COMORBIDITY BETWEEN DEPRESSION AND OROFACIAL PAIN

描述（由申请人提供）：慢性疼痛的临床管理，包括与颞下颌疾病（TMD）相关的疼痛，一直具有挑战性，部分原因是相当多的慢性疼痛患者伴有心理和精神合并症，其中抑郁症是主要因素。虽然临床抑郁症长期以来一直与慢性疼痛有关，抗抑郁药通常用于慢性疼痛治疗，但抑郁症和慢性疼痛共病的潜在机制尚不清楚。迄今为止，还缺乏在同一动物中共同表达抑郁和口面部疼痛行为的临床前模型。我们最近的实验表明，与没有抑郁行为的正常Wistar大鼠相比，完全弗氏佐剂诱导的TMD疼痛行为在Wistar- kyoto （WKY）大鼠（Wistar大鼠的一种遗传变异，具有明显的抑郁行为）亚群中加剧。此外，在WKY大鼠中，前扣带皮层给予褪黑素可以防止TMD疼痛行为的加剧，同时改善抑郁行为。这些初步结果表明，比较有和没有抑郁行为的动物的疼痛行为可能是研究抑郁症和慢性疼痛之间关系的有用方法，并探索抑郁症和慢性疼痛的新治疗方案。因此，本应用的目标是：1)探索和评估共同表达口腔面部疼痛和抑郁行为的动物模型；2)使用动物模型和新的药理学方法来检查改善抑郁行为是否会导致疼痛行为的同时减少。我们将使用行为学和药理学工具，原位杂交，免疫细胞化学，Western blot，实时RT-PCR和酶联免疫吸附法来实现三个特定目标：1)探索和评估抑郁症和TMD联合疼痛行为的动物模型；2)探讨褪黑素对抑郁症和TMD疼痛行为的影响；3)研究褪黑激素水平和脑褪黑激素受体表达与抑郁和TMD疼痛行为的关系。这项工作的成功完成将为一个新的临床前模型提供重要信息，该模型可用于研究抑郁症和慢性疼痛之间的相互作用，并寻找治疗慢性疼痛和抑郁症的新治疗策略。

DESCRIPTION (provided by applicant): Clinical management of chronic pain, including pain related to temporomandibular disorders (TMD), has been challenging in part because a considerable number of chronic pain patients have accompanying psychological and psychiatric comorbidities in which depression is a major contributing factor. While clinical depression has long been linked to chronic pain and antidepressants are commonly used in chronic pain management, the mechanisms underlying the comorbidity between depression and chronic pain remain unclear. To date, there has been a lack of preclinical models that co-express depression and orofacial pain behaviors in same animals. Our recent experiments showed that TMD pain behaviors induced by complete Freund's adjuvant were exacerbated in a subset of Wistar-Kyoto (WKY) rats, a genetic variant of Wistar rats with demonstrable depression behavior, as compared with normal Wistar rats absent of depression behavior. Moreover, melatonin administered into the anterior cingular cortex prevented the exacerbation of TMD pain behaviors with a concurrent improvement of depression behavior in WKY rats. These preliminary results suggest that comparing pain behaviors in animals with and without depression behavior could be a useful approach to investigate the relationship between depression and chronic pain and to explore new treatment options for both depression and chronic pain. Thus, the goals of this application are 1) to explore and evaluate animal models that co-express orofacial pain and depression behaviors and 2) to use the animal model and a new pharmacological approach to examine whether improving depression behavior would result in a concurrent reduction of pain behaviors. We will use behavioral and pharmacological tools, in situ hybridization, immunocytochemistry, Western blot, real-time RT-PCR, and enzyme-linked immunosorbent assay to accomplish three specific aims: 1) to explore and evaluate animal models of combined depression and TMD pain behaviors; 2) to examine the effects of melatonin on depression and TMD pain behaviors; and 3) to examine changes in the melatonin level and brain melatonin receptor expression in relation to depression and TMD pain behaviors. The successful completion of this work will provide important information on a new preclinical model that could be used to examine interactions between depression and chronic pain and to search for novel therapeutic strategies for treating both chronic pain and depression.