THE EXPRESSION OF P2X(3) PURINORECEPTORS IN SENSORY NEURONS - EFFECTSOF 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 ga nglion (DRG) neurons using a polyclonal antibody. P2X(3) receptor immu noreactivity was normally present in about 35% of L4/5 DRG neurons, vi rtually all small in diameter. In the dorsal horn, P2X(3) receptor exp ression was restricted to the terminals of sensory neurons terminating in lamina llinner. P2X(3) receptors were expressed in approximately e qual numbers of sensory neurons projecting to skin and viscera but in very few of those innervating skeletal muscle. P2X(3) receptors were f ound 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), deliver ed 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 n onpeptidergic nociceptors. P2X(3) receptors are down-regulated followi ng peripheral nerve injury and their expression can be regulated by GD NF.