory ganglion, and that the somata of primary sensory neurons as well as SGCs express functional glutamate receptors at their surface. These findings, together with our previous gene knockdown data, suggest that glutamatergic transmission within the ganglion could impact nociceptive threshold.
Highlights
Glutamate is the common excitatory neurotransmitter of the central and peripheral nervous systems and is found in both nociceptive as well as non-nociceptive sensory pathways [1,2,3,4]
We have indirect evidence for nonsynaptic transmission from experiments in the trigeminal ganglion in which a glutamate-glutamine cycle enzyme or a glutamate uptake transporter were knocked-down using double stranded RNA [22,23]. These studies showed that the knockdown was confined to the local satellite glial cells (SGCs) and that pain behavior was consistently altered, which can be best explained by a change in intraganglionic glutamatergic transmission
Glutamate is Released from Mixed dorsal root ganglia (DRG) Cell Culture In this experiment, we asked two questions: whether neuronal stimulation can induce glutamate release from somas and whether blocking glutamate uptake will increase the extracellular concentration of glutamate
Summary
Glutamate is the common excitatory neurotransmitter of the central and peripheral nervous systems and is found in both nociceptive as well as non-nociceptive sensory pathways [1,2,3,4]. The possibility of targeting glutamatergic transmission in the peripheral nervous system has been suggested given that small diameter primary sensory neurons, many of which are nociceptive, express glutamate and glutamate receptors [5,6,7]. We have indirect evidence for nonsynaptic transmission from experiments in the trigeminal ganglion in which a glutamate-glutamine cycle enzyme or a glutamate uptake transporter were knocked-down using double stranded RNA [22,23] These studies showed that the knockdown was confined to the local satellite glial cells (SGCs) and that pain behavior was consistently altered, which can be best explained by a change in intraganglionic glutamatergic transmission
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