What Local Anesthetics Do
Definition
Local Anesthetics
- Reversibly block nerve conduction in a localized area
- Patient remains conscious throughout
- Effect confined to the region of the injection
- Function fully restored when drug dissipates
Contrast
Local vs. General Anesthetics
- Local: acts at peripheral nerve — consciousness preserved
- General: acts on brain — consciousness lost
- Local: site-specific, reversible, regional
- General: systemic, requires airway management
Sodium Channel Blockade — Step by Step
Primary Mechanism
Voltage-Gated Sodium Channel Blockade
01
Un-ionized form crosses the nerve membrane — lipid-soluble uncharged fraction diffuses through the axon membrane into the cell interior
02
Ionized form binds the inner channel — inside the axon, drug converts to charged form and binds the intracellular face of the voltage-gated sodium channel
03
Sodium influx is blocked — drug occludes the channel pore; sodium ions cannot enter; the membrane cannot depolarize
04
Action potential propagation fails — threshold for firing rises; impulse cannot travel along the blocked segment; sensation is lost
pH and Ionization — Why Infected Tissue Is Resistant
Normal Tissue (pH 7.4)
Adequate Membrane Penetration
- Significant un-ionized fraction present
- Uncharged drug crosses nerve membrane
- Converts to ionized form inside axon
- Blocks channel from intracellular side
- Reliable nerve block achieved
Infected Tissue (pH < 7.0)
Impaired Membrane Penetration
- Low pH shifts equilibrium toward ionized form
- Less un-ionized drug available to cross membrane
- Less drug reaches intracellular binding site
- Block is incomplete or fails entirely
- Clinical example: dental abscess anesthesia failure
Nerve Fiber Sensitivity — Order of Differential Block
Sensitivity Rule: Small / Unmyelinated Blocked First — Large / Myelinated Blocked Last
Differential Block Sequence
| Fiber |
Size / Myelin |
Function |
Block Order |
| Type C |
Unmyelinated, smallest |
Pain, temperature, autonomic |
First (most sensitive) |
| Type B |
Small, lightly myelinated |
Preganglionic autonomic |
Blocked early |
| Type A-delta |
Small myelinated |
Sharp pain, temperature |
Blocked early |
| Type A-beta |
Medium myelinated |
Touch, pressure, proprioception |
Blocked after pain |
| Type A-alpha |
Large myelinated |
Motor, proprioception |
Last (most resistant) |
Use-Dependent Blockade
Rapidly firing neurons spend more time in the open and inactivated channel states — the states to which local anesthetics bind with highest affinity. Pain fibers at high firing frequency accumulate blockade faster than resting motor fibers. This is why pain is blocked preferentially at clinical doses.
Recovery Sequence (Reverse of Block)
Motor function returns first (large fibers, most resistant). Touch and pressure follow. Pain and temperature return last (smallest fibers, most sensitive). A patient who can move the legs but cannot feel pinprick is in differential recovery from a spinal or epidural anesthetic.