Mustafa Golam, Hou Jiamei, Tsuda Shigeharu, Nelson Rachel, Sinharoy Ankita, Wilkie Zachary, Pandey Rahul, Caudle Robert M, Neubert John K, Thompson Floyd J, Bose Prodip
Brain Rehabilitation Research Center of Excellence, Malcom Randall VA Medical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL 32608-1197, USA; Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610-0144, USA.
Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610-0144, USA.
Neuropharmacology. 2016 Aug;107:27-39. doi: 10.1016/j.neuropharm.2016.03.016. Epub 2016 Mar 10.
Post-traumatic headache (PTH) following TBI is a common and often persisting pain disability. PTH is often associated with a multimodal central pain sensitization on the skin surface described as allodynia. However, the particular neurobiology underlying cTBI-induced pain disorders are not known. These studies were performed to assess trigeminal sensory sensitization and to determine if sensitization measured behaviorally correlated with detectable changes in portions of the trigeminal sensory system (TSS), particularly trigeminal nucleus, thalamus, and sensory cortex. Thermal stimulation is particularly well suited to evaluate sensitization and was used in these studies. Recent advances in the use of reward/conflict paradigms permit use of operant measures of behavior, versus reflex-driven response behaviors, for thermal sensitization studies. Thus, to quantitate facial thermal sensitization (allodynia) in the setting of acute TBI, the current study utilized an operant orofacial pain reward/conflict testing paradigm to assess facial thermal sensitivity in uninjured control animals compared with those two weeks after cTBI in a rodent model. Significant reductions in facial contact/lick behaviors were observed in the TBI animals using either cool or warm challenge temperatures compared with behaviors in the normal animals. These facial thermal sensitizations correlated with detectable changes in multiple levels of the TSS. The immunohistochemical (IHC) studies revealed significant alterations in the expression of the serotonin (5-HT), neurokinin 1 receptor (NK1R), norepinephrine (NE), and gamma-aminobutyric acid (GABA) in the caudal trigeminal nucleus, thalamic VPL/VPM nucleus, and sensory cortex of the orofacial pain pathways. There was a strong correlation between increased expression of certain IHC markers and increased behavioral markers for facial sensitization. The authors conclude that TBI-induced changes observed in the TSS are consistent with the expression of generalized facial allodynia following cTBI. To our knowledge, this is the first report of orofacial sensitization correlated with changes in selected neuromodulators/neurotransmitters in the TSS following experimental mild TBI.
创伤性脑损伤（TBI）后的创伤后头痛（PTH）是一种常见且常常持续存在的疼痛性残疾。PTH通常与皮肤表面的多模式中枢性疼痛敏化有关，表现为痛觉过敏。然而，cTBI诱发的疼痛障碍背后的具体神经生物学机制尚不清楚。进行这些研究是为了评估三叉神经感觉敏化，并确定行为学测量的敏化是否与三叉神经感觉系统（TSS）部分区域，特别是三叉神经核、丘脑和感觉皮层的可检测变化相关。热刺激特别适合评估敏化，在这些研究中被采用。奖励/冲突范式使用方面的最新进展允许在热敏化研究中使用操作性行为测量，而不是反射驱动的反应行为。因此，为了定量急性TBI情况下的面部热敏化（痛觉过敏），本研究利用操作性口面部疼痛奖励/冲突测试范式，在啮齿动物模型中评估未受伤对照动物与cTBI两周后的动物的面部热敏感性。与正常动物的行为相比，使用冷或热刺激温度时，TBI动物的面部接触/舔舐行为显著减少。这些面部热敏化与TSS多个水平的可检测变化相关。免疫组织化学（IHC）研究显示，在口面部疼痛通路的尾侧三叉神经核、丘脑腹后外侧核/腹后内侧核以及感觉皮层中，血清素（5-HT）、神经激肽1受体（NK1R）、去甲肾上腺素（NE）和γ-氨基丁酸（GABA）的表达有显著改变。某些IHC标记物表达增加与面部敏化行为标记物增加之间存在很强的相关性。作者得出结论，在TSS中观察到的TBI诱发变化与cTBI后全身性面部痛觉过敏的表现一致。据我们所知，这是第一份关于实验性轻度TBI后口面部敏化与TSS中选定神经调质/神经递质变化相关的报告。
