Departments of Pain Management and Neurosciences, Lerner Research Institute and Anaesthesiology Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
Department of Anesthesiology, Beijing Hospital, No. 1 Dahua Road, Beijing 100730, China.
Sci Rep. 2016 Aug 24;6:32096. doi: 10.1038/srep32096.
More than 240 million opioid prescriptions are dispensed annually to treat pain in the US. The use of opioids is commonly associated with opioid tolerance (OT) and opioid-induced hyperalgesia (OIH), which limit efficacy and compromise safety. The dearth of effective way to prevent or treat OT and OIH is a major medical challenge. We hypothesized that mesenchymal stem cells (MSCs) attenuate OT and OIH in rats and mice based on the understanding that MSCs possess remarkable anti-inflammatory properties and that both OT and chronic pain are associated with neuroinflammation in the spinal cord. We found that the development of OT and OIH was effectively prevented by either intravenous or intrathecal MSC transplantation (MSC-TP), which was performed before morphine treatment. Remarkably, established OT and OIH were significantly reversed by either intravenous or intrathecal MSCs when cells were transplanted after repeated morphine injections. The animals did not show any abnormality in vital organs or functions. Immunohistochemistry revealed that the treatments significantly reduced activation level of microglia and astrocytes in the spinal cord. We have thus demonstrated that MSC-TP promises to be a potentially safe and effective way to prevent and reverse two of the major problems of opioid therapy.
每年有超过 2.4 亿份阿片类药物处方用于治疗美国的疼痛。阿片类药物的使用通常与阿片类药物耐受（OT）和阿片类药物引起的痛觉过敏（OIH）有关，这限制了疗效并危及安全性。缺乏有效预防或治疗 OT 和 OIH 的方法是一个主要的医学挑战。我们假设间充质干细胞（MSCs）可以减轻大鼠和小鼠的 OT 和 OIH，这是基于以下认识：MSCs 具有显著的抗炎特性，而 OT 和慢性疼痛都与脊髓中的神经炎症有关。我们发现，通过静脉内或鞘内 MSC 移植（MSC-TP）在吗啡治疗前进行，可以有效预防 OT 和 OIH 的发展。值得注意的是，当在反复吗啡注射后移植细胞时，静脉内或鞘内 MSCs 可以显著逆转已建立的 OT 和 OIH。动物的重要器官或功能没有任何异常。免疫组织化学显示，这些治疗方法显著降低了脊髓中小胶质细胞和星形胶质细胞的激活水平。因此，我们已经证明，MSC-TP 有望成为预防和逆转阿片类药物治疗的两个主要问题的一种潜在安全有效的方法。
