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.
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Acknowledgements
The authors thank L.S. Baggett (Rice University, Department of Statistics) for assistance with the statistical analysis and B. Nadin for cell line immunocytochemistry. This work was supported by grants from the National Institutes of Health (MH60230 to R.W.G. and NS11255 and NS27910 to S.M.C.) and the Spinal Cord Research Foundation (R.W.G.). G.B. is a McNair Scholar of the Baylor College of Medicine Medical Scientist Training Program.
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Bhave, G., Karim, F., Carlton, S. et al. Peripheral group I metabotropic glutamate receptors modulate nociception in mice. Nat Neurosci 4, 417–423 (2001). https://doi.org/10.1038/86075
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DOI: https://doi.org/10.1038/86075
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