Document Detail


Systemic pre-treatment with a group II mGlu agonist, LY379268, reduces hyperalgesia in vivo.
MedLine Citation:
PMID:  11877334     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. Previous studies investigating the role of metabotropic glutamate (mGlu) receptors in nociceptive processing have been hampered by the lack of systemically active, selective, ligands. This study investigates the possible analgesic and/or anti-hyperalgesic properties of the most potent compound to date that has systemic agonist activity at group II mGlu receptors, LY379268. 2. In testing the drug in rats as an analgesic to acute noxious stimuli, LY379268 (in doses up to 3 mg kg(-1) i.p.) did not affect withdrawal latencies to either mechanical or thermal stimulation. 3. However, when a 3 mg kg(-1) dose was given prior to an intraplantar injection of carrageenan, the inflammatory hyperalgesia that developed was significantly delayed compared to saline pre-treated controls, without affecting the inflammation of the paw. A similar dose of the mGlu-inactive enantiomer, LY379267, was not anti-hyperalgesic. 4. In a model of mouse tail withdrawal to warm water, LY379268 (12 mg kg(-1) i.p.), given before a subcutaneous tail injection of capsaicin, reduced the subsequent neurogenic hyperalgesia. 5. Rota-rod testing showed that the drug did not produce a motor impairment in rats at antihyperalgesic doses. 6. The results indicate that systemic activation of this group of mGlu receptors reduces both inflammatory and neurogenic thermal hyperalgesia.
Authors:
E F Sharpe; A E Kingston; D Lodge; J A Monn; P M Headley
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  135     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2002 Mar 
Date Detail:
Created Date:  2002-03-05     Completed Date:  2002-08-16     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1255-62     Citation Subset:  IM    
Affiliation:
Department of Physiology, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK.
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MeSH Terms
Descriptor/Qualifier:
Amino Acids / therapeutic use*
Animals
Bicyclo Compounds, Heterocyclic / therapeutic use*
Carrageenan / toxicity
Hindlimb
Hyperalgesia / chemically induced,  drug therapy*,  physiopathology
Inflammation / chemically induced,  drug therapy*,  physiopathology
Injections, Intraperitoneal
Male
Mice
Mice, Inbred C57BL
Pain Threshold / drug effects,  physiology
Rats
Rats, Sprague-Dawley
Receptors, Metabotropic Glutamate / agonists*
Tail
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Bicyclo Compounds, Heterocyclic; 0/LY 379268; 0/Receptors, Metabotropic Glutamate; 9000-07-1/Carrageenan
Comments/Corrections

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