2023
Lessons learned in translating pain knowledge into practice
Becker J, Effraim P, Dib-Hajj S, Rittner H. Lessons learned in translating pain knowledge into practice. PAIN Reports 2023, 8: e1100. PMID: 37928204, PMCID: PMC10624476, DOI: 10.1097/pr9.0000000000001100.Peer-Reviewed Original ResearchPain knowledgeCalcitonin gene-related peptide antagonistsGrowth factorNovel pain treatmentsClinical phase IISevere side effectsMechanisms of nociceptionBetter preclinical modelsNeuronal growth factorsHands of cliniciansLack of effectMore patientsMusculoskeletal painPain treatmentChronic painClinical updateNew analgesicsClinical trialsNeurokinin receptorsPreclinical modelsPreclinical studiesSide effectsPatientsJoint replacementAvailable evidenceTRPA1 rare variants in chronic neuropathic and nociplastic pain patients
Marchi M, Salvi E, Andelic M, Mehmeti E, D'Amato I, Cazzato D, Chiappori F, Lombardi R, Cartelli D, Devigili G, Bella E, Gerrits M, Almomani R, Malik R, Ślęczkowska M, Mazzeo A, Gentile L, Dib-Hajj S, Waxman S, Faber C, Vecchio E, de Tommaso M, Lauria G. TRPA1 rare variants in chronic neuropathic and nociplastic pain patients. Pain 2023, 164: 2048-2059. PMID: 37079850, PMCID: PMC10443199, DOI: 10.1097/j.pain.0000000000002905.Peer-Reviewed Original ResearchConceptsNociplastic painPainful neuropathyPain patientsHealthy controlsRare variantsChronic neuropathic painChronic pain disordersChronic widespread painChronic pain patientsMolecular profilePainless neuropathyNeuropathic painPain disordersWidespread painChronic painPatient's molecular profileIndependent cohortPainPatientsClinical diagnosisDisease riskNeuropathyTRPA1 variantsNew risk genesPain genesConserved but not critical: Trafficking and function of NaV1.7 are independent of highly conserved polybasic motifs
Tyagi S, Sarveswaran N, Higerd-Rusli G, Liu S, Dib-Hajj F, Waxman S, Dib-Hajj S. Conserved but not critical: Trafficking and function of NaV1.7 are independent of highly conserved polybasic motifs. Frontiers In Molecular Neuroscience 2023, 16: 1161028. PMID: 37008789, PMCID: PMC10060856, DOI: 10.3389/fnmol.2023.1161028.Peer-Reviewed Original ResearchSensory axonsPeripheral voltage-gated sodium channelsMajor unmet clinical needFunction of Nav1.7Non-addictive treatmentsUnmet clinical needVoltage-clamp recordingsVoltage-gated sodium channelsPain therapyChronic painPrimary afferentsNoxious stimuliTherapeutic modalitiesAction potentialsAxonal transportClinical needVesicular packagingSodium channelsHuman painPainAxonal traffickingAxonal surfaceAxonal membraneAxonsAttractive target
2017
Reverse pharmacogenomics: carbamazepine normalizes activation and attenuates thermal hyperexcitability of sensory neurons due to Nav1.7 mutation I234T
Yang Y, Adi T, Effraim PR, Chen L, Dib‐Hajj S, Waxman SG. Reverse pharmacogenomics: carbamazepine normalizes activation and attenuates thermal hyperexcitability of sensory neurons due to Nav1.7 mutation I234T. British Journal Of Pharmacology 2017, 175: 2261-2271. PMID: 28658526, PMCID: PMC5980548, DOI: 10.1111/bph.13935.Peer-Reviewed Original ResearchConceptsUse-dependent inhibitionSensory neuronsDorsal root ganglion sensory neuronsIntact sensory neuronsDRG sensory neuronsMulti-electrode array recordingsTreatment of painTargeting Ion ChannelsEffects of carbamazepineMutant channelsT mutationChronic painActivation of NaSodium channel variantsSection visitPainPharmacogenomic approachPharmacological analysisPatch clampPatientsNeuronsHigher firingCarbamazepineThemed sectionChannel variants
2016
Pharmacotherapy for Pain in a Family With Inherited Erythromelalgia Guided by Genomic Analysis and Functional Profiling
Geha P, Yang Y, Estacion M, Schulman BR, Tokuno H, Apkarian AV, Dib-Hajj SD, Waxman SG. Pharmacotherapy for Pain in a Family With Inherited Erythromelalgia Guided by Genomic Analysis and Functional Profiling. JAMA Neurology 2016, 73: 659. PMID: 27088781, DOI: 10.1001/jamaneurol.2016.0389.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAdultAnalgesics, Non-NarcoticBrainCarbamazepineChronic PainDNA Mutational AnalysisDouble-Blind MethodElectric StimulationErythromelalgiaFemaleGanglia, SpinalHumansMagnetic Resonance ImagingMaleMutationNAV1.7 Voltage-Gated Sodium ChannelPain MeasurementRegression AnalysisSensory Receptor CellsConceptsMean episode durationDRG neuronsPatient 1Nav1.7 mutationEpisode durationDorsal root ganglion neuronsPlacebo-controlled studyMaintenance periodAttenuation of painEffects of carbamazepineBrain activityFunctional magnetic resonance imagingMagnetic resonance imagingT mutationMutant channelsFunctional magnetic resonanceNeuropathic painSecondary somatosensoryChronic painPain areaPatient 2Ganglion neuronsEffective pharmacotherapyNight awakeningsPlacebo
2009
Voltage-Gated Sodium Channels: Therapeutic Targets for Pain
Dib-Hajj S, Black JA, Waxman SG. Voltage-Gated Sodium Channels: Therapeutic Targets for Pain. Pain Medicine 2009, 10: 1260-1269. PMID: 19818036, DOI: 10.1111/j.1526-4637.2009.00719.x.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsDifferent pain statesPain statesVoltage-gated sodium channelsPain syndromeTherapeutic targetParoxysmal extreme pain disorderFunction mutationsIsoform-specific blockersSodium channelsInflammatory pain conditionsDifferent pain syndromesTreatment of painDorsal root gangliaSodium channel expressionMajor medical needsSodium channel blockersSodium channel isoformsAmeliorate painPain conditionsPain disordersChronic painTreatment optionsRoot gangliaNociceptor neuronsChannel blockers
2005
Erythromelalgia: A hereditary pain syndrome enters the molecular era
Waxman SG, Dib‐Hajj S. Erythromelalgia: A hereditary pain syndrome enters the molecular era. Annals Of Neurology 2005, 57: 785-788. PMID: 15929046, DOI: 10.1002/ana.20511.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsPain syndromeGanglion neuronsCentral nervous system neuronsDorsal root ganglion neuronsChronic neuropathic painSodium channelsSympathetic ganglion neuronsIon channel mutationsChannel functionSodium channel functionAutosomal dominant disorderNeuropathic painPain disordersChronic painAltered excitabilityModerate exerciseSystem neuronsPrimary erythermalgiaRational therapyErythromelalgiaPainFirst human disorderModel diseaseWarm stimuliSyndrome
2001
Diverse Functions and Dynamic Expression of Neuronal Sodium Channels
Waxman SG, Cummins TR, Black JA, Dib‐Hajj S. Diverse Functions and Dynamic Expression of Neuronal Sodium Channels. Novartis Foundation Symposia 2001, 241: 34-60. PMID: 11771649, DOI: 10.1002/0470846682.ch4.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsChannel gene expressionNervous systemChannel expressionNormal nervous systemTypes of neuronsNeuronal sodium channelsChannel genesChronic painGene expressionMultiple sclerosisPeripheral axonsChannel subtypesMaladaptive changesPathological neuronsNeuronal functionPurkinje cellsTherapeutic opportunitiesExperimental modelAmino acid sequenceSodium channelsNa channelsNeuronsDifferent amino acid sequencesRecent evidenceSelective modulators
2000
Sodium channels and the molecular pathophysiology of pain
Cummins T, Dib-Hajj S, Black J, Waxman S. Sodium channels and the molecular pathophysiology of pain. Progress In Brain Research 2000, 129: 3-19. PMID: 11098678, DOI: 10.1016/s0079-6123(00)29002-x.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsDorsal root gangliaTrigeminal neuronsSodium channelsAction potentialsDorsal root ganglion neuronsSpontaneous action potential activityMolecular pathophysiologyPrimary sensory neuronsPeripheral target tissuesAction potential activitySodium channel expressionChain of neuronsPathological burstingNerve injuryNociceptive pathwaysChronic painGanglion neuronsRoot gangliaSensory neuronsChannel expressionSomatosensory systemPainNeuronsTarget tissuesPathophysiology
1998
SNS Na+ channel expression increases in dorsal root ganglion neurons in the carrageenan inflammatory pain model
Tanaka M, Cummins T, Ishikawa K, Dib-Hajj S, Black J, Waxman S. SNS Na+ channel expression increases in dorsal root ganglion neurons in the carrageenan inflammatory pain model. Neuroreport 1998, 9: 967-972. PMID: 9601651, DOI: 10.1097/00001756-199804200-00003.Peer-Reviewed Original ResearchConceptsSmall DRG neuronsDorsal root ganglion neuronsInjection of carrageenanDRG neuronsInflamed limbGanglion neuronsSodium currentTTX-R sodium currentsTetrodotoxin-resistant sodium currentInflammatory pain modelDevelopment of hyperexcitabilitySodium channel expressionPatch-clamp recordingsInflammatory painPain modelChronic painCarrageenan injectionNociceptive cellsContralateral sideNaive ratsChannel expressionProjection fieldsMRNA expressionNeuronsSodium channels