Institute of Clinical Pharmacology, Goethe-University Hospital, 60590 Frankfurt, Germany.
Pain. 2019 Jun;160(6):1431-1447. doi: 10.1097/j.pain.0000000000001518.
Inflammation or injuries of the trigeminal nerve are often associated with persistent facial pain and its sequelae. A number of models have been described to study trigeminal pain in rodents, but the long-lasting behavioral consequences are unknown. This study characterizes the impact of a distal infraorbital nerve injury, called DIONI, which consists of ligature and transection of distal fibers of the infraorbital nerve. We assessed nociception using a conflict paradigm and optogenetics, and a set of reward, aversion, spatial, temporal, and competition tasks in the IntelliCage to study multiple aspects of cognition, circadian rhythms, and social interactions in groups of mice in home cage environments. Mice with DIONI developed cold and mechanical allodynia, and hypersensitivity towards blue light stimulation. They maintained a long-lasting memory of aversive stimuli (airpuff from above), but had no difficulty in learning appetitive tasks, which consisted in developing a preference for a rewarding corner in the IntelliCage. Indeed, they were more strongly "addicted" to sugar than sham mice but temporarily failed to relearn the location of rewarding sites after corner switching (reversal learning). They were mildly overactive in some tasks but without disruptions of circadian rhythms or impact on social structure. They adopted a strategy to maintain licking with fewer nosepokes, presumably trying to avoid mechanical stimulation of the snout. The results suggest that mice with DIONI develop strong aversive memories and some cognitive inflexibility, but create adaptive strategies to cope with the persistent trigeminal hypersensitivity.
三叉神经的炎症或损伤常伴有持续性面部疼痛及其后遗症。已经有许多模型被用来研究啮齿动物的三叉神经痛，但长期的行为后果尚不清楚。本研究描述了一种称为 DIONI 的眶下神经远端损伤模型，它包括眶下神经远端纤维的结扎和横断。我们使用冲突范式和光遗传学评估了伤害感受，并在 IntelliCage 中进行了一系列奖励、厌恶、空间、时间和竞争任务，以研究处于家庭笼环境中的小鼠群体的认知、昼夜节律和社会互动的多个方面。患有 DIONI 的小鼠出现冷觉和机械性痛觉过敏，以及对蓝光刺激的超敏反应。它们对厌恶刺激（来自上方的空气喷吹）保持持久的记忆，但在学习奖励任务时没有困难，这些任务包括在 IntelliCage 中发展对奖励角落的偏好。事实上，它们比假手术小鼠更强烈地“沉迷”于糖，但在角落切换后（反转学习）暂时无法重新学习奖励地点的位置。它们在一些任务中表现出轻微的过度活跃，但昼夜节律不受影响，也不会影响社会结构。它们采取了一种策略来保持较少的鼻触以保持舔舐，大概是试图避免对鼻子的机械刺激。结果表明，患有 DIONI 的小鼠会产生强烈的厌恶记忆和一些认知灵活性障碍，但会制定适应性策略来应对持续的三叉神经过敏。
