Abstract
Glutamate is the major excitatory transmitter in the spinal cord dorsal horn. At postsynaptic sites, subtypes of glutamate receptors are important for mediating sensory synaptic responses. While AMPA and NMDA receptors are likely expressed in all sensory synapses, kainate(KA) receptors are expressed mainly in synapses receiving high-threshold sensory inputs. In addition to its postsynaptic role, presynaptic KA receptors are important for regulation of both excitatory and inhibitory transmission within the dorsal horn. In the spinal cord dorsal horn, excitatory sensory fibers often terminate adjacent to sites of GABA and glycine release. Glutamate released from sensory fibers caused a KA and GABAB receptor-dependent suppression of inhibitory transmission in spinal slices, providing evidence for a new role of KA receptors in regulating sensory transmission. Genetic studies using selective KA subtype receptor knockout mice found that KA receptors are important for persistent inflammatory pain as well as emotional responses to pain.
This is a preview of subscription content, log in via an institution to check access.
Preview
Unable to display preview. Download preview PDF.
General Citations
Bleakman D, Lodge D. 1998. Neuropharmacology of AMPA and KA receptors. Neuropharmacology, 37: 1187–1204.
Bleakman D. 1999. KA receptor pharmacology and physiology. Cell Mol Life Sci, 56: 558–566.
Frerking M, Nicoll R A. 2000. Synaptic KA receptors. Curr Opin Neurobiol, 10: 342–351.
Lerma J. 2003. Roles and rules of KA receptors in synaptic transmission. Nat Rev Neurosci, 4: 481–495.
Zhuo M. 2004. Central plasticity in pathological pain. Novartis Found Symp, 261: 132–145. (discussion 145–154)
Huettner J E, Kerchner G A, Zhuo M. 2002. Glutamate and the presynaptic control of spinal sensory transmission. Neuroscientist, 8: 89–92.
Discovery Citations
Youn D H, et al. 2005. Altered long-term synaptic plasticity and KA-induced Ca(2+) transients in the substantia gelatinosa neurons in GLU(K6)-deficient mice. Brain Res Mol Brain Res, 142:9–18.
Kerchner G A, Wilding T J, Huettner J E, Zhuo M. 2002. KA receptor subunits underlying presynaptic regulation of transmitter release in the dorsal horn. J Neurosci, 22: 8010–8017.
Kerchner G A, Wilding T J, Li P, Zhuo M, Huettner J E. 2001. Presynaptic KA receptors regulate spinal sensory transmission. J Neurosci, 21: 59–66.
Kerchner G A, Wang G D, Qiu C S, Huettner J E, Zhuo M. 2001. Direct presynaptic regulation of GABA/glycine release by KA receptors in the dorsal horn: an ionotropic mechanism. Neuron, 32: 477–488.
Wu L J, Zhao M G, Toyoda H, Ko S, Zhuo M. 2005. KA receptor-mediated synaptic transmission in the adult anterior cingulate cortex. J Neurophysiol, 94: 1805–1813.
Dominguez E, et al. 2005. Two prodrugs of potent and selective GluR5 KA receptor antagonists actives in three animal models of pain. J Med Chem, 48: 4200–4203.
Lu C R, et al. 2005. Ionotropic glutamate receptors are expressed in GABAergic terminals in the rat superficial dorsal horn. J Comp Neurol, 486: 169–178.
Ko S, Zhao M G, Toyoda H, Qiu C S, Zhuo M. 2005. Altered behavioral responses to noxious stimuli and fear in glutamate receptor 5 (GluR5)-or GluR6-deficient mice. J Neurosci, 25: 977–984.
MacDermott A B. 2001. Glutamate and GABA: a painful combination. Neuron, 32: 376–378.
Sailer A, et al. 1999. Generation and analysis of GluR5(Q636R) KA receptor mutant mice. J Neurosci, 19: 8757–8764.
Li P,et al. 1999. KA-receptor-mediated sensory synaptic transmission in mammalian spinal cord. Nature, 397: 161–164.
Agrawal S G, Evans R H. 1986. The primary afferent depolarizing action of KA in the rat. Br J Pharmacol, 87: 345–355.
Ault B, Hildebrand L M. 1993. Activation of nociceptive reflexes by peripheral KA receptors. J Pharmacol Exp Ther, 265: 927–932.
Huettner J E. 1990. Glutamate receptor channels in rat DRG neurons: activation by KA and quisqualate and blockade of desensitization by Con A. Neuron, 5: 255–266.
Sato K, Kiyama H, Park H T, Tohyama M. 1993. AMPA, KA and NMDA receptors are expressed in the rat DRG neurones. Neuroreport, 4: 1263–1265.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2007 Higher Education Press
About this chapter
Cite this chapter
Zhuo, M. (2007). Glutamate Kainate Receptor in Pain Transmission and Modulation. In: Zhuo, M. (eds) Molecular Pain. Springer, New York, NY. https://doi.org/10.1007/978-0-387-75269-3_8
Download citation
DOI: https://doi.org/10.1007/978-0-387-75269-3_8
Publisher Name: Springer, New York, NY
Print ISBN: 978-0-387-75268-6
Online ISBN: 978-0-387-75269-3