From the NYU Orofacial and Head Pain Program, Department of Oral and Maxillofacial Pathology, Radiology and Medicine, New York, NY, USA (M. Romero-Reyes); UCLA Headache Research and Treatment Program, Department of Neurology, David Geffen School of Medicine, Los Angeles, CA, USA (M. Romero-Reyes, E. Nguyen, A. Vijjeswarapu, B. Hom, H-W. Dong, and A.C. Charles); UCSF Headache Group, Department of Neurology, San Francisco, CA, USA (S. Akerman); Laboratory of Neuro Imaging (LONI), Department of Neurology, David Geffen School of Medicine, Los Angeles, CA, USA (H-W. Dong).
Headache. 2013 Jan;53(1):137-151. doi: 10.1111/j.1526-4610.2012.02226.x. Epub 2012 Jul 25.
To develop a translational mouse model for the study and measurement of non-evoked pain in the orofacial region by establishing markers of nociceptive-specific grooming behaviors in the mouse.
Some of the most prevalent and debilitating conditions involve pain in the trigeminal distribution. Although there are current therapies for these pain conditions, for many patients, they are far from optimal. Understanding the pathophysiology of pain disorders arising from structures innervated by the trigeminal nerve is still limited, and most animal behavioral models focus on the measurement of evoked pain. In patients, spontaneous (non-evoked) pain responses provide a more accurate representation of the pain experience than do responses that are evoked by an artificial stimulus. Therefore, the development of animal models that measure spontaneous nociceptive behaviors may provide a significant translational tool for a better understanding of pain neurobiology.
C57BL/6 mice received either an injection of 0.9% saline solution or complete Freund's adjuvant into the right masseter muscle. Animals were video-recorded and then analyzed by an observer blind to the experiment group. The duration of different facial grooming patterns performed in the area of injection were measured. After 2 hours, mice were euthanized and perfused, and the brainstem was removed. Fos protein expression in the trigeminal nucleus caudalis was quantified using immunohistochemistry to investigate nociceptive-specific neuronal activation. A separate group of animals was treated with morphine sulfate to determine the nociceptive-specific nature of their behaviors.
We characterized and quantified 3 distinct patterns of acute grooming behaviors: forepaw rubbing, lower lip skin/cheek rubbing against enclosure floor, and hindpaw scratching. These behaviors occurred with a reproducible frequency and time course, and were inhibited by the analgesic morphine. Complete Freund's adjuvant-injected animals also showed Fos labeling consistent with neuronal activation in nociceptive-specific pathways of the trigeminal nucleus after 2 hours.
These behaviors and their correlated cellular responses represent a model of trigeminal pain that can be used to better understand basic mechanisms of orofacial pain and identify new therapeutic approaches to this common and challenging condition.
通过建立小鼠伤害性感受特异性梳理行为标志物，开发用于研究和测量口腔面部区域非诱发性疼痛的转化性小鼠模型。
一些最常见和使人虚弱的疾病涉及三叉神经分布区的疼痛。尽管目前有针对这些疼痛疾病的治疗方法，但对许多患者来说，这些方法远非最佳。对源自三叉神经支配结构的疼痛障碍的病理生理学的理解仍然有限，并且大多数动物行为模型侧重于测量诱发性疼痛。在患者中，自发（非诱发性）疼痛反应比由人工刺激引起的反应更能准确地反映疼痛体验。因此，开发测量自发伤害性行为的动物模型可能为更好地理解疼痛神经生物学提供一个重要的转化工具。
C57BL/6 小鼠右咬肌注射 0.9%生理盐水或完全弗氏佐剂。对动物进行视频记录，然后由对实验分组不知情的观察者进行分析。测量注射区域内不同面部梳理模式的持续时间。2 小时后，处死并灌注小鼠，取出脑干。使用免疫组织化学方法定量测量三叉神经尾核中 Fos 蛋白的表达，以研究伤害感受特异性神经元激活。另一组动物用硫酸吗啡处理，以确定其行为的伤害感受特异性。
我们描述并量化了 3 种不同的急性梳理行为模式：前爪摩擦、下唇皮肤/脸颊摩擦围栏地板、后爪搔抓。这些行为以可重复的频率和时间进程发生，并且被阿片类镇痛药吗啡抑制。完全弗氏佐剂注射的动物在 2 小时后也表现出 Fos 标记，这与三叉神经核中伤害感受特异性通路的神经元激活一致。
这些行为及其相关的细胞反应代表了一种三叉神经疼痛模型，可用于更好地理解口腔面部疼痛的基本机制，并确定这种常见且具有挑战性的疾病的新治疗方法。
