Damaged tissues release
glutamate and other chemical mediators for several hours. These chemical mediators contribute to modulation of
pruritus and
pain. Herein, we investigated the effects of long-term activation of excitatory
glutamate receptors on functional expression of transient receptor potential vaniloid type 1 (TRPV1) in dorsal root ganglion (DRG) neurons and then on thermal
pain behavior. In order to detect the TRPV1-mediated responses in cultured DRG neurons, we monitored intracellular
calcium responses to
capsaicin, a TRPV1 agonist, with
Fura-2. Long-term (4 h) treatment with
glutamate receptor agonists (glutamate,
quisqualate or
DHPG) increased the proportion of neurons responding to
capsaicin through activation of
metabotropic glutamate receptor mGluR1, and only partially through the activation of mGluR5; engagement of these receptors was evident in neurons responding to allylisothiocyanate (
AITC), a transient receptor potential
ankyrin type 1 (TRPA1) agonist. Increase in the proportion was suppressed by
phospholipase C (PLC),
protein kinase C,
mitogen/
extracellular signal-regulated kinase,
p38 mitogen-activated protein kinase or transcription inhibitors. Whole-cell recording was performed to record TRPV1-mediated membrane current; TRPV1 current density significantly increased in the
AITC-sensitive neurons after the
quisqualate treatment. To elucidate the physiological significance of this phenomenon, a hot plate test was performed. Intraplantar injection of
quisqualate or
DHPG induced heat
hyperalgesia that lasted for 4 h post injection. This chronic
hyperalgesia was attenuated by treatment with either
mGluR1 or mGluR5 antagonists. These results suggest that long-term activation of
mGluR1/5 by peripherally released
glutamate may increase the number of neurons expressing functional TRPV1 in DRG, which may be strongly associated with chronic
hyperalgesia.