Pruriceptors

Pruriceptors are a subset of sensory nerve fibers in the skin specialized for detecting itch. They are primarily unmyelinated C-fibers, with some A-delta fibers, whose free nerve endings reside in the epidermis and dermis. When activated, pruriceptors transmit signals to the spinal cord and brain that are perceived as itch, prompting scratching as a defensive response to remove irritants.

Pruriceptors respond to a range of pruritic mediators. Histamine, released during allergic reactions, can activate itch fibers via histamine receptors such as H1 and, to a lesser extent, H4. Nonhistaminergic itch involves other mediators including proteases acting on protease-activated receptors (PAR-2), cytokines like interleukin-31, and various peptides. In animal models, a family of mas-related G protein-coupled receptors (Mrgprs) has been linked to nonhistaminergic itch, with receptor subtypes that may be involved in mediating certain pruritic stimuli. The transduction of itch signals also relies on ion channels such as TRPV1 and TRPA1, which help convert receptor activation into electrical signals in the nerve fibers.

Central processing of pruriceptor signals begins in the dorsal root ganglia and spinal cord, where primary afferents synapse with second-order neurons. The itch signal is then relayed to higher brain centers, including the thalamus and somatosensory cortex, with contributions from interneuronal circuits that modulate perception. GRP and its receptor GRPR have been implicated in a spinal itch pathway, while descending systems and endogenous opioids can influence itch perception.

Clinically, pruriceptors are central to chronic itch conditions such as atopic dermatitis, where peripheral sensitization and cross-talk with immune cells amplify itch. Therapeutic approaches target histamine pathways, cytokines like IL-31, PARs, or Mrgpr-related mechanisms, reflecting the diverse biology of pruriception.