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Low GRK2 Underlies Hyperalgesic Priming by Glial Cell-Derived Neurotrophic Factor 期刊论文

编号：

5326fda8-88d9-4f68-b4f4-bd918ed757fe
作者：

Wang, HuiJing(汪慧菁)#*^[1,2]Gu, HanXin^[1]Eijkelkamp, Niels^[2];Heijnen, Cobi J.^[3];Kavelaars, Annemieke^[3];
语种：

英文
期刊：

FRONTIERS IN PHARMACOLOGY ISSN：1663-9812 2018 年 9 卷 ; JUN 5
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关键词：

GDNF hyperalgesic priming GRK2 Epac HSV vector ESI-09
摘要：

Background: We recently identified the balance between the level of G protein coupled receptor kinase 2 (GRK2) and Epac1 in nociceptors as a key factor in the transition from acute to chronic pain that occurs in mice 'primed' by an inflammatory stimulus. Here, we examined the contribution of GRK2 and Epac-signaling to growth factor-induced hyperalgesic priming.
Methods: Mice were primed by intraplantar injection with glial cell-derived neurotrophic factor (GDNF). Mechanical allodynia in response to PGE(2) was followed over time in primed and non-primed animals. GRK2 protein levels in dorsal root ganglion (DRG) neurons were quantified by immunohistochemistry. The effect of herpes simplex virus (HSV)-GRK2 amplicons to restore GRK2 levels or of an Epac inhibitor on PGE(2) allodynia in primed mice was examined.
Results: Glial cell-derived neurotrophic factor-induced hyperalgesia disappeared within 12 days. The hyperalgesic response to a subsequent intraplantar injection of PGE(2) was prolonged from <24 h in control mice to more than 72 h in GDNF-primed mice. In male and female primed mice, PGE(2) hyperalgesia was inhibited by oral administration of the Epac inhibitor ESI-09, while the drug had no effect in control mice. Mice primed with GDNF had reduced levels of GRK2 in IB4(+) small DRG neurons, but normal GRK2 levels in IB4(-) DRG neurons. Intraplantar administration of HSV-GRK2 amplicons to increase GRK2 protein levels prevented the prolongation of PGE(2)-induced hyperalgesia in GDNF-primed mice.
Conclusion: Low GRK2 in nociceptors is critical to develop a primed state in response to GDNF and leads to engagement of Epac signaling and transition to chronic PGE(2)-induced hyperalgesia. Increasing GRK2 protein or inhibiting Epac signaling may represent new avenues for preventing transition to a chronic pain state.
推荐引用方式
GB/T 7714：

Wang Hui-Jing,Gu Han-Xin,Eijkelkamp Niels, et al. Low GRK2 Underlies Hyperalgesic Priming by Glial Cell-Derived Neurotrophic Factor [J].FRONTIERS IN PHARMACOLOGY,2018,9.
APA：

Wang Hui-Jing,Gu Han-Xin,Eijkelkamp Niels,Heijnen Cobi J.,&Kavelaars Annemieke.(2018).Low GRK2 Underlies Hyperalgesic Priming by Glial Cell-Derived Neurotrophic Factor .FRONTIERS IN PHARMACOLOGY,9.
MLA：

Wang Hui-Jing, et al. "Low GRK2 Underlies Hyperalgesic Priming by Glial Cell-Derived Neurotrophic Factor" .FRONTIERS IN PHARMACOLOGY 9(2018).
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