The α7 nicotinic receptor dual allosteric agonist and positive allosteric modulator GAT107 reverses nociception in mouse models of inflammatory and neuropathic pain
Bagdas D, Wilkerson J, Kulkarni A, Toma W, AlSharari S, Gul Z, Lichtman A, Papke R, Thakur G, Damaj M. The α7 nicotinic receptor dual allosteric agonist and positive allosteric modulator GAT107 reverses nociception in mouse models of inflammatory and neuropathic pain. British Journal Of Pharmacology 2016, 173: 2506-2520. PMID: 27243753, PMCID: PMC4959951, DOI: 10.1111/bph.13528.Peer-Reviewed Original ResearchConceptsPositive allosteric modulatorsNeuropathic painPain modelAntinociceptive effectSpinal cordTail flickChronic constriction injury (CCI) neuropathic pain modelAllosteric agonistDose-dependent antinociceptive effectΑ7 nicotinic ACh receptorsGlial fibrillary acidic proteinNeuropathic pain modelAstrocyte-specific glial fibrillary acidic proteinInflammatory pain modelAcetic acid injectionHot-plate assayEffective pharmacological strategiesNicotinic ACh receptorsNovel therapeutic approachesFibrillary acidic proteinDorsal hornFormalin testPain modulationSubchronic administrationLocus of actionDiacylglycerol lipase β inhibition reverses nociceptive behaviour in mouse models of inflammatory and neuropathic pain
Wilkerson J, Ghosh S, Bagdas D, Mason B, Crowe M, Hsu K, Wise L, Kinsey S, Damaj M, Cravatt B, Lichtman A. Diacylglycerol lipase β inhibition reverses nociceptive behaviour in mouse models of inflammatory and neuropathic pain. British Journal Of Pharmacology 2016, 173: 1678-1692. PMID: 26915789, PMCID: PMC4842918, DOI: 10.1111/bph.13469.Peer-Reviewed Original ResearchConceptsChronic constrictive injuryNeuropathic pain modelWild-type miceAllodynic responsesInflammatory painPain modelLPS modelSide effectsExpression of LPSDiscernible side effectsUntoward side effectsPro-inflammatory responseEvidence of toleranceSites of inflammationConstrictive injuryMechanical allodyniaIntraplantar injectionNeuropathic painPathological painInflammatory mediatorsMouse peritoneal macrophagesLocus of actionNociceptive behaviorSciatic nerveAllodynia