Lyons D N, Kniffin T C, Zhang L P, Danaher R J, Miller C S, Bocanegra J L, Carlson C R, Westlund K N
Department of Physiology, University of Kentucky, United States.
Department of Psychology, University of Kentucky, United States.
Neuroscience. 2015 Jun 4;295:126-38. doi: 10.1016/j.neuroscience.2015.03.051. Epub 2015 Mar 27.
Our laboratory previously developed a novel neuropathic and inflammatory facial pain model for mice referred to as the Trigeminal Inflammatory Compression (TIC) model. Rather than inducing whole nerve ischemia and neuronal loss, this injury induces only slight peripheral nerve demyelination triggering long-term mechanical allodynia and cold hypersensitivity on the ipsilateral whisker pad. The aim of the present study is to further characterize the phenotype of the TIC injury model using specific behavioral assays (i.e. light-dark box, open field exploratory activity, and elevated plus maze) to explore pain- and anxiety-like behaviors associated with this model. Our findings determined that the TIC injury produces hypersensitivity 100% of the time after surgery that persists at least 21 weeks post injury (until the animals are euthanized). Three receptive field sensitivity pattern variations in mice with TIC injury are specified. Animals with TIC injury begin displaying anxiety-like behavior in the light-dark box preference and open field exploratory tests at week eight post injury as compared to sham and naïve animals. Panic anxiety-like behavior was shown in the elevated plus maze in mice with TIC injury if the test was preceded with acoustic startle. Thus, in addition to mechanical and cold hypersensitivity, the present study identified significant anxiety-like behaviors in mice with TIC injury resembling the clinical symptomatology and psychosocial impairments of patients with chronic facial pain. Overall, the TIC injury model's chronicity, reproducibility, and reliability in producing pain- and anxiety-like behaviors demonstrate its usefulness as a chronic neuropathic facial pain model.
我们实验室之前为小鼠开发了一种新型的神经性和炎症性面部疼痛模型,称为三叉神经炎性压迫(TIC)模型。该损伤并非诱导全神经缺血和神经元丢失,而是仅诱导轻微的外周神经脱髓鞘,从而引发同侧触须垫的长期机械性异常性疼痛和冷超敏反应。本研究的目的是使用特定的行为学检测方法(即明暗箱、旷场探索活动和高架十字迷宫)进一步表征TIC损伤模型的表型,以探索与该模型相关的疼痛样和焦虑样行为。我们的研究结果表明,TIC损伤在手术后100%会产生超敏反应,且这种反应在损伤后至少持续21周(直至动物被安乐死)。明确了TIC损伤小鼠的三种感受野敏感性模式变化。与假手术组和正常组动物相比,TIC损伤动物在损伤后第8周的明暗箱偏好试验和旷场探索试验中开始表现出焦虑样行为。如果在高架十字迷宫试验前进行听觉惊吓刺激,TIC损伤小鼠会表现出惊恐焦虑样行为。因此,除了机械性和冷超敏反应外,本研究还发现TIC损伤小鼠存在显著的焦虑样行为,类似于慢性面部疼痛患者的临床症状和心理社会障碍。总体而言,TIC损伤模型在产生疼痛样和焦虑样行为方面的慢性、可重复性和可靠性证明了其作为慢性神经性面部疼痛模型的实用性。