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Peripheral group I metabotropic glutamate receptors modulate nociception in mice

Nature Neuroscience volume 4, pages 417–423 (2001)Cite this article

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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Figure 1: Localization of mGluR5 and mGluR1a on unmyelinated peripheral afferents.
Figure 2: The group I mGluR agonist, RS-DHPG, enhances thermal sensitivity.
Figure 3: DHPG-induced thermal hypersensitivity is attenuated by pretreatment with mGluR5 and mGluR1 antagonists.
Figure 4: APV and MPPG did not reduce DHPG-induced thermal hypersensitivity.
Figure 5: MPEP and CPCCOEt blocked glutamate-induced thermal hypersensitivity.
Figure 6: Pre-treatment with MPEP or CPCCOEt diminished the second phase of the formalin test.
Figure 7: CPCCOEt and MPEP reduced the formalin test second phase when administered after the first phase.

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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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  1. G. Bhave and F. Karim: The first two authors contributed equally to this work

Authors and Affiliations

  1. Division of Neuroscience, Baylor College of Medicine, 1 Baylor Plaza, Room S636, Houston, 77030, Texas, USA

    G. Bhave, F. Karim & R. W. Gereau IV

  2. Department of Anatomy and Neurosciences, Marine Biomedical Institute, 301 University Boulevard, Galveston, 77555, Texas, USA

    S. M. Carlton

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Correspondence to R. W. Gereau IV.

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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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