Neuropeptide deficient mice have attenuated nociceptive, vascular, and inflammatory changes in a tibia fracture model of complex regional pain syndrome.
Neuropeptide deficient mice have attenuated nociceptive, vascular, and inflammatory changes in a tibia fracture model of complex regional pain syndrome.
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DOI：
10.1186/1744-8069-8-85
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发表时间：
2012-11-28
期刊：
影响因子：
3.3
通讯作者：
Kingery WS
中科院分区：
文献类型：
--
作者：
Guo TZ;Wei T;Shi X;Li WW;Hou S;Wang L;Tsujikawa K;Rice KC;Cheng K;Clark DJ;Kingery WS
四肢远端骨折可引起复杂的局部疼痛综合征（CRPS），包括疼痛、发热、水肿和皮肤炎症。在本研究中，P物质（SP，Tac 1-/-）和CGRP受体（RAMP 1-/-）缺陷小鼠被用于研究神经肽信号传导对胫骨骨折小鼠模型中CRPS样变化的贡献。野生型、Tac 1 −/−和RAMP 1 −/−小鼠经历胫骨骨折和石膏固定3周，然后取出石膏固定，并随时间推移测试后爪机械性异常性疼痛、失重、发热和水肿。在骨折后3周收集后爪皮肤用于免疫测定，并收集股骨用于微CT分析。野生型小鼠在骨折后3周出现后爪异常性疼痛、失重、发热和水肿，但在Tac 1 −/−骨折小鼠中，异常性疼痛和失重减弱，没有发热和水肿。RAMP 1 −/−骨折小鼠具有类似的表现，除了后爪水肿没有减少。在骨折后3周，野生型骨折小鼠的后爪皮肤TNFα、IL-1β、IL-6和NGF水平上调，但在Tac 1 −/−和RAMP 1 −/−骨折小鼠中，仅IL-6水平升高。表皮角质形成细胞是这些炎症介质的细胞来源。IL-6受体拮抗剂部分逆转野生型小鼠骨折后疼痛行为。总之，SP和CGRP是关键的神经肽介质的疼痛行为，血管异常，和上调先天免疫反应观察骨折后肢。我们推测，在Tac 1 −/−和RAMP 1 −/−骨折小鼠中观察到的残余疼痛行为可归因于骨折后在后爪皮肤中观察到的IL-6水平增加。
Distal limb fracture in man can induce a complex regional pain syndrome (CRPS) with pain, warmth, edema, and cutaneous inflammation. In the present study substance P (SP, Tac1−/−) and CGRP receptor (RAMP1−/−) deficient mice were used to investigate the contribution of neuropeptide signaling to CRPS-like changes in a tibia fracture mouse model. Wildtype, Tac1−/−, and RAMP1−/− mice underwent tibia fracture and casting for 3 weeks, then the cast was removed and hindpaw mechanical allodynia, unweighting, warmth, and edema were tested over time. Hindpaw skin was collected at 3 weeks post-fracture for immunoassay and femurs were collected for micro-CT analysis. Wildtype mice developed hindpaw allodynia, unweighting, warmth, and edema at 3 weeks post-fracture, but in the Tac1−/− fracture mice allodynia and unweighting were attenuated and there was no warmth and edema. RAMP1−/− fracture mice had a similar presentation, except there was no reduction in hindpaw edema. Hindpaw skin TNFα, IL-1β, IL-6 and NGF levels were up-regulated in wildtype fracture mice at 3 weeks post-fracture, but in the Tac1−/− and RAMP1−/− fracture mice only IL-6 was increased. The epidermal keratinocytes were the cellular source for these inflammatory mediators. An IL-6 receptor antagonist partially reversed post-fracture pain behaviors in wildtype mice. In conclusion, both SP and CGRP are critical neuropeptide mediators for the pain behaviors, vascular abnormalities, and up-regulated innate immune responses observed in the fracture hindlimb. We postulate that the residual pain behaviors observed in the Tac1−/− and RAMP1−/− fracture mice are attributable to the increased IL-6 levels observed in the hindpaw skin after fracture.
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影响因子：
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作者：
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通讯作者：
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