What pain transmitter, depleted via desensitization, accounts for capsaicin's role as an analgesic?

Substance P

The well-established analgesic (pain-relieving) property of capsaicin is directly linked to its ability to modulate nerve signaling, especially through a process called desensitization following initial stimulation. When capsaicin repeatedly stimulates nerve fibers, the nerve cell becomes functionally depleted of a key neuropeptide known as Substance P. Substance P is the primary chemical messenger responsible for transmitting ongoing pain signals from the site of stimulus up to the brain. Once this transmitter is depleted from the nerve ending due to the capsaicin's action, the area becomes significantly less sensitive to subsequent pain stimuli, providing a therapeutic effect utilized in topical pain management.