Local anesthetic agents are functionally divided into the amino amide and amino ester groups (Fig. 1). Both groups share a similar chemical structure that contains three components: a hydrophilic amine portion, an intermediate chain, and a lypophilic aromatic ring. The intermediate chain contains either an ester or amide linkage which categorizes the agent.

Pain sensation is carried via C fiber (unmyelinated nerve, 0.5–1 μm) and A-delta fiber (2–5 μm). These fibers are more sensitive to the actions of local anesthetics as compared to large nerve fibers. Consequently, patients may be able to feel sensations such as pressure and vibration while being insensitive to pain.

The effectiveness of a local anesthetic depends on its ability to diffuse across the nerve cell’s membrane (lipophilic properties) and then convert to a cationic form that results in better protein binding (hydrophilic properties). Higher lipid solubility of an agent increases its diffusion through a cell’s membrane, leading to higher potency and lower concentrations needed to produce the desired result. However, greater protein-binding ability leads to a longer duration of action due to a higher affinity for intracellular receptors.

Most local anesthetics except cocaine have vasodilatory effects, which increases chances of excessive bleeding during the course of the procedure. To counteract this, epinephrine is often added as a vasoconstrictive agent, which has the added benefit of increasing the local sequestration of the anesthetic, minimizing systemic effects and increasing the length of anesthetic effect.

Topically-applied anesthetic agents are suitable for use in superficial laser surgery and minor dermatological procedures. Topical anesthetics act by disrupting sodium channel activity and blocking electrical impulse transmission at nerve endings. They can also be used to permit painless needle insertion when infiltrative anesthesia is required. These agents are usually encountered in an oil-in-water base or similar cream compound. For quick procedures, cooling sprays such as dichlorotetrafluoroethane or ethylchloride may be used.

The skin’s stratum corneum serves as a mechanical barrier slowing down topical anesthesia penetration. Thus, the vehicle is very important in helping the anesthetic traverse the epidermis. The thickness of the stratum corneum varies with anatomical locations, altering the time to achieve adequate anesthesia. Occlusion with a plastic wrap is one way of enhancing product penetration and delivery to the dermis. This method also hydrates the skin, which may help explain the lower incidence of side effects seen after its use in carbon dioxide resurfacing laser procedures.

The most widely used topical anesthetic is EMLA cream, a 5% eutectic mixture of lidocaine 2.5% and prilocaine 2.5% in an oil-in-water emulsion. It must be applied under an occlusive dermal dressing for 60 min for adequate dermal anesthesia. EMLA has been shown to provide adequate anesthesia for pulsed dye laser treatments of Port Wine Stains (PWSs) without affecting the laser treatment’s efficacy. It is also used in ablative laser resurfacing. The major concern regarding the use of EMLA relates to the potential risk of methemoglobinemia, also a known side effect of prilocaine. It is more likely in neonates, especially in pre-term infant.

LMX-4 (formerly called ELA-Max) is a 4% lidocaine cream in a liposomal vehicle that only requires 15–45 min of application time without the need of an occlusive dressing following its application. LMX-5 is the 5% concentration and although it is marketed for anorectal use, it can also be applied as a topical anesthetic agent.

Betacaine-LA ointment contains lidocaine, prilocaine and a vasoconstrictor in a liquid paraffin ointment. It has a recommended application time of 30–45 min without the requirement of an occlusive dressing.

Tetracaine gel is a long-acting ester anesthetic composed of 4% tetracaine in a lecithin gel. Its time application is 30 min under an occlusive dressing.

The 7% lidocaine and 7% tetracaine (LT) peel is a self occlusive topical anesthetic, presenting as a 1:1 eutectic mixture that is applied as a cream and air-dries to form a flexible membrane that can be peeled from the skin. The recommended application time is 30 min. LT peel has been successfully used in a variety of dermatological procedures such as PDL therapy, laser-assisted hair removal, non-ablative facial laser resurfacing, laser therapy for leg veins, cutaneous laser resurfacing and laser-assisted tattoo removal. It has shown to have a superior anesthetic efficacy in adult patients undergoing a variety of cutaneous procedures when compared to EMLA cream.

Quick procedures that require only a few seconds of anesthesia can utilize cooling refrigerant sprays, such as dichlorotetrafluoroethane or ethyl chloride. Ice cubes can also be used, especially to give painless injections in children.

Infiltrative anesthesia is the most commonly performed form of skin anesthesia. The concentration and selection of infiltrative anesthetics depend on the procedure to be performed, the speed of onset desired, and duration of action required. For quick and simple procedures, a short-acting anesthetic with rapid onset can be chosen. As for larger procedures, longer-acting agents will be needed.

When an extensive area of the skin is to be anesthetized, the anesthetic should be diluted in order to limit the total amount applied to the tissue and to reduce possible systemic adverse reactions. Conversely, higher concentrations can be used in smaller quantities for specific nerve blocks.

The ester-linked anesthetics (i.e. procaine, cocaine, tetracaine) have decreased in popularity due to allergic and cross-reactions with benzocaine, para-aminobenzoic acid (PABA), paraphenylenediamine, and sulfonamides.

Most procedures are performed using 1% or 2% lidocaine providing quick onset, long duration (45 min to 3 h without epinephrine), and low allergic reaction potential. When combined with epinephrine, an even longer anesthetic response can be achieved.