AIDA reduces glutamate release and attenuates mechanical allodynia after spinal cord injury.
Spinal cord injury (SCI) leads to an increase in extracellular excitatory amino acid (EAA) concentrations, resulting in glutamate receptor-mediated excitotoxicity and central sensitization. To test contributions of group I metabotropic glutamate receptors (mGluRs) in SCI induced release of glutamate and in behavioral outcomes of central sensitization following injury, we administered 1-aminoindan-1,5-dicarboxylic acid (AIDA; 0.1 nmol intraspinally), a potent group I mGluR antagonist, to rats immediately after spinal cord contusion injury. EAAs were collected by microdialysis and quantified using HPLC. AIDA significantly decreased extracellular glutamate but not aspartate concentrations and significantly attenuated the development of mechanical but not thermal allodynia. These results suggest mGluRs play an important role in injury-induced EAA release and in central sensitization following SCI.
Mills
C D
CD
The Department of Anatomy and Neurosciences, The University of Texas Medical Branch at Galveston, 77555-1069, USA.
Xu
G Y
GY
Johnson
K M
KM
McAdoo
D J
DJ
Hulsebosch
C E
CE
D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D007189:Indans / Q000494:pharmacology*; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000150:complications* / Q000378:metabolism*
C095756:1-aminoindan-1,5-dicarboxylic acid; D018691:Excitatory Amino Acid Antagonists; D007189:Indans; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D018698:Glutamic Acid