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How does histamine in stinging nettles cause itching and swelling?

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antihistamines, including Benadryl — antihistamine Antihistamines such as Benadryl (diphenhydramine) and Claritin (loratadine) can be purchased without prescriptions. Both of those agents act by blocking H₁ receptors. However, whereas Benadryl binds to those receptors in the central nervous system (CNS), causing drowsiness, Claritin does not readily enter the CNS and thus does not normally cause drowsiness.

Stinging nettles (Urtica dioica) possess specialized, hair-like structures called trichomes that function as a defense mechanism. These structures have bulbous tips that break upon contact, exposing needlelike tubes that pierce the skin and inject a chemical cocktail containing histamine, acetylcholine, serotonin, and formic acid.1

The histamine injected by the plant is directly responsible for the resulting itching and swelling. In the body, histamine acts by binding to specific receptors on cell surfaces, which triggers the dilation of blood vessels and increases their permeability. This vascular response allows fluids and immune cells to leak from the bloodstream into the surrounding tissue, leading to the localized swelling and irritation characteristic of a nettle sting.2