2019
A silent agonist of α7 nicotinic acetylcholine receptors modulates inflammation ex vivo and attenuates EAE
Godin J, Roy P, Quadri M, Bagdas D, Toma W, Narendrula-Kotha R, Kishta O, Damaj M, Horenstein N, Papke R, Simard A. A silent agonist of α7 nicotinic acetylcholine receptors modulates inflammation ex vivo and attenuates EAE. Brain Behavior And Immunity 2019, 87: 286-300. PMID: 31874200, PMCID: PMC7604877, DOI: 10.1016/j.bbi.2019.12.014.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptorsSilent agonistInflammatory painCytokine productionΑ7 nAChRsAnimal modelsAcetylcholine receptorsΑ7 nicotinic acetylcholine receptorNon-neuronal nAChRsExperimental autoimmune encephalomyelitisChronic inflammatory painAnti-inflammatory compoundsInflammation ex vivoChannel openingAutoimmune encephalomyelitisAntagonist mecamylamineMultiple sclerosisInflammatory disordersModulates inflammationMacrophage numbersDisease manifestationsNervous systemReceptor desensitizationInflammationAgonistsC57BL/6 substrain differences in inflammatory and neuropathic nociception and genetic mapping of a major quantitative trait locus underlying acute thermal nociception
Bryant C, Bagdas D, Goldberg L, Khalefa T, Reed E, Kirkpatrick S, Kelliher J, Chen M, Johnson W, Mulligan M, Damaj M. C57BL/6 substrain differences in inflammatory and neuropathic nociception and genetic mapping of a major quantitative trait locus underlying acute thermal nociception. Molecular Pain 2019, 15: 1744806918825046. PMID: 30632432, PMCID: PMC6365993, DOI: 10.1177/1744806918825046.Peer-Reviewed Original ResearchConceptsAcute thermal nociceptionThermal nociceptionNerve injuryNociceptive behaviorPain modalitiesB6N miceAdjuvant modelComplete Freund's adjuvant (CFA) modelChronic constrictive nerve injuryBaseline mechanical thresholdInflammatory nociceptive behaviorsInflammatory nociceptive stimulusStrain differencesFreund's adjuvant modelDifferent pain modalitiesHot plate testPreclinical pain modelsHot plate sensitivityNeuropathic nociceptionNociceptive markersPaw diameterMechanical hypersensitivityInflammatory painNeuropathic painPain model
2018
The antinociceptive and anti-inflammatory properties of the α7 nAChR weak partial agonist p-CF3 N,N-diethyl-N’-phenylpiperazine
Quadri M, Bagdas D, Toma W, Stokes C, Horenstein N, Damaj M, Papke R. The antinociceptive and anti-inflammatory properties of the α7 nAChR weak partial agonist p-CF3 N,N-diethyl-N’-phenylpiperazine. Journal Of Pharmacology And Experimental Therapeutics 2018, 367: jpet.118.249904. PMID: 30111636, PMCID: PMC7593094, DOI: 10.1124/jpet.118.249904.Peer-Reviewed Original ResearchConceptsAntinociceptive activitySelective antagonist methyllycaconitineAnti-inflammatory therapyAnti-inflammatory componentsAnti-inflammatory propertiesPositive allosteric modulatorsNon-neuronal cellsNicotinic acetylcholine receptorsVivo antinociceptive activityAntiedema effectInflammatory painAntagonist methyllycaconitineChronic painInflammatory diseasesHeteromeric nAChRsReceptor subtypesElectrophysiological profileNoncompetitive antagonistAcetylcholine receptorsAgonist activityPartial agonistAllosteric modulatorsSuch drugsPromising drug targetSilent agonistCurcumin acts as a positive allosteric modulator of α7-nicotinic acetylcholine receptors and reverses nociception in mouse models of inflammatory pain
El Nebrisi E, Bagdas D, Toma W, Al Samri H, Brodzik A, Alkhlaif Y, Yang K, Howarth F, Damaj I, Oz M. Curcumin acts as a positive allosteric modulator of α7-nicotinic acetylcholine receptors and reverses nociception in mouse models of inflammatory pain. Journal Of Pharmacology And Experimental Therapeutics 2018, 365: jpet.117.245068. PMID: 29339457, PMCID: PMC7947331, DOI: 10.1124/jpet.117.245068.Peer-Reviewed Original ResearchConceptsEffect of curcuminPositive allosteric modulatorsMouse modelVisceral painAntinociceptive effectNACh receptorsAcetylcholine receptorsAllosteric modulatorsΑ7 nicotinic acetylcholine receptorVisceral pain modelHuman nicotinic acetylcholine receptorNicotinic acetylcholine receptorsInflammatory painPain modelNociceptive behaviorReceptor agonistSignificant potentiationDependent ClLocomotor activityACh concentrationPainNociceptionReceptorsTonicG proteins
2016
Diacylglycerol 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
2015
The Antinociceptive and Antiinflammatory Properties of 3-furan-2-yl-N-p-tolyl-acrylamide, a Positive Allosteric Modulator of &agr;7 Nicotinic Acetylcholine Receptors in Mice
Bagdas D, Targowska-Duda K, López J, Perez E, Arias H, Damaj M. The Antinociceptive and Antiinflammatory Properties of 3-furan-2-yl-N-p-tolyl-acrylamide, a Positive Allosteric Modulator of &agr;7 Nicotinic Acetylcholine Receptors in Mice. Anesthesia & Analgesia 2015, 121: 1369-1377. PMID: 26280585, PMCID: PMC4847442, DOI: 10.1213/ane.0000000000000902.Peer-Reviewed Original ResearchConceptsPositive allosteric modulatorsType II positive allosteric modulatorsNeuropathic pain modelInflammatory painNicotinic acetylcholine receptorsNeuropathic painPain modelCarrageenan testAntiinflammatory propertiesChronic constriction injury-induced neuropathic painAcetylcholine receptorsInjury-induced neuropathic painAllosteric modulatorsΑ7 nicotinic acetylcholine receptorSelective α7 agonistPlace aversion (CPA) testExperience of painEfficacy of agonistsEndogenous neurotransmissionMechanical allodyniaThermal hyperalgesiaTime-dependent mannerAntinociceptive effectComplete Freund'sPaw edemaThe role of alpha5 nicotinic acetylcholine receptors in mouse models of chronic inflammatory and neuropathic pain
Bagdas D, AlSharari S, Freitas K, Tracy M, Damaj M. The role of alpha5 nicotinic acetylcholine receptors in mouse models of chronic inflammatory and neuropathic pain. Biochemical Pharmacology 2015, 97: 590-600. PMID: 25931144, PMCID: PMC4600420, DOI: 10.1016/j.bcp.2015.04.013.Peer-Reviewed Original ResearchConceptsΑ5-KO miceΑ5 nAChRInflammatory painFormalin testPain modelChronic painMouse modelTumor necrosis factor-alpha levelsLong-term inflammatory painNecrosis factor-alpha levelsPaw-licking timeTonic inflammatory painChronic pain modelsDevelopment of hyperalgesiaInflammatory pain modelWild-type miceNicotinic acetylcholine receptorsAllodynic responsesMechanical allodyniaNicotine reversalCFA injectionNeuropathic painAntinociceptive effectNociceptive behaviorPainEffects of GAT107, an Allosteric Agonist and Positive Modulator of α7 Nicotinic Acetylcholine Receptors, on Chronic Inflammatory and Neuropathic Pain in Mice
Bagdas D, Wilkerson J, Lichtman A, Thakur G, Damaj M. Effects of GAT107, an Allosteric Agonist and Positive Modulator of α7 Nicotinic Acetylcholine Receptors, on Chronic Inflammatory and Neuropathic Pain in Mice. The FASEB Journal 2015, 29 DOI: 10.1096/fasebj.29.1_supplement.616.12.Peer-Reviewed Original ResearchPositive allosteric modulatorsΑ7 nicotinic acetylcholine receptorNeuropathic painNicotinic acetylcholine receptorsAntinociceptive effectAgo-PAMChronic constriction injury-induced neuropathic painAcetylcholine receptorsAllosteric agonistInjury-induced neuropathic painPain-induced aversionAcetic acid injectionNew pharmacological approachesPlace aversion (CPA) testNovel therapeutic approachesAcute thermal stimulusMassey Cancer CenterComplete Freud'sInflammatory painChronic inflammatoryFormalin testPain modulationPain behaviorCancer CenterSystemic administration