Activation of brainstem metabotropic glutamate receptors inhibits spinal nociception in adult rats.
In this study, we provide evidence that focal electrical stimulation applied to the rostroventral medulla (RVM) at a high frequency (100 Hz) produced inhibition of the spinal nociceptive tail-flick (TF) reflex in lightly anesthetized adult rats. Chemical activation of metabotropic glutamate (mGlu) receptors by local injection of (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (tACPD), the mGlu receptor agonist, produced a dose-related inhibition of the TF reflex. Injection of the Group II mGlu receptor agonist (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl) glycine (DCGIV) produced strong inhibition, while injection of the Group III mGlu receptor agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4) did not produce any effect. (RS)-alpha-Methyl-4-carboxyphenylglycine (MCPG), a selective mGlu receptor antagonist, but not naloxone reversed the inhibitory effects of DCGIV. Our results provide physiological evidence in vivo that activation of Group II mGlu receptors in the brainstem is antinociceptive and drugs targetting these receptors may help to control pain in humans.
Department of Anesthesiology, Washington University Pain Center, Washington University Medical Center, Washington University in St. Louis, Campus Box 8054, St. Louis, MO 63110, USA.
Susan J
SJ
Kim
Amelita A
AA
Calejesan
Min
M
Zhuo
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001933:Brain Stem / Q000502:physiology*; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology; D008845:Microinjections; D010487:Periaqueductal Gray / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D012018:Reflex / Q000502:physiology; D013116:Spinal Cord / Q000502:physiology*; D013268:Stimulation, Chemical
D000700:Analgesics; D018690:Excitatory Amino Acid Agonists; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane