2020
Deficit in voluntary wheel running in chronic inflammatory and neuropathic pain models in mice: Impact of sex and genotype
Contreras KM, Caillaud M, Neddenriep B, Bagdas D, Roberts JL, Ulker E, White AB, Aboulhosn R, Toma W, Khalefa T, Adel A, Mann JA, Damaj MI. Deficit in voluntary wheel running in chronic inflammatory and neuropathic pain models in mice: Impact of sex and genotype. Behavioural Brain Research 2020, 399: 113009. PMID: 33181181, PMCID: PMC8961431, DOI: 10.1016/j.bbr.2020.113009.Peer-Reviewed Original ResearchConceptsNeuropathic pain modelChronic constriction injuryMechanical withdrawal thresholdPain modelStrains of miceWithdrawal thresholdDBA/2J miceVoluntary wheelChronic neuropathic pain modelPaclitaxel-treated miceVehicle-treated miceUnilateral intraplantar injectionLower mechanical thresholdsChronic pain reportQuality of lifeChemotherapy agent paclitaxelImpact of sexDifferent mouse strainsCCI miceCCI surgeryConstriction injuryIntraplantar injectionSham surgeryMale C57BL/6JNovel analgesicsPharmacologic Overview of Chlorogenic Acid and its Metabolites in Chronic Pain and Inflammation
Bagdas D, Gul Z, Meade JA, Cam B, Cinkilic N, Gurun MS. Pharmacologic Overview of Chlorogenic Acid and its Metabolites in Chronic Pain and Inflammation. Current Neuropharmacology 2020, 18: 216-228. PMID: 31631820, PMCID: PMC7327949, DOI: 10.2174/1570159x17666191021111809.Peer-Reviewed Original ResearchMeSH KeywordsAnalgesicsAnimalsAnti-Inflammatory AgentsChlorogenic AcidChronic PainDisease Models, AnimalEncephalitisHumansPlant ExtractsSepsisConceptsLiterature searchElectronic literature searchDifferent pathological situationsChlorogenic acidPharmacologic overviewNeuropathic painPain managementChronic painInflammatory insultPreventive roleAnimal modelsInflammationPotent antioxidantCertain foodsOxidative stressEthnopharmacological reportsPutative mechanismsDietary plantsAntioxidant defenseNatural phenolic compoundsPathological situationsPainMedicinal herbsOriginal articlesPhenolic compoundsAging protects rat cortical slices against to oxygen-glucose deprivation induced damage
Gul Z, Demircan C, Bagdas D, Buyukuysal RL. Aging protects rat cortical slices against to oxygen-glucose deprivation induced damage. International Journal Of Neuroscience 2020, 130: 1183-1191. PMID: 32064981, DOI: 10.1080/00207454.2020.1730830.Peer-Reviewed Original ResearchConceptsOxygen-glucose deprivationCortical slicesRat cortical slicesMale Sprague-DawleyAged male ratsOGD mediumS100B levelsLactate dehydrogenase leakageCerebral cortexControl conditionYoung slicesMale ratsSprague-DawleyAged animalsBrain regionsBrain tissueReoxygenationMore increaseStaining intensityDehydrogenase leakagePossible involvementMinutes incubationRatsPresent studySimilar decline
2019
Pharmacological mechanisms of alcohol analgesic-like properties in mouse models of acute and chronic pain
Neddenriep B, Bagdas D, Contreras K, Ditre J, Wolstenholme J, Miles M, Damaj M. Pharmacological mechanisms of alcohol analgesic-like properties in mouse models of acute and chronic pain. Neuropharmacology 2019, 160: 107793. PMID: 31562845, PMCID: PMC6924270, DOI: 10.1016/j.neuropharm.2019.107793.Peer-Reviewed Original ResearchConceptsAnalgesic-like propertiesComplete Freund's adjuvantAnti-nociceptive propertiesChronic painNeuropathic painChronic constriction injury modelAlcohol useMu-opioid systemOral ethanol administrationPain-like statePeripheral neuropathic painNeuropathic pain modelKappa-selective antagonistAcute alcohol useAnalgesic-like effectsDose-dependent reversalMechanical hypersensitivityAnalgesic effectNerve injuryPain modelAcute modelOpioid systemAcute alcoholFreund's adjuvantChronic useNeuropathic insult increases the responsiveness to acetic acid in mice.
Gurdap C, Markwalter P, Neddenriep B, Bagdas D, Damaj M. Neuropathic insult increases the responsiveness to acetic acid in mice. Behavioural Pharmacology 2019, 30: 534-537. PMID: 31033524, PMCID: PMC6684379, DOI: 10.1097/fbp.0000000000000486.Peer-Reviewed Original ResearchMeSH KeywordsAcetic AcidAnimalsConditioning, ClassicalDisease Models, AnimalHyperalgesiaMaleMiceMice, Inbred C57BLNeuralgiaNociceptionNociceptive PainSciatic NerveConceptsChronic constriction injuryChronic neuropathic painNeuropathic painPlace aversionAcute visceral painVehicle-treated micePeripheral nerve injuryPlace aversion (CPA) testPaclitaxel-treated animalsMillions of patientsCCI miceConstriction injuryVisceral painCCI animalsSham miceAcute painNerve injuryControl miceSciatic nerveNeuropathic insultMale miceNociceptive modelsPaclitaxel treatmentPainPlace conditioningC57BL/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
Monoacylglycerol lipase inhibitors reverse paclitaxel-induced nociceptive behavior and proinflammatory markers in a mouse model of chemotherapy-induced neuropathy
Curry Z, Wilkerson J, Bagdas D, Kyte S, Patel N, Donvito G, Mustafa M, Poklis J, Niphakis M, Hsu K, Cravatt B, Gewirtz D, Damaj M, Lichtman A. Monoacylglycerol lipase inhibitors reverse paclitaxel-induced nociceptive behavior and proinflammatory markers in a mouse model of chemotherapy-induced neuropathy. Journal Of Pharmacology And Experimental Therapeutics 2018, 366: jpet.117.245704. PMID: 29540562, PMCID: PMC6038031, DOI: 10.1124/jpet.117.245704.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsApoptosisBenzodioxolesBiomarkersCarbamatesCell Line, TumorCell ProliferationChemokine CCL2Disease Models, AnimalDose-Response Relationship, DrugEnzyme InhibitorsHumansHyperalgesiaInflammationMaleMiceMonoacylglycerol LipasesNociceptionP38 Mitogen-Activated Protein KinasesPaclitaxelPhosphoproteinsPiperidinesReceptor, Cannabinoid, CB1Receptor, Cannabinoid, CB2SuccinimidesConceptsAntinociceptive effectPaclitaxel-induced mechanical allodyniaPaclitaxel-induced neuropathic painH460 non-small cell lung cancer cellsNon-small cell lung cancer cellsMonoacylglycerol lipaseMonocyte chemoattractant protein-1Chemotherapy-induced neuropathyPaclitaxel-induced allodyniaPain side effectsPrimary hydrolytic enzymesCell lung cancer cellsSpinal dorsal hornDorsal root gangliaChemoattractant protein-1Novel pharmacologic strategiesPaclitaxel-treated animalsNumerous rodent modelsLung cancer cellsPlace preference paradigmMonoacylglycerol lipase inhibitorsIntrinsic rewarding effectsPhospho-p38 MAPKMechanical allodyniaNeuropathic painCurcumin 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
2017
Nicotine prevents and reverses paclitaxel-induced mechanical allodynia in a mouse model of CIPN
Kyte S, Toma W, Bagdas D, Meade J, Schurman L, Lichtman A, Chen Z, Del Fabbro E, Fang X, Bigbee J, Damaj M, Gewirtz D. Nicotine prevents and reverses paclitaxel-induced mechanical allodynia in a mouse model of CIPN. Journal Of Pharmacology And Experimental Therapeutics 2017, 364: jpet.117.243972. PMID: 29042416, PMCID: PMC5738719, DOI: 10.1124/jpet.117.243972.Peer-Reviewed Original ResearchConceptsChemotherapy-induced peripheral neuropathyPaclitaxel-induced mechanical allodyniaMechanical allodyniaPeripheral neuropathyMouse modelTreatment of CIPNLewis lung carcinoma tumor growthIntraepidermal nerve fiber lossPaclitaxel-induced peripheral neuropathyH460 non-small cell lung cancer cellsNon-small cell lung cancer cellsLung tumor cell proliferationNerve fiber dysfunctionNicotinic acetylcholine receptor subtypesCell lung cancer cellsChronic nicotine administrationNerve fiber lossChronic nicotine treatmentMale C57BL/6J miceAcetylcholine receptor subtypesLung cancer cellsProliferation of A549Receptor-mediated pathwayTumor cell proliferationCIPN treatmentAllosteric modulation of α4β2* nicotinic acetylcholine receptors: Desformylflustrabromine potentiates antiallodynic response of nicotine in a mouse model of neuropathic pain
Bagdas D, Ergun D, Jackson A, Toma W, Schulte M, Damaj M. Allosteric modulation of α4β2* nicotinic acetylcholine receptors: Desformylflustrabromine potentiates antiallodynic response of nicotine in a mouse model of neuropathic pain. European Journal Of Pain 2017, 22: 84-93. PMID: 28809075, PMCID: PMC9829446, DOI: 10.1002/ejp.1092.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric RegulationAnimalsDisease Models, AnimalHydrocarbons, BrominatedIndole AlkaloidsMaleMiceNeuralgiaNicotineNicotinic AgonistsReceptors, NicotinicConceptsPositive allosteric modulatorsChronic neuropathic painNeuropathic painΑ4β2 nAChRsNicotinic acetylcholine receptorsAllosteric modulationAcetylcholine receptorsAntagonist dihydro-β-erythroidineNeuronal nicotinic acetylcholine receptorsChronic constriction injuryEndogenous cholinergic toneNicotine-evoked responsesAnimal pain modelsNicotine-induced antinociceptionDihydro-β-erythroidineMediation of painAlternative treatment strategiesBehavior doseConstriction injuryAntiallodynic effectPain modelPain modulationCholinergic tonePain behaviorAntinociceptive propertiesEffects of Adrenomedullin and Glucagon-like Peptide on Distal Flap Necrosis and Vascularity: The Role of Receptor Systems and Nitric Oxide.
Cam B, Bagdas D, Ozyigit M, Sagdilek E, Buyukcoskun N, Ozluk K. Effects of Adrenomedullin and Glucagon-like Peptide on Distal Flap Necrosis and Vascularity: The Role of Receptor Systems and Nitric Oxide. WOUNDS A Compendium Of Clinical Research And Practice 2017, 29: 163-167. PMID: 28355142.Peer-Reviewed Original ResearchMeSH KeywordsAdrenomedullinAnimalsAntioxidantsCalcitonin Gene-Related PeptideDisease Models, AnimalEpigastric ArteriesFemaleGlucagon-Like Peptide ReceptorsGlucagon-Like PeptidesGraft SurvivalImmunohistochemistryNecrosisNitric OxideRatsRats, WistarReceptors, Calcitonin Gene-Related PeptideSurgical FlapsWound HealingWounds and InjuriesConceptsGlucagon-like peptide-1Superficial inferior epigastric arteryEffects of adrenomedullinFlap healingNitric oxideFlap necrosisReceptor antagonistNecrosis areaGLP-1 receptor antagonistCalcitonin gene-related peptide receptorAdult female Wistar ratsGene-related peptide receptorBeneficial effectsADM receptor antagonistAdministration of adrenomedullinPostoperative day 7Inferior epigastric arteryGLP-1 receptorDistal flap necrosisFemale Wistar ratsGlucagon-like peptideMajor complicationsCGRP receptorsEpigastric arteryWistar ratsIn vivo interactions between α7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α: Implication for nicotine dependence
Jackson A, Bagdas D, Muldoon PP, Lichtman AH, Carroll FI, Greenwald M, Miles MF, Damaj MI. In vivo interactions between α7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α: Implication for nicotine dependence. Neuropharmacology 2017, 118: 38-45. PMID: 28279662, PMCID: PMC5410388, DOI: 10.1016/j.neuropharm.2017.03.005.Peer-Reviewed Original ResearchMeSH KeywordsAlpha7 Nicotinic Acetylcholine ReceptorAnesthetics, LocalAnimalsBenzamidesBridged Bicyclo CompoundsCocaineConditioning, OperantDisease Models, AnimalFenofibrateHypolipidemic AgentsMaleMiceMice, Inbred ICRNicotineNicotinic AgonistsOxazolesPPAR alphaPyrimidinesSelf AdministrationSubstance Withdrawal SyndromeTobacco Use DisorderTyrosineConceptsNicotine dependenceNicotinic acetylcholine receptorsNicotine rewardΑ7 nAChRsNicotine CPPWY-14643Acetylcholine receptorsRewarding propertiesNuclear peroxisome proliferator-activated receptorsΑ7 nicotinic acetylcholine receptorVentral tegmental area dopamine cellsEffect of α7Peroxisome proliferator-activated receptorNicotine withdrawal signsSmoking cessation therapyChronic tobacco useCurrent smoking cessation therapiesPPARα antagonist GW6471Main addictive componentPPARα-dependent mannerProliferator-activated receptorNicotine rewarding propertiesPlace preference testHomomeric α7 nAChRsSelf-administration model
2016
Sex Differences and Drug Dose Influence the Role of the α7 Nicotinic Acetylcholine Receptor in the Mouse Dextran Sodium Sulfate-Induced Colitis Model
AlSharari S, Bagdas D, Akbarali H, Lichtman P, Raborn E, Cabral G, Carroll F, McGee E, Damaj M. Sex Differences and Drug Dose Influence the Role of the α7 Nicotinic Acetylcholine Receptor in the Mouse Dextran Sodium Sulfate-Induced Colitis Model. Nicotine & Tobacco Research 2016, 19: 460-468. PMID: 27639096, PMCID: PMC6894014, DOI: 10.1093/ntr/ntw245.Peer-Reviewed Original ResearchConceptsΑ7 nicotinic acetylcholine receptorWild-type miceColitis severityNicotinic acetylcholine receptorsFemale miceHigher tumor necrosis factor-alpha levelsAcetylcholine receptorsTumor necrosis factor-alpha levelsNecrosis factor-alpha levelsLittermate wild-type miceAnti-colitis activityAnti-colitis effectΑ7 knockout miceDextran sodium sulfatePathogenesis of colitisAnti-inflammatory effectsFemale adult miceViable therapeutic approachSeverity of diseaseSex differencesColon lengthDisease activityColonic levelsColitis modelUlcerative colitisThe 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
2014
Effects of methoxsalen, a CYP2A5/6 inhibitor, on nicotine dependence behaviors in mice
Bagdas D, Muldoon P, Zhu A, Tyndale R, Damaj M. Effects of methoxsalen, a CYP2A5/6 inhibitor, on nicotine dependence behaviors in mice. Neuropharmacology 2014, 85: 67-72. PMID: 24859605, PMCID: PMC4106981, DOI: 10.1016/j.neuropharm.2014.05.006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnxietyAryl Hydrocarbon HydroxylasesConditioning, PsychologicalCytochrome P450 Family 2Disease Models, AnimalDose-Response Relationship, DrugEnzyme InhibitorsHyperalgesiaMaleMecamylamineMethoxsalenMice, Inbred ICRMotor ActivityNicotineNicotinic AgonistsNicotinic AntagonistsRewardSeverity of Illness IndexSubstance Withdrawal SyndromeTobacco Use DisorderConceptsNicotine plasma levelsWithdrawal signsPlasma levelsAdministration of methoxsalenEffect of methoxsalenNicotine dependence behaviorsNicotine replacement therapyChronic nicotine infusionDependence-related behaviorsDrug elimination ratePlace preference testMetabolism of nicotineReward-like propertiesLack of enhancementSpontaneous withdrawalNicotine withdrawalReplacement therapyNicotine preferenceLow doseHigh doseNicotine infusionMouse CYP2A5CPP testActive nicotineNicotine levels
2013
Preclinical evidence for the antihyperalgesic activity of CDP-choline in oxaliplatin-induced neuropathic pain.
Kanat O, Bagdas D, Ozboluk H, Gurun M. Preclinical evidence for the antihyperalgesic activity of CDP-choline in oxaliplatin-induced neuropathic pain. JBUON 2013, 18: 1012-8. PMID: 24344031.Peer-Reviewed Original ResearchMeSH KeywordsAnalgesicsAnimalsCytidine Diphosphate CholineDisease Models, AnimalDose-Response Relationship, DrugGABA-B Receptor AntagonistsHyperalgesiaInjections, IntraventricularMaleNeuralgiaNeurotransmitter Uptake InhibitorsNicotinic AntagonistsOrganoplatinum CompoundsOxaliplatinPain ThresholdRatsRats, Sprague-DawleyTime FactorsConceptsAntihyperalgesic effectNeuropathic painCDP-cholineNonselective muscarinic receptor antagonist atropineNonselective opioid receptor antagonist naloxoneRat paw pressure testReceptor antagonist CGP 35348Muscarinic receptor antagonist atropineNicotinic receptor antagonist mecamylamineOpioid receptor antagonist naloxoneOxaliplatin-induced neuropathic painCholine uptake inhibitor hemicholinium-3Induction of neuropathyAntagonist CGP 35348Paw pressure testGamma-amino butyric acidNicotinic acetylcholine receptorsCGP 35348Neuropatic painMechanical hyperalgesiaAntagonist atropineTime-dependent mannerPreclinical evidenceAntagonist naloxoneAntihyperalgesic activity
2011
The antihyperalgesic effect of cytidine-5′-diphosphate-choline in neuropathic and inflammatory pain models
Bagdas D, Sonat F, Hamurtekin E, Sonal S, Gurun M. The antihyperalgesic effect of cytidine-5′-diphosphate-choline in neuropathic and inflammatory pain models. Behavioural Pharmacology 2011, 22: 589-598. PMID: 21836465, DOI: 10.1097/fbp.0b013e32834a1efb.Peer-Reviewed Original ResearchConceptsNeuropathic pain modelAntihyperalgesic effectPain modelChronic constriction injury-induced neuropathic pain modelNonselective muscarinic receptor antagonist atropineNonselective opioid receptor antagonist naloxoneΓ-aminobutyric acid B receptorsNicotinic ACh receptor antagonistsReceptor antagonist CGP 35348Muscarinic receptor antagonist atropineNicotinic receptor antagonist mecamylamineOpioid receptor antagonist naloxoneCholine uptake inhibitor hemicholinium-3CDP-cholineEffect of intracerebroventricularlyAntagonist CGP 35348Central opioid receptorsInflammatory pain modelACh receptor antagonistNicotinic ACh receptorsCGP 35348Mechanical hyperalgesiaNeuropathic painAntagonist atropineAntagonist naloxone
2007
Possible involvement of supraspinal opioid and GABA receptors in CDP-choline-induced antinociception in acute pain models in rats
Hamurtekin E, Bagdas D, Gurun M. Possible involvement of supraspinal opioid and GABA receptors in CDP-choline-induced antinociception in acute pain models in rats. Neuroscience Letters 2007, 420: 116-121. PMID: 17531379, DOI: 10.1016/j.neulet.2007.04.058.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAdrenergic alpha-AntagonistsAnalgesicsAnimalsBrainCytidine Diphosphate CholineDisease Models, AnimalEfferent PathwaysGABA AntagonistsInjections, IntraventricularMaleNarcotic AntagonistsNociceptorsPainPain MeasurementPain ThresholdRatsRats, Sprague-DawleyReceptors, Adrenergic, alphaReceptors, GABAReceptors, GABA-BReceptors, OpioidReceptors, SerotoninSerotonin AntagonistsConceptsAcute pain modelsMechanical paw pressure testThermal paw withdrawal testPaw pressure testPaw withdrawal testAntinociceptive effectPain modelSupraspinal opioidsSerotonergic receptorsAlpha-1 adrenergic receptor antagonist prazosinCDP-cholineWithdrawal testOpioid receptor antagonist naloxoneAdrenergic receptor antagonist prazosinAdrenergic receptor antagonist yohimbineCytidine-5′-diphosphate cholineDifferent pain modelsExerts antinociceptive effectsDose-dependent antinociceptionReceptor antagonist yohimbineReceptor antagonist prazosinReceptor-mediated mechanismMethysergide pretreatmentAntagonist yohimbineAntagonist prazosin