Traumatic Brain Injury Disrupts Pain Signaling in the Brainstem and Spinal Cord
Traumatic Brain Injury Disrupts Pain Signaling in the Brainstem and Spinal Cord
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DOI：
10.1089/neu.2017.5411
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发表时间：
2018-04-30
影响因子：
4.2
通讯作者：
Clark, J. David
中科院分区：
文献类型：
--
作者：
Irvine, Karen-Amanda;Sahbaie, Peyman;Clark, J. David
慢性疼痛是创伤性脑损伤（TBI）的常见后果，可增加患者的痛苦并对康复工作构成重大挑战。不幸的是，对TBI与疼痛的联系机制知之甚少，并且仍然缺乏针对TBI相关疼痛的特定治疗方法。我们的实验室已经表明，TBI导致疼痛敏感性在远离原发性损伤部位的区域，脊髓基因表达的变化可能是这种敏感性的基础。本研究的目的是探讨从脑干下行的疼痛调节通路在TBI后疼痛中的作用。在一种类型的下行抑制，弥漫性有害抑制控制（DNIC）的缺陷，已被认为是负责慢性疼痛的发展，允许过度和不受控制的传入伤害性输入。在这里，我们从两个方面扩展了我们对TBI后疼痛的认识：（1）通过使用TBI的大鼠侧向流体冲击（LFP）模型概述参与DNIC的脑和脊髓的疼痛相关中心的神经病理学，和（2）通过评估有效的组蛋白乙酰转移酶抑制剂漆树酸（AA）的作用，LFP诱导的疼痛行为和神经病理学的影响。结果表明，TBI可诱导短暂的机械性异常性疼痛和DNIC的慢性持续性丧失。此外，虽然短期AA治疗可以阻断急性伤害性敏化和一些早期神经病理学变化，但这种治疗既不能防止DNIC的丧失，也不能改变脑或脊髓中的长期神经病理学变化。
Chronic pain is a common consequence of traumatic brain injury (TBI) that can increase the suffering of a patient and pose a significant challenge to rehabilitative efforts. Unfortunately, the mechanisms linking TBI to pain are poorly understood, and specific treatments for TBI-related pain are still lacking. Our laboratory has shown that TBI causes pain sensitization in areas distant to the site of primary injury, and that changes in spinal gene expression may underlie this sensitization. The aim of this study was to examine the roles that pain modulatory pathways descending from the brainstem play in pain after TBI. Deficiencies in one type of descending inhibition, diffuse noxious inhibitory control (DNIC), have been suggested to be responsible for the development of chronic pain by allowing excess and uncontrolled afferent nociceptive inputs. Here we expand our knowledge of pain after TBI in two ways: (1) by outlining the neuropathology in pain-related centers of the brain and spinal cord involved in DNIC using the rat lateral fluid percussion (LFP) model of TBI, and (2) by evaluating the effects of a potent histone acetyl transferase inhibitor, anacardic acid (AA), on LFP-induced pain behaviors and neuropathology when administered for several days after TBI. The results revealed that TBI induces transient mechanical allodynia and a chronic persistent loss of DNIC. Further, while short-term AA treatment can block acute nociceptive sensitization and some early neuropathological changes, this treatment neither prevented the loss of DNIC nor did it alter long-term neuropathological changes in the brain or spinal cord.