Bone marrow stromal cells produce long-term pain relief in rat models of persistent pain.
Bone marrow stromal cells produce long-term pain relief in rat models of persistent pain.
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作者：
Guo, Wei;Wang, Hu;Zou, Shiping;Gu, Ming;Watanabe, Mineo;Wei, Feng;Dubner, Ronald;Huang, George T. -J.;Ren, Ke
关键词：
慢性疼痛很难治疗，是主要的健康问题。骨髓基质细胞（BMSCs）作为一种基于细胞的治疗候选者已经引起了相当大的兴趣。骨髓间充质干细胞易于获得，并且易于分离和体外扩增。临床研究表明，直接注射骨髓间充质干细胞不会产生不良的副作用，耐受性好，安全性好。在这里，我们发现单次全身（静脉注射）或局部（病变部位）注射大鼠原代骨髓间充质干细胞可以逆转大鼠损伤后的疼痛超敏反应，并且这种效果持续到研究结束时22周。在BMSC输注后1-5周测试时，疼痛超敏反应被盐酸纳洛酮（一种作用于外周和中枢的阿片受体拮抗剂）重新点燃。相比之下，外周作用的阿片受体拮抗剂纳洛酮（naloxone methiodide）仅在BMSC治疗的前3周重新点燃痛觉过敏。RNA干扰（RNAi）对脑干mu阿片受体的局灶性下调逆转了骨髓间充质干细胞的作用，当RNAi在骨髓间充质干细胞移植后5周而不是1周引入时。因此，骨髓间充质干细胞产生了长期的疼痛缓解，这种效果涉及在不同的时间域激活外周和中枢阿片受体。这些发现促使研究阐明骨髓间质干细胞诱导的疼痛缓解作用的细胞机制，并将这些观察结果转化为临床研究。
Chronic pain conditions are difficult to treat and are major health problems. Bone marrow stromal cells (BMSCs) have generated considerable interest as a candidate for cell-based therapy. BMSCs are readily accessible and are easy to isolate and expand ex vivo. Clinical studies show that direct injection of BMSCs does not produce unwanted side effects and is well tolerated and safe. Here, we show that a single systemic (intravenous) or local injection (into the lesion site) of rat primary BMSCs reversed pain hypersensitivity in rats after injury and that the effect lasted until the conclusion of the study at 22 weeks. The pain hypersensitivity was rekindled by naloxone hydrochloride, an opioid receptor antagonist that acts peripherally and centrally, when tested at 1–5 weeks after BMSC infusion. In contrast, naloxone methiodide, a peripherally acting opioid receptor antagonist, only rekindled hyperalgesia in the first 3 weeks of BMSC treatment. Focal downregulation of brainstem mu opioid receptors by RNA interference (RNAi) reversed the effect of BMSCs, when RNAi was introduced at 5- but not 1-week after BMSC transplantation. Thus, BMSCs produced long-term relief of pain and this effect involved activation of peripheral and central opioid receptors in distinct time domains. The findings prompt studies to elucidate the cellular mechanisms of the BMSC-induced pain relieving effect and translate these observations into clinical settings.
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影响因子：
3.5
作者：
Diatchenko, L;Slade, GD;Maixner, W
通讯作者：
Maixner, W
DOI：
10.1152/ajpheart.00094.2008
发表时间：
2008-08
期刊：
American journal of physiology. Heart and circulatory physiology
影响因子：
--
作者：
Carr CA;Stuckey DJ;Tatton L;Tyler DJ;Hale SJ;Sweeney D;Schneider JE;Martin-Rendon E;Radda GK;Harding SE;Watt SM;Clarke K
通讯作者：
Clarke K
影响因子：
5.3
作者：
Guo, W;Robbins, MT;Ren, K
通讯作者：
Ren, K
影响因子：
7.6
作者：
Huang GT;Gronthos S;Shi S
通讯作者：
Shi S
影响因子：
2.1
作者：
Holzer, U.;van Royen-Kerkhof, A.;Wulffraat, N.
通讯作者：
Wulffraat, N.