P2X3 receptor in injured human sensory neurons

The ATP-gated cation channel P2X(3) is expressed selectively by rat sensory neurones, and may play a role in nociception by binding ATP released from damaged or inflamed tissues. However, the distribution of this channel in human sensory neurons is not known. Using a specific antibody, we have demonstrated intense P2X(3) immunoreactivity within a subset (60%) of small/medium diameter sensory neurones and fine nerve fibres in intact post-mortem human dorsal root ganglia (DRG). Co-localization studies showed <15% overlap with the trkA immunostaining in DRG, indicating that P2X(3) was expressed predominantly in sensory neurons that are also isolectin B4 positive. There was a significant decrease in numbers of P2X(3)-like immunoreactive neurons in human DRG after central axotomy (to 36%), similar to the decrease in rat DRG after peripheral axotomy. However, Western blotting demonstrated a specific 66 kDa band in human DRG and peripheral organs, including intestine, where histochemistry showed P2X(3) immunoreactivity in myenteric plexus neurons. Thus P2X(3) antagonists may be analgesic, but are unlikely to have a selective effect on pain in humans. NeuroReport 11:993-996 (C) 2000 Lippincott Williams & Wilkins.