Linked Life Data

19766393

Source:http://linkedlifedata.com/resource/pubmed/id/19766393

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2009-11-25
pubmed:abstractText
The analgesic mechanism underlying the efficacy of topical diclofenac in the treatment of musculoskeletal pain is incompletely understood. The present study investigated whether intramuscular injection of diclofenac (0.1mg/ml, approximately 340microM) could attenuate jaw-closer muscle nociceptor discharge and mechanical sensitization induced by activation of peripheral 5-hydroxytryptamine (serotonin) or excitatory amino acid receptors in anesthetized Sprague-Dawley rats. Diclofenac inhibited nociceptor discharge evoked by NMDA, but had no effect on nociceptor discharge evoked by 5-hydroxytryptamine or AMPA. Subsequent experiments revealed that diclofenac-mediated inhibition of NMDA-evoked nociceptor discharge was competitive. Intramuscular injection of 5-hydroxytryptamine, NMDA and AMPA also decreased nociceptor mechanical threshold, however, only the mechanical sensitization produced by NMDA was reversed by diclofenac. Co-administration of the proinflammatory prostaglandin PGE(2) did not alter the ability of diclofenac to significantly attenuate NMDA-evoked nociceptor discharge or NMDA-induced mechanical sensitization. Intramuscular injection of either diclofenac or the competitive NMDA receptor antagonist DL-2-amino-5-phosphonovalerate (50mM) alone could elevate nociceptor mechanical threshold for a 30min period post-injection. The present study indicates that in vivo, diclofenac can exert a selective, competitive inhibition of peripheral NMDA receptors at muscle concentrations achievable after topical administration of diclofenac containing preparations. This property may contribute to the analgesic effect of topical diclofenac when used for muscle pain.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1872-6623
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
147
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
36-45
pubmed:meshHeading
pubmed-meshheading:19766393-2-Amino-5-phosphonovalerate, pubmed-meshheading:19766393-Anesthetics, Local, pubmed-meshheading:19766393-Animals, pubmed-meshheading:19766393-Biophysics, pubmed-meshheading:19766393-Dinoprostone, pubmed-meshheading:19766393-Disease Models, Animal, pubmed-meshheading:19766393-Dose-Response Relationship, Drug, pubmed-meshheading:19766393-Electric Stimulation, pubmed-meshheading:19766393-Evoked Potentials, pubmed-meshheading:19766393-Excitatory Amino Acid Antagonists, pubmed-meshheading:19766393-Injections, Intramuscular, pubmed-meshheading:19766393-Isoquinolines, pubmed-meshheading:19766393-Male, pubmed-meshheading:19766393-Musculoskeletal Diseases, pubmed-meshheading:19766393-N-Methylaspartate, pubmed-meshheading:19766393-Pain, pubmed-meshheading:19766393-Physical Stimulation, pubmed-meshheading:19766393-Rats, pubmed-meshheading:19766393-Rats, Sprague-Dawley, pubmed-meshheading:19766393-Receptors, N-Methyl-D-Aspartate, pubmed-meshheading:19766393-Serotonin, pubmed-meshheading:19766393-Time Factors, pubmed-meshheading:19766393-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
pubmed:year
2009
pubmed:articleTitle
The analgesic action of topical diclofenac may be mediated through peripheral NMDA receptor antagonism.
pubmed:affiliation
Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't