TNF signaling contributes to the development of nociceptive sensitization in a tibia fracture model of complex regional pain syndrome type I
TNF signaling contributes to the development of nociceptive sensitization in a tibia fracture model of complex regional pain syndrome type I
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DOI：
10.1016/j.pain.2007.10.013
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发表时间：
2008-07-31
期刊：
影响因子：
7.4
通讯作者：
Kingery, Wade S.
中科院分区：
文献类型：
--
作者：
Sabsovich, Ilya;Guo, Tian-Zhi;Kingery, Wade S.
大鼠胫骨骨折后可引起一系列类似于复杂性局部疼痛综合征I型（CRPS 1）的伤害性、血管性和骨骼性变化。我们推测，促炎细胞因子肿瘤坏死因子α（TNF）可能介导骨折后CRPS样变化的发展。采用RT-PCR和EIA法检测骨折后皮肤、神经和骨组织中TNF表达和含量的变化。双侧后爪厚度，温度和伤害性阈值进行了测定，骨微结构进行了测量，使用微型计算机断层扫描。腰髓Fos免疫染色用于定量Fos阳性神经元。基线测试后，胫骨远端骨折，后膝关节铸造4周。在28天内每3天向大鼠皮下注射可溶性I型TNF受体（sTNF-R1，5 mg/kg/d）或盐水，然后在骨折后4周重新测试。胫骨骨折慢性上调后爪皮肤和坐骨神经的TNF表达和蛋白水平。骨折后，大鼠出现后爪机械异常性疼痛和失重，sTNF-R1治疗可逆转。与行为学数据一致，骨折后脊髓Fos增加，这种作用被sTNF-R1治疗抑制。总的来说，这些数据表明，促进TNF信号在后肢是一个重要的调解人的慢性区域伤害性致敏骨折后，但并没有促成后肢温暖，水肿，和骨丢失中观察到的CRPS I模型。由Elsevier B. V.代表国际疼痛研究协会出版。
Tibia fracture in rats initiates a cascade of nociceptive, vascular, and bone changes resembling complex regional pain syndrome type I (CRPS 1), Previous studies suggest that the pathogenesis of these changes is attributable to an exaggerated regional inflammatory response to injury. We postulated that the pro-inflammatory cytokine tumor necrosis factor alpha (TNF) might mediate the development of CRPS-like changes after fracture. RT-PCR and EIA assays were used to evaluate changes in TNF expression and content in skin, nerve, and bone after fracture. Bilateral hindpaw thickness, temperature, and nociceptive thresholds were determined, and bone microarchitecture was measured using microcomputed tomography. Lumbar spinal cord Fos immunostaining was performed for quantification of Fos positive neurons. After baseline testing, the distal tibia was fractured and the hindhillb casted for 4 weeks. The rats were subcutaneously injected either with a soluble TNF receptor type I (sTNF-R1, 5 mg/kg/d) or saline every 3 days over 28 days and then were retested at 4 weeks post-fracture. Tibia fracture chronically upregulated TNF expression and protein levels in the hindpaw skin and sciatic nerve. After fracture the rats developed hindpaw mechanical allodynia and unweighting, which were reversed by sTNF-R1 treatment. Consistent with the behavioral data, spinal Fos increased after fracture and this effect was inhibited by sTNF-R1 treatment. Collectively, these data suggest that facilitated TNF signaling in the hindlimb is an important mediator of chronic regional nociceptive sensitization after fracture, but does not contribute to the hindlimb warmth, edema, and bone loss observed in this CRPS I model. Published by Elsevier B.V. on behalf of International Association for the Study of Pain.