Role of group II and group III metabotropic glutamate receptors in spinal cord injury.
Spinal cord injury (SCI) produces an increase in extracellular excitatory amino acid (EAA) concentrations that results in glutamate receptor-mediated excitotoxic events. An important class of these receptors is the metabotropic glutamate receptors (mGluRs). mGluRs can activate a number of intracellular pathways that increase neuronal excitability and modulate neurotransmission. Group I mGluRs are known to modulate EAA release and the development of chronic central pain (CCP) following SCI; however, the role of group II and III mGluRs remains unclear. To begin evaluating group II and III mGluRs in SCI, we administered the specific agonists for group II, APDC, or group III, L-AP4, by interspinal injection immediately following SCI. Contusion injury was produced at spinal segment T10 with a New York University impactor (12.5-mm drop, 10-g rod 2 mm in diameter) in 30 adult male Sprague-Dawley rats (175-200 g). Evoked and spontaneous behavioral measures of CCP, locomotor recovery, changes in mGluR expression, and amount of spared tissue were examined. Neither APDC nor L-AP4 affected locomotor recovery or the development of thermal hyperalgesia; however, L-AP4 and APDC attenuated changes in mechanical thresholds and changes in exploratory behavior indicative of CCP. APDC- and L-AP4-treated groups had higher expression levels of mGluR2/3 at the epicenter of injury on post contusion day 28; however, there was no difference in the amount of spared tissue between treatment groups. These results demonstrate that treatment with agonists to group II and III mGluRs following SCI affects mechanical responses, exploratory behavior, and mGluR2/3 expression without affecting the amount of tissue spared, suggesting that the level of mGluR expression after SCI may modulate nociceptive responses.
Mills
Charles D
CD
Department of Anatomy and Neurosciences, The University of Texas Medical Branch at Galveston, Galveston, Texas 77555-1043, USA.
Johnson
Kathia M
KM
Hulsebosch
Claire E
CE
D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal; D002908:Chronic Disease; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005106:Exploratory Behavior; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology; D008297:Male; D009043:Motor Activity; D010147:Pain Measurement; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D020127:Recovery of Function; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D014949:Wounds, Nonpenetrating
C097299:4-aminopyrrolidine-2,4-dicarboxylic acid; D000613:Aminobutyrates; D018690:Excitatory Amino Acid Agonists; D018094:Receptors, Metabotropic Glutamate; D011392:Proline; C012729:2-amino-4-phosphonobutyric acid