Targeting the Sphingosine-1-Phosphate Axis for Developing Non-narcotic Pain Therapeutics.
Targeting the Sphingosine-1-Phosphate Axis for Developing Non-narcotic Pain Therapeutics.
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DOI：
10.1016/j.tips.2020.09.006
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发表时间：
2020-11
影响因子：
13.8
通讯作者：
Salvemini D
中科院分区：
文献类型：
--
作者：
Squillace S;Spiegel S;Salvemini D
慢性疼痛是一种影响数百万人的生活的疾病。目前的治疗方法不足，长期治疗会带来严重的副作用，尤其是对阿片类药物的依赖和成瘾。识别非麻醉性镇痛药至关重要。临床前和临床研究表明，鞘脂代谢的改变导致神经性疼痛的发生。功能性 S1P 受体 1 (S1PR1) 拮抗剂，例如 FTY720/芬戈莫德，在临床上用于非疼痛病症，正在作为非麻醉性镇痛药出现，支持芬戈莫德重新用于慢性疼痛治疗，并促进专注于 S1P 信号传导的药物发现。在这里，我们总结了 1-磷酸鞘氨醇 (S1P) 在疼痛中的作用，以强调针对 S1P 轴开发非麻醉疗法的潜力，这反过来有望有助于减少阿片类止痛药物的滥用并解决持续存在的阿片类药物流行问题。
Chronic pain is a life-altering condition affecting millions of people. Current treatments are inadequate and prolonged therapies come with severe side effects, especially dependence and addiction to opiates. Identification of non-narcotic analgesics is of paramount importance. Preclinical and clinical studies suggest that sphingolipid metabolism alterations contribute to neuropathic pain development. Functional S1P receptor 1 (S1PR1) antagonists, such as FTY720/Fingolimod, used clinically for non-pain conditions, are emerging as non-narcotic analgesics, supporting the repurposing of Fingolimod for chronic pain treatment and energizing drug discovery focused on S1P signalling. Here we summarize the role of sphingosine-1-phosphate (S1P) in pain to highlight the potential of targeting the S1P axis towards development of non-narcotic therapeutics which in turn will hopefully help lessen misuse of opioid pain medications and address the ongoing opioid epidemic.
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