J X Wu1, M Y Xu, X R Miao, Z J Lu, X M Yuan, X Q Li, W F Yu. 1. Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
Abstract
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 P2X(3) 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 P2X(3) receptors in dorsal root ganglia (DRG) was examined. Functional significance of altered P2X(3) receptors was investigated by measuring influx upon α,β-meATP stimulation in acutely dissociated DRG neurons. Moreover, A-317491, an antagonist of P2X(3) receptors, was administrated intrathecally or locally to evaluate its analgesia effect in the cancer pain animals. RESULTS: The P2X(3) 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 α,β-me ATP (10 μM, for 4 s) evoked transient response currents and a higher percentage of neurons responsive to the application of α,β-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 P2X(3) receptor is functionally up-regulated in DRG in cancer rats. P2X(3) receptor is a promising target for therapeutic intervention in cancer patients for pain management.
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 P2X(3) 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 P2X(3) receptors in dorsal root ganglia (DRG) was examined. Functional significance of altered P2X(3) receptors was investigated by measuring influx upon α,β-meATP stimulation in acutely dissociated DRG neurons. Moreover, A-317491, an antagonist of P2X(3) receptors, was administrated intrathecally or locally to evaluate its analgesia effect in the cancer pain animals. RESULTS: The P2X(3) 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 cancerrats. A 51.9% increase of α,β-me ATP (10 μM, for 4 s) evoked transient response currents and a higher percentage of neurons responsive to the application of α,β-me ATP was detected in bone cancerrats. Intrathecal or local injection of A-317491 significantly attenuated pain behaviour induced by bone cancer. CONCLUSIONS: These results suggest that the P2X(3) receptor is functionally up-regulated in DRG in cancerrats. P2X(3) receptor is a promising target for therapeutic intervention in cancerpatients for pain management.