Voltage-gated sodium channels (Nav) on sensory nerve membranes

Class

Ester-type local anesthetic (topical ophthalmic gel, chloroprocaine hydrochloride 3%; brand IHEEZO) — used for ocular-surface anesthesia, e.g. prior to intravitreal anti-VEGF/complement injections; not itself a disease-modifying AMD therapy

Pathway

Reversible blockade of voltage-gated sodium channels prevents depolarization and nerve-impulse conduction (local anesthesia), unrelated to angiogenic or complement signaling

Voltage-gated sodium (Nav) channels are membrane proteins found on nerve fibers, including the sensory nerves that transmit pain and touch signals from the ocular surface. Normal nerve signaling depends on a rapid influx of sodium ions through these channels, which generates the electrical impulse (action potential) that travels along the nerve to the brain. Local anesthetics work by binding to Nav channels from inside the nerve cell membrane and stabilizing them in a non-conducting state, preventing sodium influx and thereby blocking impulse conduction. Because the effect is confined to the nerves exposed to the drug and reverses as the drug diffuses away or is metabolized, this mechanism produces temporary, localized numbness rather than a systemic effect. In ophthalmology, this principle is applied topically to anesthetize the ocular surface before procedures that would otherwise cause discomfort, such as intraocular injections. This mechanism is unrelated to the disease processes being treated by those injections; it is purely a supportive measure to enable a painless procedure. The same channel-blocking principle underlies local anesthesia across many fields of medicine, from dentistry to minor surgery, wherever reversible, localized interruption of nerve signaling is desired.