Evaluation of phenoxybenzamine in the CFA model of pain following gene expression studies and connectivity mapping

摘要: We have previously used the rat 4 day Complete Freund's Adjuvant (CFA) model to screen compounds with potential reduce osteoarthritic pain. The aim of this study was identify genes altered in pain and use information infer analgesic based on their own gene expression profiles using Connectivity Map approach. Using microarrays, we identified differentially expressed L4 L5 dorsal root ganglia (DRG) from rats that had received intraplantar CFA for days compared matched, untreated control animals. Analysis these data indicated two groups were distinguishable by differences important immune responses, nerve growth regeneration. This list defined a "CFA signature". approach pharmacologic agents Broad Institute Build02 database signatures inversely related ('negatively connected') our signature. To test predictive nature methodology, tested phenoxybenzamine (an alpha adrenergic receptor antagonist) - one most negatively connected activity model. Our results indicate at 10 mg/kg, demonstrated analgesia comparable Naproxen Evaluation phenoxybenzamine-induced current lends support utility identifying properties