Neuroinflammation of the spinal cord and nerve roots in chronic radicular pain patients.
Neuroinflammation of the spinal cord and nerve roots in chronic radicular pain patients.
复制标题
DOI：
10.1097/j.pain.0000000000001171
复制
发表时间：
2018-05
期刊：
影响因子：
7.4
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Albrecht DS;Ahmed SU;Kettner NW;Borra RJH;Cohen-Adad J;Deng H;Houle TT;Opalacz A;Roth SA;Melo MFV;Chen L;Mao J;Hooker JM;Loggia ML;Zhang Y
大量临床前研究支持脊髓神经免疫激活在慢性疼痛发病机制中的作用，并且在实验动物中，针对胶质细胞（如小胶质细胞/星形胶质细胞）或巨噬细胞介导的神经炎症反应有效地防止或逆转持续伤害行为的建立。然而，到目前为止，由于缺乏支持神经炎症在人类疼痛中的作用的数据，这些发现转化为临床使用的新疗法受到了阻碍。在这里，我们表明，与健康志愿者相比，患有常见慢性疼痛疾病（腰椎神经根病）的患者在神经孔（包含背根神经节和神经根）和脊髓中表现出神经炎症标志物18kDa转运蛋白（TSPO）水平升高。这些升高显示了一种与患者临床表现相关的空间特异性模式，因为它们在有症状的腿的同侧神经孔（与同一患者的对侧神经孔以及健康对照相比）和大多数尾侧脊髓节段中被观察到，这些脊髓节段已知处理来自这些患者受影响的腰骶神经根的感觉信息（与更多的上节段相比）。此外，神经间孔TSPO信号与透视引导下硬膜外类固醇注射的反应有关，支持其作为神经炎症成像标志物的作用，并强调了这些观察结果的临床意义。这些结果表明，神经系统多个层面的免疫激活是人类神经根性疼痛的潜在重要和临床相关机制，并提示针对免疫细胞激活的治疗可能对慢性疼痛患者有益。
Numerous preclinical studies support the role of spinal neuroimmune activation in the pathogenesis of chronic pain, and targeting glia (e.g., microglia/astrocyte)- or macrophage-mediated neuroinflammatory responses effectively prevents or reverses the establishment of persistent nocifensive behaviors in laboratory animals. However, thus far the translation of those findings into novel treatments for clinical use has been hindered by the scarcity of data supporting the role of neuroinflammation in human pain. Here, we show that patients suffering from a common chronic pain disorder (lumbar radiculopathy), compared to healthy volunteers, exhibit elevated levels of the neuroinflammation marker 18kDa translocator protein (TSPO), in both the neuroforamina (containing dorsal root ganglion and nerve roots) and spinal cord. These elevations demonstrated a pattern of spatial specificity correlating with the patients’ clinical presentation, as they were observed in the neuroforamen ipsilateral to the symptomatic leg (compared to both contralateral neuroforamen in the same patients as well as to healthy controls) and in the most caudal spinal cord segments, which are known to process sensory information from the lumbosacral nerve roots affected in these patients (compared to more superior segments). Furthermore, the neuroforaminal TSPO signal was associated with responses to fluoroscopy-guided epidural steroid injections, supporting its role as an imaging marker of neuroinflammation, and highlighting the clinical significance of these observations. These results implicate immunoactivation at multiple levels of the nervous system as a potentially important and clinically relevant mechanism in human radicular pain, and suggest that therapies targeting immune cell activation may be beneficial for chronic pain patients.
登录
查看更多内容
影响因子：
11.2
作者：
Herranz, Elena;Gianni, Costanza;Louapre, Celine;Treaba, Constantina A.;Govindarajan, Sindhuja T.;Ouellette, Russell;Loggia, Marco L.;Sloane, Jacob A.;Madigan, Nancy;Izquierdo-Garcia, David;Ward, Noreen;Mangeat, Gabriel;Granberg, Tobias;Klawiter, Eric C.;Catana, Ciprian;Hooker, Jacob M.;Taylor, Norman;Ionete, Carolina;Kinkel, Revere P.;Mainero, Caterina
通讯作者：
Mainero, Caterina
影响因子：
7.4
作者：
Liu, Xiaoming;Liu, Hongjun;Jin, Yi
通讯作者：
Jin, Yi
影响因子：
5.7
作者：
Imaizumi, Masao;Briard, Emmanuelle;Fujita, Masahiro
通讯作者：
Fujita, Masahiro
影响因子：
7.6
作者：
Brody, Arthur L.;Hubert, Robert;Mandelkern, Mark A.
通讯作者：
Mandelkern, Mark A.
影响因子：
2.5
作者：
LeBlanc, Brian W.;Zerah, Michele L.;Saab, Carl Y.
通讯作者：
Saab, Carl Y.