2024
Nav1.8 in small dorsal root ganglion neurons contributes to vincristine-induced mechanical allodynia
Nascimento de Lima A, Zhang H, Chen L, Effraim P, Gomis-Perez C, Cheng X, Huang J, Waxman S, Dib-Hajj S. Nav1.8 in small dorsal root ganglion neurons contributes to vincristine-induced mechanical allodynia. Brain 2024, 147: 3157-3170. PMID: 38447953, DOI: 10.1093/brain/awae071.Peer-Reviewed Original ResearchDorsal root ganglion neuronsDorsal root ganglionVincristine-induced mechanical allodyniaVincristine-induced peripheral neuropathyMechanical allodyniaVincristine treatmentNav1.8 channelsSmall dorsal root ganglion neuronsDevelopment of mechanical allodyniaTTX-R current densityVoltage-gated sodium channel Nav1.6Vincristine-treated animalsCurrent-clamp recordingsSodium channel Nav1.8Voltage-clamp recordingsReducing current thresholdSodium channel Nav1.6Investigate pathophysiological mechanismsTTX-RHyperpolarizing shiftRoot ganglionAllodyniaGanglion neuronsVincristine administrationPeripheral neuropathyVagus nerve stimulation rescues persistent pain following orthopedic surgery in adult mice
Wu P, Caceres A, Chen J, Sokoloff J, Huang M, Baht G, Nackley A, Jordt S, Terrando N. Vagus nerve stimulation rescues persistent pain following orthopedic surgery in adult mice. Pain 2024, 165: e80-e92. PMID: 38422485, PMCID: PMC11247455, DOI: 10.1097/j.pain.0000000000003181.Peer-Reviewed Original ResearchDorsal root gangliaPostoperative painVagus nerve stimulationPain behaviorOrthopedic surgeryNerve stimulationHindpaw mechanical allodyniaPrevent postoperative painFemale C57BL/6J miceOrthopedic trauma surgeryMechanical allodyniaAntinociceptive effectPersistent painAccelerated bone healingAnalgesic effectAdult miceC57BL/6J miceEffective therapyNeuropeptide levelsSpinal cordMouse modelSatellite cellsSurgeryPainVagus nerve
2023
Targeting a xenobiotic transporter to ameliorate vincristine-induced sensory neuropathy
Li Y, Drabison T, Nepal M, Ho R, Leblanc A, Gibson A, Jin Y, Yang W, Huang K, Uddin M, Chen M, DiGiacomo D, Chen X, Razzaq S, Tonniges J, McTigue D, Mims A, Lustberg M, Wang Y, Hummon A, Evans W, Baker S, Cavaletti G, Sparreboom A, Hu S. Targeting a xenobiotic transporter to ameliorate vincristine-induced sensory neuropathy. JCI Insight 2023, 8: e164646. PMID: 37347545, PMCID: PMC10443802, DOI: 10.1172/jci.insight.164646.Peer-Reviewed Original ResearchConceptsPeripheral neurotoxicitySide effectsDose-limiting peripheral neurotoxicityDorsal root ganglion neuronsMultiple malignant diseasesUptake of vincristineAction potential amplitudeEffective preventative treatmentMechanical allodyniaThermal hyperalgesiaSensory neuropathyGanglion neuronsMalignant diseasePlasma levelsDose selectionVincristine accumulationUntargeted metabolomics analysisAntitumor effectsClinical developmentPotential amplitudePreventative treatmentNeuronal transporterNeuronal morphologyVincristinePharmacological inhibition
2021
Anti-AQP4 autoantibodies promote ATP release from astrocytes and induce mechanical pain in rats
Ishikura T, Kinoshita M, Shimizu M, Yasumizu Y, Motooka D, Okuzaki D, Yamashita K, Murata H, Beppu S, Koda T, Tada S, Shiraishi N, Sugiyama Y, Miyamoto K, Kusunoki S, Sugimoto T, Kumanogoh A, Okuno T, Mochizuki H. Anti-AQP4 autoantibodies promote ATP release from astrocytes and induce mechanical pain in rats. Journal Of Neuroinflammation 2021, 18: 181. PMID: 34419102, PMCID: PMC8380350, DOI: 10.1186/s12974-021-02232-w.Peer-Reviewed Original ResearchConceptsNeuromyelitis optica spectrum disorderIgG-treated ratsMechanical allodyniaNeuropathic painSpinal cordATP receptorsATP releaseSymptoms of neuromyelitis optica spectrum disorderDevelopment of mechanical allodyniaDevelopment of neuropathic painPharmacological inhibitionDevelopment of painful symptomsAnti-AQP4 autoantibodiesPeripheral neuropathic painAnti-AQP4 antibodyRelease of extracellular ATPExtracellular ATP releaseRat spinal cordDamage-associated molecular patternsAnti-AQP4Pain mechanismsMechanical painInvolvement of ATPPain symptomsRemission phase(E)-3-furan-2-yl-N-phenylacrylamide (PAM-4) decreases nociception and emotional manifestations of neuropathic pain in mice by α7 nicotinic acetylcholine receptor potentiation
Bagdas D, Sevdar G, Gul Z, Younis R, Cavun S, Tae HS, Ortells MO, Arias HR, Gurun MS. (E)-3-furan-2-yl-N-phenylacrylamide (PAM-4) decreases nociception and emotional manifestations of neuropathic pain in mice by α7 nicotinic acetylcholine receptor potentiation. Neurological Research 2021, 43: 1056-1068. PMID: 34281483, DOI: 10.1080/01616412.2021.1949684.Peer-Reviewed Original ResearchConceptsPositive allosteric modulationΑ7 nAChRsNeuropathic painΑ7-selective antagonist methyllycaconitineΑ7 nicotinic acetylcholine receptorChronic constriction injuryPaw licking behaviorNeuropathic pain modelAcute systemic administrationChronic painful conditionsAntidepressant-like activityAnti-nociceptive activityDepression-like behaviorAnxiogenic-like effectsNicotinic acetylcholine receptorsAffective behaviorHuman α7 nAChRConstriction injuryMechanical allodyniaFormalin testPain modelAntagonist methyllycaconitineChronic painPainful conditionsRat α7 nAChR
2020
Exome Sequencing Implicates Impaired GABA Signaling and Neuronal Ion Transport in Trigeminal Neuralgia
Dong W, Jin SC, Allocco A, Zeng X, Sheth AH, Panchagnula S, Castonguay A, Lorenzo LÉ, Islam B, Brindle G, Bachand K, Hu J, Sularz A, Gaillard J, Choi J, Dunbar A, Nelson-Williams C, Kiziltug E, Furey CG, Conine S, Duy PQ, Kundishora AJ, Loring E, Li B, Lu Q, Zhou G, Liu W, Li X, Sierant MC, Mane S, Castaldi C, López-Giráldez F, Knight JR, Sekula RF, Simard JM, Eskandar EN, Gottschalk C, Moliterno J, Günel M, Gerrard JL, Dib-Hajj S, Waxman SG, Barker FG, Alper SL, Chahine M, Haider S, De Koninck Y, Lifton RP, Kahle KT. Exome Sequencing Implicates Impaired GABA Signaling and Neuronal Ion Transport in Trigeminal Neuralgia. IScience 2020, 23: 101552. PMID: 33083721, PMCID: PMC7554653, DOI: 10.1016/j.isci.2020.101552.Peer-Reviewed Original ResearchTrigeminal neuralgiaNeuronal ion transportImpairment of GABAVoltage-gated CaMechanical allodyniaTN pathogenesisPain syndromePain behaviorGABA signalingReceptor ClDisease pathogenesisTN casesFamilial clusteringExome sequencingGenetic factorsVariant burdenNeuralgiaRare damaging variantsPathogenesisGABAChannel CaDamaging variantsProbandsParent-offspring triosLarge-scale genomic studies
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: 169-183. 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 pain
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: 110-119. 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 treatmentTransient Receptor Potential Cation Channel Subfamily M Member 8 channels mediate the anti‐inflammatory effects of eucalyptol
Caceres AI, Liu B, Jabba SV, Achanta S, Morris JB, Jordt S. Transient Receptor Potential Cation Channel Subfamily M Member 8 channels mediate the anti‐inflammatory effects of eucalyptol. British Journal Of Pharmacology 2017, 174: 867-879. PMID: 28240768, PMCID: PMC5387001, DOI: 10.1111/bph.13760.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Infective AgentsAnti-Inflammatory AgentsCyclohexanolsDose-Response Relationship, DrugEdemaEucalyptolFemaleHEK293 CellsHumansInflammationInflammation MediatorsMaleMiceMice, Inbred C57BLMice, KnockoutMonoterpenesRandom AllocationTransient Receptor Potential ChannelsTRPM Cation ChannelsConceptsAnti-inflammatory effectsComplete Freund's adjuvantTRPM8 channelsPulmonary inflammationLeukocyte infiltrationNovel anti-inflammatory agentsInflammatory pain responsesSelective TRPM8 agonistsAdministration of LPSAnti-inflammatory propertiesChannel-deficient miceAnti-inflammatory agentsEffect of eucalyptolProduction of TNFTRP cation channelsMechanical allodyniaChemokine levelsTRPM8 agonistMyeloperoxidase activityFootpad inflammationFreund's adjuvantPain responseIL-1βIL-6Inflammatory cytokines
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 nerveAllodyniaStriatal-enriched protein tyrosine phosphatase modulates nociception
Azkona G, Saavedra A, Aira Z, Aluja D, Xifró X, Baguley T, Alberch J, Ellman JA, Lombroso PJ, Azkue JJ, Pérez-Navarro E. Striatal-enriched protein tyrosine phosphatase modulates nociception. Pain 2016, 157: 377-386. PMID: 26270590, PMCID: PMC4809206, DOI: 10.1097/j.pain.0000000000000329.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzothiepinsDisease Models, AnimalEnzyme InhibitorsEvoked PotentialsFemaleGene Expression RegulationHyperalgesiaInflammationMaleMAP Kinase Signaling SystemMiceMice, Inbred C57BLMice, TransgenicNerve Fibers, UnmyelinatedNociceptionPainPain ThresholdProtein Tyrosine Phosphatases, Non-ReceptorRatsRats, Sprague-DawleySignal TransductionConceptsLumbar spinal cordSpinal cordThermal hyperalgesiaStriatal-enriched protein tyrosine phosphataseInflammatory painAdjuvant injectionC fibre-evoked spinal field potentialsKnockout miceComplete Freund's adjuvant injectionModulation of nociceptionFreund's adjuvant injectionProtein levelsSpinal field potentialsSTEP knockout miceGender-related differencesMechanical allodyniaCentral sensitizationInactivation of ERK1/2Dorsal hornFemale miceFemale genderInhibitory interneuronsPharmacological approachesHyperalgesiaBehavioral tests
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 edemaChronic Compression of the Dorsal Root Ganglion Enhances Mechanically Evoked Pain Behavior and the Activity of Cutaneous Nociceptors in Mice
Wang T, Hurwitz O, Shimada SG, Qu L, Fu K, Zhang P, Ma C, LaMotte RH. Chronic Compression of the Dorsal Root Ganglion Enhances Mechanically Evoked Pain Behavior and the Activity of Cutaneous Nociceptors in Mice. PLOS ONE 2015, 10: e0137512. PMID: 26356638, PMCID: PMC4565551, DOI: 10.1371/journal.pone.0137512.Peer-Reviewed Original ResearchConceptsDorsal root gangliaPunctate mechanical stimuliSpontaneous activityChronic compressionCutaneous nociceptorsL3 dorsal root gangliaPost-operative day 2Evoked pain behaviorsPain-like behaviorsVon Frey filamentsDorsum of footUnoperated control miceMechanical stimuliCutaneous C nociceptorsBehavioral hyperalgesiaCCD surgeryIntraforaminal stenosisMechanical allodyniaRadicular painC-nociceptorsDRG neuronsPain behaviorControl miceEnhanced excitabilityControl neuronsThe 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 behaviorPain
2013
Burn injury-induced mechanical allodynia is maintained by Rac1-regulated dendritic spine dysgenesis
Tan AM, Samad OA, Liu S, Bandaru S, Zhao P, Waxman SG. Burn injury-induced mechanical allodynia is maintained by Rac1-regulated dendritic spine dysgenesis. Experimental Neurology 2013, 248: 509-519. PMID: 23933578, DOI: 10.1016/j.expneurol.2013.07.017.Peer-Reviewed Original ResearchConceptsDendritic spine dysgenesisWDR neuronsNeuropathic painBurn injurySpine dysgenesisMechanical allodyniaInjury-induced chronic painInjury-induced mechanical allodyniaSpinal cord dorsal hornBurn-injured animalsHindpaw receptive fieldsInjury-induced painNeuropathic pain phenotypesSecond-degree burn injurySecond-degree burn modelDendritic spine morphologyDendritic spine shapeDorsal hornIntractable painMechanical painPain managementChronic painPain phenotypesElectrophysiological signsPreclinical models
2009
Unilateral Focal Burn Injury Is Followed by Long-Lasting Bilateral Allodynia and Neuronal Hyperexcitability in Spinal Cord Dorsal Horn
Chang YW, Tan A, Saab C, Waxman S. Unilateral Focal Burn Injury Is Followed by Long-Lasting Bilateral Allodynia and Neuronal Hyperexcitability in Spinal Cord Dorsal Horn. Journal Of Pain 2009, 11: 119-130. PMID: 19744891, DOI: 10.1016/j.jpain.2009.06.009.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnalysis of VarianceAnimalsBrain InjuriesCalcitonin Gene-Related PeptideCD11b AntigenDisease Models, AnimalFunctional LateralityHyperesthesiaMaleMicrogliap38 Mitogen-Activated Protein KinasesPainPain MeasurementPain ThresholdPhysical StimulationPosterior Horn CellsRatsSpinal CordSubstance PConceptsSpinal cord dorsal hornBurn injuryBurn injury modelBilateral allodyniaDorsal hornNeuronal hyperexcitabilityInjury modelSpinal cordDorsal horn neuronal hyperexcitabilitySecond-order sensory neuronsCentral neuropathic mechanismsIpsilateral mechanical allodyniaDorsal horn neuronsActivation of microgliaPathogenesis of painPotential therapeutic targetNovel animal modelContralateral allodyniaMechanical allodyniaNeuropathic mechanismsSpinal microgliaBilateral painMicroglial activationNerve injuryWeeks postinjury
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