Many of us are familiar with receiving Novocain at the dentist to block pain, but before the 1900s, cocaine was the inhibitory neurotransmitter used for numbing purposes. Today, without Novocain, many people would likely forego the dentist altogether. Novocain, similar to many anesthetic creams employed in the laser hair removal industry, blocks the message to the brain telling us we are in pain or have discomfort. Before we can understand signal blocking, we first need to understand how signals are relayed to the brain.
Within a neuron is sodium (Na+) and calcium (CA+) voltage-gated channels. In the case of laser hair removal, as the voltage from a laser pulse is received by the tissue, a Na+ channel is opened, allowing Na+ to flow into the neuron. As the Na+ moves in, a membrane potential is created. In other words, since Na+ has a +1 charge and Na+ is moving into the neuron, when a change in charge of +20 has accumulated, a signal, also known as an action potential, is created. The action potential travels along the axon of the nerve, moving from one Na+ channel to the next, and finally to the opposite end of the nerve where vesicles filled with a neurotransmitter such as acetylcholine (adrenaline) are waiting. The Ca2+ channels now open allowing Ca2+ to flow into the neuron as well. The calcium influx allows the vesicles full of neurotransmitters to fuse with the presynaptic membrane, dumping the Acetylcholine into the synaptic cleft where it will move to the next neuron and relay the message. Notice here that an electrical stimulation caused a chemical reaction. The +20 membrane potential coupled with the neurotransmitter chemical release makes up the electrochemical gradient that allows a signal to be sent. This process happens time and time again until the signal reaches the brain.
Numbing creams block action potential pain signals to the brain by inhibiting action potentials from occurring. The pain or discomfort from the procedure is still present and Na+ is still being released as a means of trying to message the brain; however, the numbing cream serves as an inhibitory mechanism. To block signals, another form of neurotransmitter can also be released. GABA is one of these inhibitory neurotransmitters. Here, instead of Na+ channels, Chloride channels are employed. Chloride has a –1 charge and as Cl- accumulates in the neuron, the neuron's interior becomes negatively charged. If you recall, a minimum change in charge of +20 within the neuron is needed for an action potential to propagate. An open Chloride channel will make the membrane potential more negative inside the neuron, with respect to the outside of the neuron. This negative charge makes it even harder for a signal to be relayed and actually inhibits signal transduction.
To put this into perspective, during a laser procedure, if a Na+ channel is producing a +40 membrane potential and your numbing anesthetic is causing a –30 membrane potential, you would sum these potentials, totaling +10. This does not equal the +20 membrane potential change needed to meet the action potential threshold that would cause a signal to occur and therefore pain will be blocked. Action potentials are all or nothing. You either send a message or you do not. Chloride channels do not lower pain; they block pain.
The signal sent from a neuron will not be produced indefinitely. A neuron sends a signal and then stops. Starting again from the beginning of this process, as the Na+ flows into a neuron, directed to do so by the laser voltage, the positive membrane potential accumulates. At the same time, Potassium (K+) channels also open, releasing K+ in the opposing direction, to the outside of the neuron. For every three Na+ that move in, two K+ move out. As an action potential signal is sent, the Na+ channels close, but the K+ channels stay open. You can conclude that K+ will slowly depolarize the neuron, causing the neurons interior to become more negative and the signal will stop. This should sound familiar. When the neuronal membrane was influxed with Chloride anions, the negative charge induced stopped the signal as well. Signal transduction is also unidirectional, meaning that action potential signals can only be propagated in one direction. After a neuron signals a second neuron, the first neuron is temporarily inhibited so the message cannot move backwards towards its origin.
Anesthetic numbing creams also work to muffle the nerve ending's ability to sense pain with compounds such as menthol. Our sensations of heat and cold are transduced by another form of channel. TRPV1, TRPV3 and TRPV8 are examples of temperature-gated cation (positively charged ions such as H+) channels within our bodies. TRPV1 is signaled when we are over 43 degrees Celsius, telling our brain we are hot. TRPV3 functions at 33 degrees Celsius and TRPV8 is signaled at 25 degrees Celsius or less. When menthol is rubbed on the skin, the skin's temperature has not changed, yet the TRPV8 channel is opened allowing an influx of cations to flow into the neuron and our brain is told that we are cold in this location. This sensation of cold can mask the sense of pain. Eating hot peppers containing Capsaicin works in a similar manner except pain is induced. The Capsaicin stimulates the TRPV1 channel mimicking the response of actual heat. There are even candies on the market now that employ hot and cold compounds that will first release a cooling sensation and then a false sensation of heat. These sensations are false because we are not actually burned.
Pain is an inevitable part of life, but man has come up with many ingenious ways of confusing the body to mistake or ignore pain signals. So the next time your client asks, "Is this going to hurt," you should have a whole new outlook and understanding of what pain really is and how we are able to cheat our way through it.