RT Journal Article
SR Electronic
T1 Group I Metabotropic Glutamate Receptor Antagonists Block Secondary Thermal Hyperalgesia in Rats with Knee Joint Inflammation
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 149
OP 156
DO 10.1124/jpet.300.1.149
VO 300
IS 1
A1 Liping Zhang
A1 Ying Lu
A1 Ying Chen
A1 Karin N. Westlund
YR 2002
UL http://jpet.aspetjournals.org/content/300/1/149.abstract
AB Activation of ionotropic glutamate receptors has been shown previously to be essential for the development of secondary thermal hyperalgesia. The present study assessed involvement of group I metabotropic glutamate receptors (mGlu) in both the induction and maintenance phases of secondary thermal hyperalgesia initiated by knee joint inflammation in rats. The dose dependence of each drug in antagonism of thermal hypersensitivity was demonstrated in pre- and post-treatment paradigms. Knee joint inflammation was induced by injection of kaolin and carrageenan. Four hours later the paw withdrawal latencies were significantly shorter than baseline values. Rats were pretreated by spinal microdialysis infusion of group I mGlu receptor antagonists, LY393053 [(±)-2-amino-2-(3-cis andtrans-carboxycyclobutyl-3-(9-thioxanthyl)propionic acid], LY367385 [(S)-(+)-α-amino-4-carboxy-2-methylbenzeneacetic acid], or AIDA [(R,S)-1-aminoindan-1,5-dicarboxylic acid/UPF 523] before knee joint injection.The paw withdrawal latencies measured 4 h after the injection were significantly longer in the presence of group I mGlu receptor antagonists than those of the artificial cerebrospinal fluid-treated arthritic control group. Post-treatment with the group I mGlu receptor antagonists LY367385 and AIDA allowed significant recovery of the paw withdrawal latencies after the onset of the knee joint inflammation. The knee joint inflammation itself was not affected by either treatment. The results of the present study indicate that secondary thermal hyperalgesia can be effectively attenuated during both the development and maintenance phases of acute knee joint inflammation by spinal application of specific group I mGlu receptor antagonists. NMDA N-methyl-d-aspartatemGlumetabotropic glutamateLY393053(+)-2-amino-2-(3-cis andtrans-carboxycyclobutyl-3-(9-thioxanthyl)propionic acidLY367385(S)-(+)-α-amino-4-carboxy-2-methylbenzeneacetic acidAIDA(R,S)-1-aminoindan-1,5-dicarboxylic acid/UPF 523AMPAα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acidaCSFartificial cerebrospinal fluid