Herpes simplex virus vector-mediated expression of interleukin-10 reduces below-level central neuropathic pain after spinal cord injury.
Herpes simplex virus vector-mediated expression of interleukin-10 reduces below-level central neuropathic pain after spinal cord injury.
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单纯疱疹病毒介导的白细胞介素-10的表达减少了脊髓损伤后的中枢性神经性疼痛。
DOI：
10.1177/1545968312445637
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发表时间：
2012-09
影响因子：
4.2
通讯作者：
Fink DJ
中科院分区：
文献类型：
--
作者：
Lau D;Harte SE;Morrow TJ;Wang S;Mata M;Fink DJ
脊髓背角的神经免疫激活在周围神经损伤后慢性疼痛的发病机制中起重要作用。我们想研究神经免疫激活在创伤性脊髓损伤（SCI）后神经病理性疼痛中的作用。在雄性Sprague道利大鼠中通过T12椎板切除术的受控钝性撞击来创建右侧SCI。疼痛相关的行为进行了评估，使用诱发反射反应和操作性冲突回避测试。神经免疫激活被抗炎细胞因子白细胞介素-10（IL-10）阻断，IL-10由基于非复制型单纯疱疹病毒（HSV）的基因转移载体（vIL-10）递送。采用免疫组化和Western blot评估神经免疫激活标志物。脊髓损伤后一周，受伤的动物表现出机械异常性疼痛，热痛觉过敏，和机械痛觉过敏的后肢低于损伤水平。与受伤大鼠或接种对照载体的受伤大鼠相比，接种vIL 10的动物在所有这些测量中具有统计学显著性降低。与注射对照载体的损伤大鼠相比，注射vIL 10的损伤大鼠的回避行为与显著减少的疼痛一致。这些行为学结果与脊髓肿瘤坏死因子α（mTNFα）表达（通过Western blot评估）和星形胶质细胞活化（通过胶质细胞酸性蛋白免疫组织化学评估）的显著降低相关。脊髓损伤后低水平疼痛的特征是神经免疫激活（mTNFα和星形胶质细胞激活增加）。通过HSV介导的IL-10递送的神经免疫应答的钝化减少了疼痛相关的行为，并且可能代表潜在的新型治疗剂。
Neuroimmune activation in the spinal dorsal horn plays an important role in the pathogenesis of chronic pain after peripheral nerve injury. We wanted to examine the role of neuroimmune activation in below level neuropathic pain after traumatic spinal cord injury (SCI). Right hemilateral SCI was created in male Sprague Dawley rats by controlled blunt impact through a T12 laminectomy. Pain related behaviors were assessed using both evoked reflex responses and an operant conflict-avoidance test. Neuroimmune activation was blocked by the anti-inflammatory cytokine interleukin-10 (IL-10) delivered by a non-replicating herpes simplex virus (HSV)-based gene transfer vector (vIL10). Markers of neuroimmune activation were assessed using immunohistochemistry and Western blot. One week after SCI, injured animals demonstrated mechanical allodynia, thermal hyperalgesia, and mechanical hyperalgesia in the hind limbs below the level of injury. Animals inoculated with vIL10 had a statistically significant reduction in all of these measures compared to injured rats or injured rats inoculated with control vector. Conflict-avoidance behavior of injured rats inoculated with vIL10 was consistent with significantly reduced pain compared to injured rats injected with control vector. These behavioral results correlated with a significant decrease in spinal tumor necrosis factor α (mTNFα) expression assessed by Western blot and astrocyte activation assessed by glial fibrillary acidic protein immunohistochemistry. Below level pain after SCI is characterized by neuroimmune activation (increase mTNFα and astrocyte activation). Blunting of the neuroimmune response by HSV-mediated delivery of IL-10 reduced pain-related behaviors, and may represent a potential novel therapeutic agent.
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影响因子：
3.4
作者：
Ledeboer, A;Brevé, JJP;Van Dam, AM
通讯作者：
Van Dam, AM
影响因子：
3.3
作者：
Gwak, Y. S.;Hulsebosch, C. E.
通讯作者：
Hulsebosch, C. E.
影响因子：
7.4
作者：
Baastrup, Cathrine;Maersk-Moller, Camilla Charlotte;Finnerup, Nanna Brix
通讯作者：
Finnerup, Nanna Brix
影响因子：
4.2
作者：
Christensen, MD;Hulsebosch, CE
通讯作者：
Hulsebosch, CE
影响因子：
7.4
作者：
Ledeboer, A;Sloane, EM;Watkins, LR
通讯作者：
Watkins, LR