2024
Functionally-selective inhibition of threshold sodium currents and excitability in dorsal root ganglion neurons by cannabinol
Ghovanloo M, Effraim P, Tyagi S, Zhao P, Dib-Hajj S, Waxman S. Functionally-selective inhibition of threshold sodium currents and excitability in dorsal root ganglion neurons by cannabinol. Communications Biology 2024, 7: 120. PMID: 38263462, PMCID: PMC10805714, DOI: 10.1038/s42003-024-05781-x.Peer-Reviewed Original ResearchConceptsDorsal root ganglionDorsal root ganglion neuronal excitabilityDorsal root ganglion neuronsNeuronal excitabilityCurrent-clamp analysisSteady-state inactivationVoltage-dependent sodiumSlow inactivated stateAutomated patch clamp platformMultielectrode array recordingsNav currentsNeuropathic painSodium currentRoot ganglionGanglion neuronsSlow inactivationInactivated stateCurrent inhibitorsIon channelsNeuronsInhibitory effectCannabinolArray recordingsEndocannabinoidCannabinoid
2022
Inhibition of sodium conductance by cannabigerol contributes to a reduction of dorsal root ganglion neuron excitability
Ghovanloo M, Estacion M, Higerd‐Rusli G, Zhao P, Dib‐Hajj S, Waxman SG. Inhibition of sodium conductance by cannabigerol contributes to a reduction of dorsal root ganglion neuron excitability. British Journal Of Pharmacology 2022, 179: 4010-4030. PMID: 35297036, DOI: 10.1111/bph.15833.Peer-Reviewed Original ResearchConceptsEffect of cannabigerolDRG neuronsDorsal root ganglion neuron excitabilityVoltage-gated sodium currentDorsal root ganglion neuronsLower CBG concentrationPrimary dorsal root ganglion neuronsAnalgesic drug developmentNon-psychotropic phytocannabinoidMultielectrode array recordingsAction potential modellingInhibition of NaDRG excitabilityGanglion neuronsNeuron excitabilityAnalgesic propertiesCNS neuronsNeuronal hypoexcitabilityCBG concentrationsChannel inhibitorsSodium currentNeuronsFunctional selectivityDrug developmentUnderlying mechanism
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