Abstract
The metabotropic glutamate receptors (mGluRs) are found throughout the central nervous system, where they modulate neuronal excitability and synaptic transmission. Here we report the presence of phospholipase C-coupled group I mGluRs (mGluR1 and mGluR5) outside the central nervous system on peripheral unmyelinated sensory afferents. Given their localization on predominantly nociceptive afferents, we investigated whether these receptors modulate nociceptive signaling, and found that agonist-induced activation of peripheral group I mGluRs leads to increased sensitivity to noxious heat, a phenomenon termed thermal hyperalgesia. Furthermore, group I mGluR antagonists not only prevent, but also attenuate established formalin-induced pain. Taken together, these results suggest that peripheral mGluRs mediate a component of hyperalgesia and may be therapeutically targeted to prevent and treat inflammatory pain.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Chromones / pharmacology
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Excitatory Amino Acid Antagonists / pharmacology
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Glycine / analogs & derivatives
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Glycine / pharmacology
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Hindlimb
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Hot Temperature
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Immunohistochemistry
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Inflammation / physiopathology
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Male
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Mice
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Mice, Inbred C57BL
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Neurons, Afferent / drug effects
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Neurons, Afferent / metabolism*
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Neurons, Afferent / ultrastructure
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Pain / chemically induced
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Pain / physiopathology*
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Pain Measurement
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Pyridines / pharmacology
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Receptors, Metabotropic Glutamate / antagonists & inhibitors
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Receptors, Metabotropic Glutamate / metabolism*
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Valine / analogs & derivatives*
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Valine / pharmacology
Substances
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7-(hydroxyimino)cyclopropan(b)chromen-1a-carbxoylic acid ethyl ester
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Chromones
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Excitatory Amino Acid Antagonists
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Pyridines
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Receptors, Metabotropic Glutamate
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2-amino-5-phosphopentanoic acid
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6-methyl-2-(phenylethynyl)pyridine
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Valine
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Glycine