2014
Local Translation and Retrograde Axonal Transport of CREB Regulates IL-6-Induced Nociceptive Plasticity
Melemedjian OK, Tillu DV, Moy JK, Asiedu MN, Mandell EK, Ghosh S, Dussor G, Price TJ. Local Translation and Retrograde Axonal Transport of CREB Regulates IL-6-Induced Nociceptive Plasticity. Molecular Pain 2014, 10: 1744-8069-10-45. PMID: 24993495, PMCID: PMC4091745, DOI: 10.1186/1744-8069-10-45.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonal TransportBrain-Derived Neurotrophic FactorCells, CulturedColchicineCREB-Binding ProteinDisease Models, AnimalGanglia, SpinalGene Expression RegulationInterleukin-6MaleMiceMice, Inbred ICRNociceptive PainNocodazoleProtein TransportQuinazolinonesSciatic NerveSensory Receptor CellsTubulin ModulatorsConceptsCyclic AMP response element binding proteinDorsal root gangliaInterleukin-6Retrograde axonal transportNerve growth factorHyperalgesic primingMechanical hypersensitivityAxonal transportNociceptive plasticitySensory neuronsRetrograde transportExpression of BDNFPrimary sensory neuronsExpression of CREBHr post injectionIL-6 treatmentAxonal traffickingActivity-dependent translationAMP response element binding proteinResponse element-binding proteinCREB DNA bindingIntrathecal injectionHindpaw injectionNociceptive sensitizationInflammatory model
2013
mTORC1 inhibition induces pain via IRS-1-dependent feedback activation of ERK
Melemedjian OK, Khoutorsky A, Sorge RE, Yan J, Asiedu MN, Valdez A, Ghosh S, Dussor G, Mogil JS, Sonenberg N, Price TJ. mTORC1 inhibition induces pain via IRS-1-dependent feedback activation of ERK. Pain 2013, 154: 1080-1091. PMID: 23607966, PMCID: PMC3742001, DOI: 10.1016/j.pain.2013.03.021.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDown-RegulationEnzyme ActivationFeedback, PhysiologicalInsulin Receptor Substrate ProteinsMaleMAP Kinase Signaling SystemMechanistic Target of Rapamycin Complex 1MiceMice, Inbred C57BLMice, Inbred ICRMultiprotein ComplexesPainRatsRats, Sprague-DawleySensory Receptor CellsSirolimusTOR Serine-Threonine KinasesConceptsSpontaneous painMechanical hypersensitivitySensory neuronsDevelopment of painPotential treatment optionSensory neuron sensitizationRapamycin complex 1 (mTORC1) inhibitorsExtracellular signal-regulated kinase (ERK) pathwaySignal-regulated kinase pathwaySuppression of S6K1Chronic treatmentPain conditionsPain therapeuticsTransplant rejectionAdenosine monophosphate-activated protein kinase (AMPK) activatorProtein kinase activatorsTreatment optionsAntidiabetic drugsPainSensory hypersensitivityMTOR pathwayNegative feedback loopCertain cancersMammalian targetMTORC1 inhibitionBDNF Regulates Atypical PKC at Spinal Synapses to Initiate and Maintain a Centralized Chronic Pain State
Melemedjian OK, Tillu DV, Asiedu MN, Mandell EK, Moy JK, Blute VM, Taylor CJ, Ghosh S, Price TJ. BDNF Regulates Atypical PKC at Spinal Synapses to Initiate and Maintain a Centralized Chronic Pain State. Molecular Pain 2013, 9: 1744-8069-9-12. PMID: 23510079, PMCID: PMC3608966, DOI: 10.1186/1744-8069-9-12.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain-Derived Neurotrophic FactorCalcium-Calmodulin-Dependent Protein Kinase Type 2Cerebral CortexChronic PainEukaryotic Initiation Factor-4FExtracellular Signal-Regulated MAP KinasesMaleMAP Kinase Signaling SystemMiceMice, Inbred ICRMitogen-Activated Protein Kinase KinasesModels, BiologicalPhosphorylationPosterior Horn CellsProtein BiosynthesisProtein Kinase CProtein TransportSynapsesTime FactorsTOR Serine-Threonine KinasesConceptsChronic pain statesPain statesPersistent nociceptive sensitizationSpinal synapsesChronic painNociceptive sensitizationPotential therapeutic targetImportant medical problemNeurotrophic factorBDNF regulationPersistent sensitizationBDNFTherapeutic targetMedical problemsPainNovel therapeuticsEssential mediatorSensitizationPermanent reversalSynapsesMolecular linkPKMζKey regulator
2011
Spinal Protein Kinase M ζ Underlies the Maintenance Mechanism of Persistent Nociceptive Sensitization
Asiedu MN, Tillu DV, Melemedjian OK, Shy A, Sanoja R, Bodell B, Ghosh S, Porreca F, Price TJ. Spinal Protein Kinase M ζ Underlies the Maintenance Mechanism of Persistent Nociceptive Sensitization. Journal Of Neuroscience 2011, 31: 6646-6653. PMID: 21543593, PMCID: PMC3090264, DOI: 10.1523/jneurosci.6286-10.2011.Peer-Reviewed Original ResearchConceptsLate long-term potentiationInterleukin-6Intraplantar injectionPersistent nociceptive sensitizationIntrathecal injectionNociceptive sensitizationResolution of hypersensitivitySpinal dorsal hornClinical pain disordersProtein kinase M ζLong-term potentiationAllodynic statePlantar incisionDorsal hornPain pathwaysPain statesAgonist injectionPain disordersAgonist DHPGNocifensive behaviorNocifensive responsesPKMζ inhibitorSpinal cordAllodyniaTherapeutic benefit