TY - JOUR
T1 - Peripheral group II metabotropic glutamate receptors (mGluR2/3) regulate prostaglandin E2-mediated sensitization of capsaicin responses and thermal nociception
AU - Yang, Dongni
AU - Gereau IV, Robert W.
PY - 2002/8/1
Y1 - 2002/8/1
N2 - Previous studies have shown that group II metabotropic glutamate receptors (mGluRs) are present on the peripheral terminals of primary sensory neurons, suggesting that they might be involved in nociception. In this study, we investigated the modulation of nociception by peripheral group II mGluRs and the molecular basis of this modulation. Subcutaneous injection of a group II mGluR agonist, 2R,4R 4-aminopyrrolidine-2,4-dicarboxylate (APDC), did not alter thermal sensitivity but blocked prostaglandin E2 (PGE2)-induced thermal hyperalgesia. This effect was blocked by (2s)-2-amino-2-[(1s,2s)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid, a selective group II mGluR antagonist. In cultured primary sensory neurons, APDC blocked PGE2-induced potentiation of capsaicin responses, which was abolished when neurons were pretreated with pertussis toxin. Similar potentiating effects induced by forskolin but not 8-bromo-cAMP were also blocked by the activation of group II mGluRs. These results indicate that peripheral group II mGluRs act via inhibition of adenylyl cyclase to reverse the sensitization of capsaicin receptors and the thermal hyperalgesia induced by PGE2, and suggest that peripheral group II mGluRs might be targeted for therapeutic intervention in inflammatory pain states.
AB - Previous studies have shown that group II metabotropic glutamate receptors (mGluRs) are present on the peripheral terminals of primary sensory neurons, suggesting that they might be involved in nociception. In this study, we investigated the modulation of nociception by peripheral group II mGluRs and the molecular basis of this modulation. Subcutaneous injection of a group II mGluR agonist, 2R,4R 4-aminopyrrolidine-2,4-dicarboxylate (APDC), did not alter thermal sensitivity but blocked prostaglandin E2 (PGE2)-induced thermal hyperalgesia. This effect was blocked by (2s)-2-amino-2-[(1s,2s)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid, a selective group II mGluR antagonist. In cultured primary sensory neurons, APDC blocked PGE2-induced potentiation of capsaicin responses, which was abolished when neurons were pretreated with pertussis toxin. Similar potentiating effects induced by forskolin but not 8-bromo-cAMP were also blocked by the activation of group II mGluRs. These results indicate that peripheral group II mGluRs act via inhibition of adenylyl cyclase to reverse the sensitization of capsaicin receptors and the thermal hyperalgesia induced by PGE2, and suggest that peripheral group II mGluRs might be targeted for therapeutic intervention in inflammatory pain states.
KW - Capsaicin
KW - DRG
KW - Inflammation
KW - PGE
KW - PKA
KW - Pain
KW - Phosphorylation
KW - Prostanoid
KW - VR1
KW - cAMP
KW - mGluR
UR - http://www.scopus.com/inward/record.url?scp=0036703485&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.22-15-06388.2002
DO - 10.1523/jneurosci.22-15-06388.2002
M3 - Article
C2 - 12151517
AN - SCOPUS:0036703485
VL - 22
SP - 6388
EP - 6393
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 15
ER -