Antinociceptive effects and synergistic interaction with morphine of intrathecal metabotropic glutamate receptor 2/3 antagonist in the formalin test of rats.
Spinal metabotropic glutamate receptors (mGluRs) have been known to be involved in the modulation of nociception. While the antinociceptive effects of the mGluR1/5 have been demonstrated, the role of mGluR2/3 for nociception is less clear. This study investigated the effects of an intrathecal mGluR2/3 agonist, APDC, and a mGluR2/3 antagonist, LY341495, for inflammatory and acute pain in the formalin test and thermal stimulation test. We also examined their interaction with intrathecal morphine for the antinociceptive effect. APDC had little effect on the formalin-induced nociception. In contrast, LY341495 caused a dose-dependent suppression of the phase 2 flinching response to the formalin stimulus without affecting phase 1 flinching response. Furthermore, the suppression of pain behavior by LY341495 during phase 2 was reduced significantly by pretreatment with APDC. LY341495 and morphine also showed synergistic drug interaction for antinociception during phase 2 in the formalin test.
Yoon
Myung Ha
MH
Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, 8 Hakdong, Dongku, Gwangju 501-757, Korea. mhyoon@chonnam.ac.kr
Choi
Jeong ll
Jl
Bae
Hong Beom
HB
Kim
Seok Jai
SJ
Chung
Sung Tae
ST
Jeong
Seong Wook
SW
Chung
Sung Su
SS
Yoo
Kyung Yeon
KY
Jeong
Chang Yeong
CY
D000596:Amino Acids / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005557:Formaldehyde; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects*; D011392:Proline / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D012018:Reflex / Q000187:drug effects; D014966:Xanthenes / Q000494:pharmacology
C120942:1,4-diaminopyrrolidine-2,4-dicarboxylic acid; D000596:Amino Acids; D000700:Analgesics; D000701:Analgesics, Opioid; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D005557:Formaldehyde; D009020:Morphine; D011392:Proline