کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6018948 | 1186530 | 2012 | 10 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: P2X3-mediated peripheral sensitization of neuropathic pain in resiniferatoxin-induced neuropathy P2X3-mediated peripheral sensitization of neuropathic pain in resiniferatoxin-induced neuropathy](/preview/png/6018948.png)
Patients suffering from sensory neuropathy due to skin denervation frequently have paradoxical manifestations of reduced nociception and neuropathic pain. However, there is a lack of satisfactory animal models to investigate these phenomena and underlying mechanisms. We developed a mouse system of neuropathy induced by resiniferatoxin (RTX), a capsaicin analog, and examined the functional significance of P2X3 receptor in neuropathic pain. From day 7 of RTX neuropathy, mice displayed mechanical allodynia (p < 0.0001) and thermal hypoalgesia (p < 0.0001). After RTX treatment, dorsal root ganglion (DRG) neurons of the peripherin type were depleted (p = 0.012), while neurofilament (+) DRG neurons were not affected (p = 0.62). In addition, RTX caused a shift in neuronal profiles of DRG: (1) increased in P2X3 receptor (p = 0.0002) and ATF3 (p = 0.0006) but (2) reduced TRPV1 (p = 0.036) and CGRP (p = 0.015). The number of P2X3(+)/ATF3(+) neurons was linearly correlated with mechanical thresholds (p = 0.0017). The peripheral expression of P2X3 receptor in dermal nerves was accordingly increased (p = 0.016), and an intraplantar injection of the P2X3 antagonists, A-317491 and TNP-ATP, relieved mechanical allodynia in a dose-dependent manner. In conclusion, RTX-induced sensory neuropathy with upregulation of P2X3 receptor for peripheral sensitization of mechanical allodynia, which provides a new therapeutic target for neuropathic pain after skin denervation.
⺠We modeled a mouse painful neuropathy induced by resiniferatoxin which depleted TRPV1 neurons. ⺠P2X3 receptor became upregulated in dorsal root ganglia neurons. ⺠The expression of P2X3 receptors was correlated with mechanical thresholds. ⺠P2X3 receptor was responsible for peripheral sensitization of neuropathic pain.
Journal: Experimental Neurology - Volume 235, Issue 1, May 2012, Pages 316-325