The expression of P2X3 purinoreceptors in sensory neurons:: Effects of axotomy and glial-derived neurotrophic factor

We have studied the distribution and regulation of the P2X(3) receptor (a ligand-gated ion channel activated by ATP) in adult dorsal root ganglion (DRG) neurons using a polyclonal antibody. P2X(3) receptor immunoreactivity was normally present in about 35% of L4/5 DRG neurons, virtually all small in diameter. In the dorsal horn, P2X(3) receptor expression was restricted to the terminals of sensory neurons terminating in lamina llinner. P2X(3) receptors were expressed in approximately equal numbers of sensory neurons projecting to skin and viscera but in very few of those innervating skeletal muscle. P2X(3) receptors were found mostly in sensory neurons that bind the lectin IB4. After sciatic nerve axotomy, P2X(3) receptor expression dropped by more than 50% in L4/5 DRG. Glial cell line-derived neurotrophic factor (GDNF), delivered intrathecally, completely reversed axotomy-induced down-regulation of the P2X(3) receptor. We conclude that P2X(3) receptors are normally expressed in nociceptive primary sensory neurons, predominantly the nonpeptidergic nociceptors. P2X(3) receptors are down-regulated following peripheral nerve injury and their expression can be regulated by GDNF.