*LA blocks voltage gated NA+ channels. The unionized form of the LA diffuses through the nerve axon into the axolemma. A lower pH inside the neuron/axolemma causes nonionized portion to split into ionized/unionized portions; the ionized portion binds to a receptor on the sodium channel when the channel is in the inactivated state. When the sodium channel is inactivated, action potentials cannot be generated.
*2-3 nodes of Ranvier must be blocked to stop nerve conduction
*Conduction block is frequency dependent=>the greater the frequency of action potentials, the faster the nerve is blocked by LA and LA must attach to sodium channel when it is in the inactivated/closed (yet open)/absolute refractory state, thus the faster the nerve fires, the more opportunities for LA to catch the sodium channel in inactivated state and sensory fibers fire at greater frequency than motor fibers thus more likely to be blocked; both unionized and ionized forms of the LA are required for conduction block.
*Local anesthetics, once bound to the inside of the voltage-gated sodium channel, stabilize and prolong the duration of the inactivated state, thus inhibiting VGSC opening during further depolarization. This inhibits neuronal conduction.