Hirsch Silke, Ibrahim Alaa, Krämer Laura, Escolano-Lozano Fabiola, Schlereth Tanja, Birklein Frank
Department of Neurology, University of Mainz, Mainz, Germany.
Department of Neurology, University of Mainz, Mainz, Germany.
J Pain. 2017 Apr;18(4):468-476. doi: 10.1016/j.jpain.2016.12.010. Epub 2017 Jan 3.
Bone fracture with subsequent immobilization of the injured limb can cause complex regional pain syndrome (CRPS) in humans. Mechanisms of CRPS are still not completely understood but bone fracture with casting in mice leads to a similar post-traumatic inflammation as seen in humans and might therefore be an analog to human CRPS. In this article we report behavioral and spinal electrophysiological changes in mice that developed swelling of the paw, warming of the skin, and pain in the injured limb after bone fracture. The receptive field sizes of spinal neurons representing areas of the hind paws increased after trauma and recovered over time-as did the behavioral signs of inflammation and pain. Interestingly, both sides-the ipsi- and the contralateral limb-showed changes in mechanical sensitivity and neuronal network organization after the trauma. The characteristics of evoked neuronal responses recorded in the dorsal horn of the mice were similar between uninjured controls and fractured animals. However, we saw a caudal extension of the represented area of the hind paw in the spinal cord at the injured side and an occurrence of large receptive fields of wide dynamic range neurons. The findings in mice compare with human symptoms in CRPS with ipsi- and also contralateral allodynia and pain. In all mice tested, all signs subsided 12 weeks after trauma. Our data suggest a significant reorganization of spinal circuitry after limb trauma, in a degree more comprehensive than most models of neuropathies. This process seems to be reversible in the rodent.
The discovery of enlarged spinal neuronal receptive fields and caudal extension of the representation area of the injured body part, which subsides several weeks after a bone trauma in mice, might give hope to patients of CRPS if-in the future-we are able to translate the rodent recovery mechanisms to post-traumatic humans.
人类肢体骨折并随后固定受伤肢体可导致复杂性区域疼痛综合征（CRPS）。CRPS的机制仍未完全明确，但小鼠骨折打石膏后会引发与人类相似的创伤后炎症，因此可能是人类CRPS的类似情况。在本文中，我们报告了小鼠在骨折后出现爪部肿胀、皮肤发热和受伤肢体疼痛时的行为及脊髓电生理变化。代表后爪区域的脊髓神经元感受野大小在创伤后增加，并随时间恢复，炎症和疼痛的行为迹象也是如此。有趣的是，创伤后同侧和对侧肢体的机械敏感性和神经网络组织均出现了变化。在未受伤对照组和骨折动物中，小鼠背角记录的诱发神经元反应特征相似。然而，我们发现受伤侧脊髓中后爪代表区域向尾端延伸，且出现了广动力范围神经元的大感受野。小鼠的这些发现与人类CRPS中同侧及对侧痛觉过敏和疼痛的症状相符。在所有测试的小鼠中，所有症状在创伤后12周消退。我们的数据表明，肢体创伤后脊髓回路发生了显著重组，其程度比大多数神经病变模型更为全面。在啮齿动物中，这个过程似乎是可逆的。
在小鼠骨折创伤数周后，受伤身体部位的脊髓神经元感受野扩大及代表区域向尾端延伸的现象被发现。如果未来我们能够将啮齿动物的恢复机制应用于创伤后的人类，这可能会给CRPS患者带来希望。
