Functional up-regulation of P2X3 receptors in dorsal root ganglion in a rat model of bone cancer pain

Background Cancer-induced bone pain remains a clinical challenge due to the poor understanding of the mechanisms. Recent study revealed extracellular adenosine triphosphate (ATP) and P2X receptors may be implicated in nociceptive signalling under cancer pain state. Therefore, here we investigated the potential role of P2X3 receptor in a rat model of bone cancer pain. Methods Walker 256 tumour cells were inoculated into the left tibia of Wistar rats. The model was verified by X-ray imaging, pathology and behaviour examinations. The expression of P2X3 receptors in dorsal root ganglia (DRG) was examined. Functional significance of altered P2X3 receptors was investigated by measuring influx upon a,beta-meATP stimulation in acutely dissociated DRG neurons. Moreover, A-317491, an antagonist of P2X3 receptors, was administrated intrathecally or locally to evaluate its analgesia effect in the cancer pain animals. Results The P2X3 receptor was up-regulated for about 50% in DRG neurons in rats with bone cancer at both protein and mRNA levels and correlated with the pain behaviour in bone cancer rats. A 51.9% increase of a,beta-me ATP (10?mu M, for 4?s) evoked transient response currents and a higher percentage of neurons responsive to the application of a,beta-me ATP was detected in bone cancer rats. Intrathecal or local injection of A-317491 significantly attenuated pain behaviour induced by bone cancer. Conclusions These results suggest that the P2X3 receptor is functionally up-regulated in DRG in cancer rats. P2X3 receptor is a promising target for therapeutic intervention in cancer patients for pain management.