pruriception

Pruriception is the sensory process by which itch is perceived. It begins with the activation of specialized peripheral nerve fibers, called pruriceptors, in the skin. These fibers are mainly unmyelinated C-fibers and, to a lesser extent, thinly myelinated fibers, which transduce itch-evoking stimuli into electrical signals that travel toward the central nervous system.

Peripheral mediators that can trigger pruriception include histamine released from mast cells, which acts on histamine receptors (notably H1 and H4) on nerve endings. However, many itch sensations are histamine-independent and arise from other mediators such as protease-activated receptor-2 (PAR-2) signaling, certain peptide transmitters, cytokines like interleukin-31 (IL-31), endothelin-1, bile acids, and other pruritogens. In animals, various receptor families, including mas-related G protein–coupled receptors (Mrgprs), contribute to non-histaminergic itch; similar mechanisms are being explored in humans.

Central processing involves transmission of pruriceptive signals to the spinal cord, where specific dorsal horn neurons relay the information to higher brain centers. In the spinal cord, certain itch circuits involve gastrin-releasing peptide (GRP) and its receptor (GRPR), among other pathways. Supraspinal processing in the thalamus and cerebral cortex integrates itch with attention and emotional response, and the act of scratching provides relief through sensory interactions that modulate these circuits.

Clinically, itch is a common symptom in dermatologic and systemic diseases and can be acute or chronic (lasting longer than six weeks). Assessment uses patient-reported scales of intensity. Treatments focus on the underlying cause and may include antihistamines for histaminergic itch, gabapentinoids for neuropathic itch, topical therapies, phototherapy, and targeted biologics or receptor antagonists (e.g., NK1 antagonists, anti–IL-31 therapies) for certain chronic pruritides.