Biphasic modulation of noxious heat sensitivity in sensory neurons by peripheral metabotropic glutamate receptors

Release of glutamate during inflammation and injury changes sensitivity and transmission efficiency of noxious sensory information via glutamate receptors. We found that activation of metabotropic glutamate receptor type 5 (mGluR5) transiently increased, and then subsequently decreased, noxious heat sensitivity. Similarly, mGluR5 activation in cultured sensory neurons potentiated intracellular calcium elevation mediated by transient receptor potential channel, subfamily V, member 1 (TRPV1), a noxious heat receptor; subsequent cessation of mGluR5 activation depressed intracellular calcium levels. The underlying mechanisms were potentiation of TRPV1 current in the presence of mGluR5 ligands and persistent inhibition of voltage-gated calcium channels (VGCC), even after mGluR5 ligand washout. Thus, mGluR5 biphasically modulates TRPV1-mediated cellular responses in sensory neurons, which contributes to heat hyper- and hypoalgesia. These phenomena may contribute to changes in noxious heat sensitivity during inflammation and healing.