THIS IS HOW LOCAL ANAESTHESIA WORKS
Lying on my back in the emergency room with a sliced open finger last night, I looked up to the bright white lights shining onto my throbbing hand, so many thoughts cutting into my brain. Why hadn't whatever fell from the shelf landed on my face?. I could have taken a scar, but would this affect my plan to become a surgeon? Who put animal stickers on the light above me? Just how much experience did this doctor have giving stitches? Where did he buy the large metallic turtle necklace he had on? And just how did anaesthesia work?
It shocked me really, I had expected not to feel anything after the 3ml of fluid was injected into my now-triple-the-normal-size finger, but I could still feel it and it took a while to register that in fact it wasn't pain I was feeling, it was something I'd describe as uncomfortable awareness of my finger.
Not that I'd ever really stopped to consider it, but it was just one of those things that you assume without really knowing why or how you did in the first place: you don't feel anything under local anaesthetic. Clearly, this wasn't the case.
What is local anaesthesia?
A local anaesthetic is a drug that, when injected, produces a state of local anaesthesia by reversibly blocking the nerve conductances that transmit the feeling of pain from the point of administration to the brain.
Peripheral nerves, through conduction between one another, transmit a pain signal from the site of injury to the brain, which processes the feeling and conscious awareness of pain. Local anaesthetics interfere with this conduction. When there has been an injury to the skin, specialised nerve endings are activated, starting an action potential which travels up the nerve cell. Normally, when this electric signal is above its threshold action potential, it can propagate along the length of the axon, opening sodium channels, to allow the influx of sodium ions into the cell, carrying the electric signal across the cell and along to the next, all the way to the brain.
Local anaesthetics are membrane-stabilizing drugs; they reversibly decrease the rate of depolarization and repolarization of excitable membranes.
Local anaesthetic itself is a weak base, in its hydrochloride salt form to be water soluble. When in water, a weak base forms an equilibrium between its two forms: protonated-when it has a hydrogen ion from water attached to it and unprotonated-when it doesn't have a hydrogen ion attached. The unprotonated form is uncharged, so it readily passes through the plasma membrane (charged molecules cannot easily diffuse through the plasma membrane). Once on the other side, some of the uncharged molecules become charged, forming an equilibrium again. They now cannot diffuse back across the plasma membrane, this is called "ion-trapping". It is these charged protonated forms of the local anaesthetic molecule which can bind to the sodium channels.
Acidosis, which may occur due to inflammation at the site of the wound therefore reduces the effect of local anaesthetic, because most of it would be in its ionised form, unable to cross the plasma membrane.
What are sodium channels?
The way that a cell propagates an action potential is through sodium channels. Action potentials travel along a neuron as an electrochemical cascade, through a net inflow of positively charged ions into the cell. Sodium channels are arrangements of protein imbedded in the plasma membrane of neuron cells. Opening to allow positively charged sodium ions to enter the cell through them, this is how sodium channels create depolarisation and action potentials.
The sodium channels consist of various subunits, and 4 domains. The S6 segment of domain IV has been proposed to contain the receptor for local anaesthetics, which block Na+ channels in a voltage-dependent manner (Ragsdale et al. 1994).
How does local anaesthesia affect a sodium channel?
As seen in part A above, when an electrical signal propagates along the membrane of an axon, the sodium channels in part B open, allowing the influx of sodium into the cell. In the presence of a local anaesthetic, shown as a red dot in the picture, the anaesthetic moves to the inside of the cell, binding to the sodium channel. This blocks the influx of sodium ions, stopping conductance and signals reaching the brain. Local anaesthesia binds much more readily with sodium channels in an activated state, working faster in rapidly firing neutrons, known as state-dependent blockade.
Why can I still feel my finger?
After learning all this, I still have a question: if an anaesthetic works by attaching to a sodium channel, does it somehow distinguish between neurons that transmit pain and sensory neurons? Why can't I feel pain but I can feel and move my finger? Are the sodium channels somehow different in different neurons?
It turns out that all neurons are sensitive to local anaesthetics, but they have different myelination and diameters, which makes them have different sensitivities to local anaesthetics: differential blockade. There is an order of sensitivity: Type B fibers (sympathetic tone) are the most sensitive followed by type C (pain), type A delta (temperature), type A gamma (proprioception), type A beta (sensory touch and pressure), and type A alpha (motor). This is why pain is the first thing to go, and movement the last!