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
Supraspinal Sensorimotor and Pain-Related Reorganization after a Hemicontusion Rat Cervical Spinal Cord Injury
Sanganahalli BG, Chitturi J, Herman P, Elkabes S, Heary R, Hyder F, Kannurpatti SS. Supraspinal Sensorimotor and Pain-Related Reorganization after a Hemicontusion Rat Cervical Spinal Cord Injury. Journal Of Neurotrauma 2021, 38: 3393-3405. PMID: 34714150, PMCID: PMC8713267, DOI: 10.1089/neu.2021.0190.Peer-Reviewed Original ResearchConceptsSpinal cord injuryCervical spinal cord injuryAnterior cingulate cortexFunctional magnetic resonance imagingPre-frontal cortexNociceptive regionsCord injuryPresence of painSecondary somatosensory cortexFunctional connectivity densityElectrical forepaw stimulationFemale adult ratsTranslational animal modelsMost cortical regionsMagnetic resonance imagingDiscernable lesionsIpsilesional forelimbKdyn forceRSFC decreasesRsFC increasesSupraspinal changesMotor recoveryThermal hyperalgesiaT2 lesionsPain behavior
2020
Two independent mouse lines carrying the Nav1.7 I228M gain-of-function variant display dorsal root ganglion neuron hyperexcitability but a minimal pain phenotype
Chen L, Wimalasena NK, Shim J, Han C, Lee SI, Gonzalez-Cano R, Estacion M, Faber CG, Lauria G, Dib-Hajj S, Woolf CJ, Waxman SG. Two independent mouse lines carrying the Nav1.7 I228M gain-of-function variant display dorsal root ganglion neuron hyperexcitability but a minimal pain phenotype. Pain 2020, 162: 1758-1770. PMID: 33323889, PMCID: PMC8119301, DOI: 10.1097/j.pain.0000000000002171.Peer-Reviewed Original ResearchConceptsSmall fiber neuropathyDorsal root ganglion neuron hyperexcitabilityNeuron hyperexcitabilityMouse linesIdiopathic small fiber neuropathyIntraepidermal nerve fiber lossPainful small fiber neuropathyFunction variantsDRG neuron hyperexcitabilityNerve fiber lossSodium channel Nav1.7Multielectrode array recordingsNeuropathic painThermal hyperalgesiaDRG neuronsFiber lossPain disordersSensory dysfunctionNeuropathy phenotypePain phenotypesM miceSensory neuronsHyperexcitabilityChannel Nav1.7Independent mouse lines
2018
OATP1B2 deficiency protects against paclitaxel-induced neurotoxicity
Leblanc A, Sprowl J, Alberti P, Chiorazzi A, Arnold W, Gibson A, Hong K, Pioso M, Chen M, Huang K, Chodisetty V, Costa O, Florea T, de Bruijn P, Mathijssen R, Reinbolt R, Lustberg M, Sucheston-Campbell L, Cavaletti G, Sparreboom A, Hu S. OATP1B2 deficiency protects against paclitaxel-induced neurotoxicity. Journal Of Clinical Investigation 2018, 128: 816-825. PMID: 29337310, PMCID: PMC5785270, DOI: 10.1172/jci96160.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBiomarkersCell Line, TumorGenotypeHEK293 CellsHumansHyperalgesiaInhibitory Concentration 50Liver-Specific Organic Anion Transporter 1MCF-7 CellsMiceMice, Inbred DBAMice, KnockoutMice, TransgenicOrganic Anion TransportersPaclitaxelPeripheral Nervous System DiseasesPhenotypePyrimidinesConceptsPaclitaxel-induced neurotoxicityDose-limiting peripheral neurotoxicityTyrosine kinase inhibitor nilotinibAction potential amplitudeKinase inhibitor nilotinibPeripheral neurotoxicityThermal hyperalgesiaTherapeutic managementPotential amplitudeNeurotoxicityAnticancer propertiesNoncompetitive mechanismAnticancer drugsPaclitaxelAllodyniaHyperalgesiaPotential implicationsNilotinibOatp1b2Mice
2016
Striatal-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 testsStable, synthetic analogs of diadenosine tetraphosphate inhibit rat and human P2X3 receptors and inflammatory pain
Viatchenko-Karpinski V, Novosolova N, Ishchenko Y, Azhar M, Wright M, Tsintsadze V, Kamal A, Burnashev N, Miller A, Voitenko N, Giniatullin R, Lozovaya N. Stable, synthetic analogs of diadenosine tetraphosphate inhibit rat and human P2X3 receptors and inflammatory pain. Molecular Pain 2016, 12: 1744806916637704. PMID: 27030723, PMCID: PMC4955970, DOI: 10.1177/1744806916637704.Peer-Reviewed Original ResearchConceptsInflammatory painAntinociceptive effectChronic painHigh-affinity desensitizationPeripheral sensory neuronsRat brain cellsWeak partial agonistHuman P2X3 receptorsPotent analgesic agentVivo inflammation modelsDiadenosine tetraphosphateWhole-cell currentsWeak partial agonismThermal hyperalgesiaP2X3 receptorsDorsal rootsPain responseSimilar inhibitory activityAnalgesic agentsBody of evidenceInflammation modelSensory neuronsBrain cellsP2X3RsPain
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 edema
2011
Rac1-regulated dendritic spine remodeling contributes to neuropathic pain after peripheral nerve injury
Tan AM, Chang YW, Zhao P, Hains BC, Waxman SG. Rac1-regulated dendritic spine remodeling contributes to neuropathic pain after peripheral nerve injury. Experimental Neurology 2011, 232: 222-233. PMID: 21963650, DOI: 10.1016/j.expneurol.2011.08.028.Peer-Reviewed Original ResearchConceptsDorsal horn neuronsPeripheral nerve injuryChronic constriction injuryWide dynamic range dorsal horn neuronsRange dorsal horn neuronsNerve injuryNeuropathic painDendritic spinesTactile allodyniaThermal hyperalgesiaSpine morphologyInjury-induced hyperexcitabilityNoxious peripheral stimuliSpinal cord injuryMushroom-shaped spinesDendritic spine developmentDendritic spine morphologyConstriction injuryHyperexcitable responsesCCI animalsNeuronal hyperexcitabilityIpsilateral hindNociceptive thresholdSpine densityCord injury
2008
Neuropathic Pain Memory Is Maintained by Rac1-Regulated Dendritic Spine Remodeling after Spinal Cord Injury
Tan AM, Stamboulian S, Chang YW, Zhao P, Hains AB, Waxman SG, Hains BC. Neuropathic Pain Memory Is Maintained by Rac1-Regulated Dendritic Spine Remodeling after Spinal Cord Injury. Journal Of Neuroscience 2008, 28: 13173-13183. PMID: 19052208, PMCID: PMC6671613, DOI: 10.1523/jneurosci.3142-08.2008.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsComputer SimulationDendritic SpinesDisease Models, AnimalEnzyme ActivationEnzyme InhibitorsExcitatory Postsynaptic PotentialsHyperalgesiaLearningMaleMemoryNeuralgiaNeuronal PlasticityPain MeasurementPain ThresholdPosterior Horn Cellsrac1 GTP-Binding ProteinRatsRats, Sprague-DawleySpinal Cord InjuriesSynaptic TransmissionConceptsSpinal cord injuryNeuropathic painCord injuryWide dynamic range neuronsContusion spinal cord injuryDendritic spine pathologyInjury-induced hyperexcitabilityNoxious peripheral stimuliRats 1 monthChronic neuropathic painDorsal horn neuronsDendritic spine remodelingIncreased spine densityRange neuronsSpine morphometryDH neuronsTactile allodyniaNeuronal hyperexcitabilitySCI animalsThermal hyperalgesiaSham surgerySpine densityLamina IVControl neuronsSynaptic basis
1999
Mechanical and Thermal Hyperalgesia and Ectopic Neuronal Discharge After Chronic Compression of Dorsal Root Ganglia
Song X, Hu S, Greenquist K, Zhang J, LaMotte R. Mechanical and Thermal Hyperalgesia and Ectopic Neuronal Discharge After Chronic Compression of Dorsal Root Ganglia. Journal Of Neurophysiology 1999, 82: 3347-3358. PMID: 10601466, DOI: 10.1152/jn.1999.82.6.3347.Peer-Reviewed Original ResearchConceptsDorsal root gangliaChronic compressionAcute injuryRoot gangliaPreoperative valuesPostoperative testingFoot withdrawalSpontaneous dischargeIntact sympathetic nervous systemUnmyelinated peripheral nerve fibersEctopic neuronal dischargesEctopic spontaneous dischargesSympathetic nervous systemLow back painPeripheral nerve fibersDorsal root fibersBlood-borne chemicalsExtracellular electrophysiological recordingsActive myelinated fibersCotton wispNonsurgical ratsMechanical hyperalgesiaEctopic dischargesThermal hyperalgesiaBack pain
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