P2 purinergic signaling and pruritus.

Pruritus is a common sensation that triggers scratching. Extracellular nucleotides and nucleosides, along with their receptors, primarily compose the purinergic signaling. The purinergic signaling mechanism in itch remains incompletely understood. Keratinocytes, fibroblasts, Langerhans cells, primary sensory nerve endings in the skin, and neurons and satellite glial cells in primary sensory ganglia (dorsal root ganglia and trigeminal ganglia) have been confirmed to express multiple subtypes of P2X and P2Y receptors. Purinergic signaling in the skin and primary sensory ganglia is involved in the pathological changes of skin pruritus, including atopic dermatitis, psoriasis, systemic sclerosis, diabetes complicated with pruritus, or other pruritus disorders. The interaction between P2 purinergic signaling and histamine receptors, transient receptor potential (TRP) channel receptors, and Mas-related G protein-coupled receptor member A3 (MrgprA3) receptors, which mediate itch signaling, is involved in the pathological process of skin pruritus. P2 purinergic receptor agonists can induce itching behaviors in animals. Targeted antagonism or inhibition of P2 purinergic receptors in the skin and primary sensory ganglia can alleviate pathological changes in skin pruritus. This review summarizes studies concluding that P2 receptors are involved in the pathogenesis of pruritus, with several showing potential as novel therapeutic options for alleviating pruritus.