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 inhibitionZIPping to Pain Relief: The Role (or Not) of PKMζ in Chronicc Pain
Price TJ, Ghosh S. ZIPping to Pain Relief: The Role (or Not) of PKMζ in Chronicc Pain. Molecular Pain 2013, 9: 1744-8069-9-6. PMID: 23433248, PMCID: PMC3621284, DOI: 10.1186/1744-8069-9-6.BooksConceptsChronic pain statesChronic painLong-term potentiationAnterior cingulate cortexPain statesPain plasticityCertain chronic pain statesRole of PKMζSpinal dorsal hornChronic pain developmentSignificant clinical problemPotential roleSuch off-target effectsPain reliefDorsal hornPain developmentCNS areasCNS regionsClinical problemNociceptor stimulationPainCingulate cortexNew targetsKey moleculesOff-target effectsBDNF 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
2012
Contribution of PKMζ-dependent and independent amplification to components of experimental neuropathic pain
King T, Qu C, Okun A, Melemedjian OK, Mandell EK, Maskaykina IY, Navratilova E, Dussor GO, Ghosh S, Price TJ, Porreca F. Contribution of PKMζ-dependent and independent amplification to components of experimental neuropathic pain. Pain 2012, 153: 1263-1273. PMID: 22482911, PMCID: PMC3358498, DOI: 10.1016/j.pain.2012.03.006.Peer-Reviewed Original ResearchConceptsRostral anterior cingulate cortexExperimental neuropathic painNeuropathic painMK-801Spontaneous painN-methyl-D-aspartate receptor blockadeSpinal nerve ligation injuryNerve ligation injurySpinal dorsal hornLong-term potentiationAnterior cingulate cortexPseudosubstrate inhibitory peptideDorsal hornReceptor blockadeTime-dependent mannerLigation injuryPain processingSingle administrationSpinal cordPainCingulate cortexFull recoveryInhibitory peptidesInhibition of PKMζIndependent mechanisms