Department of Pharmacology and Physiology and the Henry and Amelia Nasrallah Center for Neuroscience, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.
Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
Trends Pharmacol Sci. 2020 Nov;41(11):851-867. doi: 10.1016/j.tips.2020.09.006. Epub 2020 Oct 1.
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 sphingosine-1-phosphate (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 signaling. Here, we summarize the role of 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.
慢性疼痛是一种改变生活的疾病，影响着数百万人。目前的治疗方法不够充分，长期治疗会带来严重的副作用，特别是对阿片类药物的依赖和成瘾。因此，识别非麻醉性镇痛药至关重要。临床前和临床研究表明，鞘脂代谢改变有助于神经病理性疼痛的发展。临床上用于非疼痛疾病的功能性鞘氨醇-1-磷酸 (S1P) 受体 1 (S1PR1) 拮抗剂，如 FTY720/芬戈莫德，正在成为非麻醉性镇痛药，这支持了将芬戈莫德重新用于慢性疼痛治疗，并为专注于 S1P 信号的药物发现提供了动力。在这里，我们总结了 S1P 在疼痛中的作用，强调了靶向 S1P 轴开发非麻醉性治疗药物的潜力，这反过来有望有助于减少阿片类止痛药的滥用，并解决持续存在的阿片类药物流行问题。
