The Expression of P2X Purinoreceptors in Sensory Neurons: Effects of Axotomy and Glial-Derived Neurotrophic Factor

We have studied the distribution and regulation of the P2X sub(3) receptor (a ligand-gated ion channel activated by ATP) in adult dorsal root ganglion (DRG) neurons using a polyclonal antibody. P2X sub(3) receptor immunoreactivity was normally present in about 35% of L4/5 DRG neurons, virtually all small in diameter. In the dorsal horn, P2X sub(3) receptor expression was restricted to the terminals of sensory neurons terminating in lamina IIinner. P2X sub(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 sub(3) receptors were found mostly in sensory neurons that bind the lectin IB4. After sciatic nerve axotomy, P2X sub(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 sub(3) receptor. We conclude that P2X sub(3) receptors are normally expressed in nociceptive primary sensory neurons, predominantly the nonpeptidergic nociceptors. P2X sub(3) receptors are down-regulated following peripheral nerve injury and their expression can be regulated by GDNF.