TRPM8 Mutations Associated With Persistent Pain After Surgical Injury of Corneal Trigeminal Axons
Ghovanloo M, Effraim P, Tyagi S, Aldrich A, Cheng X, Yuan J, Schulman B, Jacobs D, Dib-Hajj S, Waxman S. TRPM8 Mutations Associated With Persistent Pain After Surgical Injury of Corneal Trigeminal Axons. Neurology Genetics 2024, 10: e200206. PMID: 39555137, PMCID: PMC11567650, DOI: 10.1212/nxg.0000000000200206.Peer-Reviewed Original ResearchLaser-assisted in situ keratomileusisPostoperative ocular painTrigeminal ganglion neuronsOcular painMultielectrode array recordingsPersistent painGanglion neuronsLaser-assisted in situ keratomileusis surgeryAxonal injuryRat trigeminal ganglion neuronsTransient receptor potential cation channelCorneal refractive surgeryMultielectrode arraysAnalysis of patientsPatch-clamp analysisGenomic analysis of patientsWild-typePatch-clamp resultsExposure to mentholRefractive surgeryHyperpolarizing directionNeuronal hyperexcitabilityPain-freeTrigeminal axonsWT channelsMolecular Pharmacology of Selective NaV1.6 and Dual NaV1.6/NaV1.2 Channel Inhibitors that Suppress Excitatory Neuronal Activity Ex Vivo
Goodchild S, Shuart N, Williams A, Ye W, Parrish R, Soriano M, Thouta S, Mezeyova J, Waldbrook M, Dean R, Focken T, Ghovanloo M, Ruben P, Scott F, Cohen C, Empfield J, Johnson J. Molecular Pharmacology of Selective NaV1.6 and Dual NaV1.6/NaV1.2 Channel Inhibitors that Suppress Excitatory Neuronal Activity Ex Vivo. ACS Chemical Neuroscience 2024, 15: 1169-1184. PMID: 38359277, PMCID: PMC10958515, DOI: 10.1021/acschemneuro.3c00757.Peer-Reviewed Original ResearchExcitatory pyramidal neuronsPyramidal neuronsNeuronal action potential firingSeizure modelsActivity of excitatory neuronsInhibition of firingAction potential firingVoltage-gated sodium channelsSuppress epileptiform activityTherapeutic safety marginActivity ex vivoNeuronal hyperexcitabilityInhibitory interneuronsChannel inhibitorsEpileptiform activityInhibitory neuronsPotential firingExcitatory neuronsAntiseizure medicationsExcitatory circuitsBrain slicesReduced excitabilityPharmacological dissectionAntiseizure medication carbamazepineSodium channels