Local anaesthetics block the initiation and propagation of the pain signal through the nociceptive neuron towards the dorsal horn.They inhibit the transmission of action potentials by blocking the voltage dependent sodium-channels. To achieve this, the local anaesthetic needs to pass the nerve sheath and the axon membrane before it can bind to the intracellular site of the sodium-channel.
Local anaesthetic activity is strongly dependent on the pH of the local environment: in an alkaline pH they exert their best action. In order to be able to pass the axon membrane, the local anaesthetic requires transformation into a lipophilic alkaline form.
The pH-dependence is of great clinical importance, since sites of inflammation are usually acidic and thus resistant to local anaesthetics. High doses can cause deregulation of organ systems, such as the heart and the central nervous system by disturbing their neuronal control.
Small diameter axons are more susceptible to local anaesthetics than large axons.
Local anaesthetics are injected with an acidic solvent.
Local anaesthetics do NOT block the activity of motor neurons.