P2X receptors in sensory neurones

P2X receptors are a family of ligand-gated ion channels responsive to ATP. Seven subtypes have been identified which form homomultimeric or heteromultimeric pores. P2X(3) receptors are selectively expressed predominantly on small-diameter nociceptive sensory neurones in the dorsal root, trigeminal and nodose ganglia, particularly the non-peptidergic subpopulations labelled with the lectin IB4. P2X(2/3) labelling is also present in inner lamina II of the spinal cord and in sensory nerve projections to skin and viscera, but few receptors are present in skeletal muscle. P2X(3) receptors are down-regulated after peripheral nerve injury and their expression can be regulated by glial cell-derived neurotrophic factor. P2X receptor activation of sensory neurones has been demonstrated in in vivo pain models, including the rat hindpaw and knee-joint preparations, as well as in inflammatory models. P2X(4) and/or P2X(6) receptors in the CNS also seem to be involved in pain pathways. Non-nociceptive P2 receptors on sensory nerves are present in muscle and on sensory endings in the heart and lung that initiate reflex activity involving vagal afferent and efferent nerve fibres. The sources of ATP involved in nociception and non-nociceptive sensory nerve stimulation are discussed as well as a novel hypothesis about purinergic mechanosensory transduction.