Biphasic modulation by mGlu5 receptors of TRPV1‐mediated intracellular calcium elevation in sensory neurons contributes to heat sensitivity. (15th December 2014)

• Record Type: Journal Article
• Authors: Masuoka, T; Nakamura, T; Kudo, M; Yoshida, J; Takaoka, Y; Kato, N; Ishibashi, T; Imaizumi, N; Nishio, M
• Is Part Of: British journal of pharmacology. Volume 172:Number 4(2015:Feb.)
• Page Start: 1020
• Page End: 1033
• Publication Date: 2014-12-15
• Subjects: Pharmacology -- Periodicals; Chemotherapy -- Periodicals; Drug Therapy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/bph.12962
• Languages: English
• ISSNs: 0007-1188

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bph12962-sec-0001" sec-type="section"> <title>Background and Purpose</title> <p>Elevation of glutamate, an excitatory amino acid, during inflammation and injury plays a crucial role in the reception and transmission of sensory information via ionotropic and metabotropic receptors. This study aimed to investigate the mechanisms underlying the biphasic effects of metabotropic glutamate mGlu<sub>5</sub> receptor activation on responses to noxious heat.</p> </sec> <sec id="bph12962-sec-0002" sec-type="section"> <title>Experimental Approach</title> <p>We assessed the effects of intraplantar quisqualate, a non‐selective glutamate receptor agonist, on heat and mechanical pain behaviours in mice. In addition, the effects of quisqualate on the intracellular calcium response and on membrane currents mediated by TRPV1 channels, were examined in cultured dorsal root ganglion neurons from mice.</p> </sec> <sec id="bph12962-sec-0003" sec-type="section"> <title>Key Results</title> <p>Activation of mGlu<sub>5</sub> receptors in hind paw transiently increased, then decreased, the response to noxious heat. In sensory neurons, activation of mGlu<sub>5</sub> receptors potentiated TRPV1‐mediated intracellular calcium elevation, while terminating activation of mGlu<sub>5</sub> receptors depressed it. TRPV1‐induced currents were potentiated by activation of mGlu<sub>5</sub> receptors under voltage clamp conditions and these disappeared after washout. However, voltage‐gated calcium currents were inhibited by the mGlu<sub>5</sub> receptor agonist, even after washout.</p> </sec> <sec id="bph12962-sec-0004" sec-type="section"> <title>Conclusions and Implications</title> <p>These results suggest that, in sensory neurons, mGlu<sub>5</sub> receptors biphasically modulate TRPV1‐mediated intracellular calcium response via transient potentiation of TRPV1 channel‐induced currents and persistent inhibition of voltage‐gated calcium currents, contributing to heat hyper‐ and hypoalgesia.</p> </sec> </abstract>