A Novel Gnawing Assay to Quantify Nociception in Models of Chronic Orofacial Pain

描述(申请人提供)：慢性口腔面部疼痛影响10%的美国人，目前还没有有效的治疗方法。最常见和最严重的口腔面部疼痛包括头颈部癌症疼痛、TMJ疼痛和咀嚼肌肉疼痛。口腔面部疼痛患者的主要功能问题是咀嚼疼痛。然而，没有动物行为测试可以量化伤害性感觉对口腔功能的影响，并与患者的症状相平行。我们假设慢性口面部疼痛会产生可量化的咀嚼变化。此外，我们假设咬合功能的降低可以用来衡量伤害性感受。为了验证这些假设，我们设计、定制并试点测试了一种客观测量啮齿动物咬合功能的新型设备。在这个项目中，我们将使用我们的新设备来量化头颈癌疼痛、TMJ疼痛和咀嚼肌肉疼痛动物模型中显著的咬合功能损害。为了证实三种模型中改变的咬合功能是次要于疼痛的，我们将展示临床上用于治疗这些形式的慢性疼痛的药物的逆转。我们预计，通过提供一种不依赖于主观行为解释且不需要研究人员观察时间的定量功能伤害性分析，我们的工作将从根本上有助于提高对三叉神经系统伤害性感受机制的理解。

DESCRIPTION (provided by applicant): Chronic orofacial pain affects 10% of Americans and there currently is no effective treatment. The most common and most severe forms of orofacial pain include head and neck cancer pain, TMJ pain and masticatory muscle pain. The primary functional problem for orofacial pain patients is pain with chewing. However, there is no animal behavioral assay that quantifies the impact of nociception on oral function and that parallels the symptoms of patients. We hypothesize that chronic orofacial pain produces quantifiable masticatory changes. Moreover, we hypothesize that reduced gnawing function can be used as a measure of nociception. To test these hypotheses we have designed, custom built and pilot tested a novel device that objectively measures gnawing function in rodents. In this project we will use our novel device to quantify significant impairment of gnawing function in animal models of head and neck cancer pain, TMJ pain and masticatory muscle pain. To confirm that the altered gnawing function in the three models is secondary to pain we will demonstrate reversal with agents used clinically to treat these forms of chronic pain. We anticipate that our work will contribute fundamentally to improved understanding of nociceptive mechanisms of the trigeminal system by providing a quantitative functional nociceptive assay that does not depend on subjective behavioral interpretation and does not require observational time by an investigator.