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18/02/2014;Â 18Ã¢‚Â 57.12 Western o2 671 900 m30ine only) \[[@R28]\]. In addition, the pharmacokinetic profile of glyburide is not altered by concomitant amlodipine (only weakly inhibits the active metabolite of glyburide) \[[@R27]\]. However, one should consider that a relatively large amount of IV administered ATP (2.5 mg/kg) is needed to create local ATP-P2X7 dependent persistent neuroinflammation and spinal cord damage \[[@R36]\]. A second major advantage of oral ATP-P2X7 inhibitors is their excellent safety profile \[[@R26]\]. The risk of hypoglycemia is low due to the risk of excessive insulin secretion and hyperinsulinemia \[[@R26]\]. In diabetes, ATP-P2X7 inhibition could thus offer a therapeutic advantage over current available pharmacological treatments.
In summary, the present data demonstrate that ATP is the major mediator of late mechanical hyperalgesia and neuropathic pain in the rat, which is consistent with the finding that ATP-P2X7 are crucial for the development of neuropathic pain in mice \[[@R30]\]. P2X7-mediated neuroimmune responses are of particular importance since functional P2X7-R were observed on nociceptive DRG cells. In addition, P2X7-R blockade in the spinal cord can be anti-hyperalgesic. Hence, targeting P2X7-R function holds promise for the management of neuropathic pain.
This study was supported by the EJLB Foundation and the European Commission (FP7-MIRP grant 226357 and Marie Curie Actions-Cofund project 321993).
The authors declare that they have
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