Widespread pain sensitization after partial infraorbital nerve transection in MRL/MPJ mice.
Widespread pain sensitization after partial infraorbital nerve transection in MRL/MPJ mice.
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MRL/MPJ 小鼠部分眶下神经横断后广泛的疼痛敏化
DOI：
10.1097/j.pain.0000000000000432
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发表时间：
2016
期刊：
影响因子：
7.4
通讯作者：
Chen Zhong
中科院分区：
文献类型：
--
作者：
Zhang Shi-Hong;Yu Jie;Lou Guo-Dong;Tang Ying-Ying;Wang Ran-Ran;Hou Wei-Wei;Chen Zhong
临床研究表明，慢性疼痛可以扩散到邻近甚至远距离的身体区域，在一些患者。然而，很少有人知道这是如何发生的。在这项研究中，我们发现，部分眶下神经横断（p-IONX）在MRL/MPJ小鼠诱导不仅显着的和持久的口面热痛觉过敏，但热痛觉过敏从术后第3天（PO）和触觉异常性疼痛从第7天PO在双侧后爪。在p-IONX后的早期阶段，后爪的疼痛敏感性与面部热痛觉过敏呈负相关，而不是晚期。在c-Fos快速激活后，腰背角神经元的兴奋性和兴奋性突触传递分别从PO第3天和第7天开始升高。此外，p-IONX后的小胶质细胞活化以时间依赖性的方式从延髓中的Vc向尾侧传递到腰后角。米诺环素在p-IONX后的早期而非晚期抑制小胶质细胞活化可推迟和减弱后爪的疼痛敏感性。这些结果表明，在MRL/MPJ小鼠中p-IONX后的神经性疼痛从口面区域扩散到远处的躯体区域，并且脊髓中中枢致敏的头-尾传递参与疼痛超敏性的扩散过程。
Clinical studies show that chronic pain can spread to adjacent or even distant body regions in some patients. However, little is known about how this happens. In this study, we found that partial infraorbital nerve transection (p-IONX) in MRL/MPJ mice induced not only marked and long-lasting orofacial thermal hyperalgesia but also thermal hyperalgesia from day 3 postoperatively (PO) and tactile allodynia from day 7 PO in bilateral hind paws. Pain sensitization in the hind paw was negatively correlated with facial thermal hyperalgesia at early but not late stage after p-IONX. After a rapid activation of c-Fos, excitability and excitatory synaptic neurotransmission in lumbar dorsal horn neurons were elevated from day 3 and day 7 PO, respectively. In addition, microglial activation after p-IONX transmitted caudally from the Vc in the medulla to lumber dorsal horn in a time-dependent manner. Inhibition of microglial activation by minocycline at early but not late stage after p-IONX postponed and attenuated pain sensitization in the hind paw. These results indicate that neuropathic pain after p-IONX in MRL/MPJ mice spreads from the orofacial region to distant somatic regions and that a rostral–caudal transmission of central sensitization in the spinal cord is involved in the spreading process of pain hypersensitivity.