类阿片
Wnt信号通路
(+)-纳洛酮
医学
痛觉过敏
阿片受体
火种
背根神经节
神经化学
吗啡
慢性疼痛
炎症
μ-阿片受体
受体
药理学
神经科学
脊髓
信号转导
伤害
内分泌学
内科学
刺激
心理学
生物
细胞生物学
精神科
作者
Mingzheng Wu,Zehua Li,Lei Liang,Pingchuan Ma,Dong Cui,Peng Chen,Genhao Wu,Xue‐Jun Song
出处
期刊:Pain
[Ovid Technologies (Wolters Kluwer)]
日期:2019-11-05
卷期号:161 (3): 532-544
被引量:17
标识
DOI:10.1097/j.pain.0000000000001738
摘要
Abstract Preventing and treating opioid dependence and withdrawal is a major clinical challenge, and the underlying mechanisms of opioid dependence and withdrawal remain elusive. We hypothesized that prolonged morphine exposure or chronic inflammation-induced μ-opioid receptor activity serves as a severe stress that elicits neuronal alterations and recapitulates events during development. Here, we report that Wnt signaling, which is important in developmental processes of the nervous system, plays a critical role in withdrawal symptoms from opioid receptor activation in mice. Repeated exposures of morphine or peripheral inflammation produced by intraplantar injection of complete Freund's adjuvant significantly increase the expression of Wnt5b in the primary sensory neurons in dorsal root ganglion (DRG). Accumulated Wnt5b in DRG neurons quickly transmits to the spinal cord dorsal horn (DH) after naloxone treatment. In the DH, Wnt5b, acts through the atypical Wnt-Ryk receptor and alternative Wnt-YAP/TAZ signaling pathways, contributing to the naloxone-precipitated opioid withdrawal-like behavioral symptoms and hyperalgesia. Inhibition of Wnt synthesis and blockage of Wnt signaling pathways greatly suppress the behavioral and neurochemical alterations after naloxone-precipitated withdrawal. These findings reveal a critical mechanism underlying naloxone-precipitated opioid withdrawal, suggesting that targeting Wnt5b synthesis in DRG neurons and Wnt signaling in DH may be an effective approach for prevention and treatment of opioid withdrawal syndromes, as well as the transition from acute to chronic pain.
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