COMORBIDITY BETWEEN DEPRESSION AND OROFACIAL PAIN

描述(申请人提供)：慢性疼痛的临床管理，包括与颞下颌关节紊乱病(TMD)相关的疼痛，一直是具有挑战性的，部分原因是相当多的慢性疼痛患者伴有心理和精神并存，其中抑郁是一个主要因素。虽然临床抑郁症长期以来被认为与慢性疼痛有关，抗抑郁药物也常用于慢性疼痛的治疗，但抑郁症和慢性疼痛共病的潜在机制仍不清楚。到目前为止，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-京都(WKY)大鼠中的一部分加剧。WKY大鼠是Wistar大鼠的一个基因变体，具有明显的抑郁行为。此外，在WKY大鼠的前扣带回皮质注射褪黑激素可预防TMD疼痛行为的恶化，同时改善抑郁行为。这些初步结果表明，比较有无抑郁行为的动物的疼痛行为可能是一种有用的方法，可以研究抑郁与慢性疼痛之间的关系，并探索抑郁症和慢性疼痛的新治疗选择。因此，这项应用的目标是1)探索和评估共同表达口面部疼痛和抑郁行为的动物模型，以及2)使用该动物模型和一种新的药理学方法来检验改善抑郁行为是否会同时导致疼痛行为的减少。我们将使用行为和药理学工具、原位杂交、免疫细胞化学、Western印迹、实时RT-PCR和酶联免疫吸附试验来实现三个具体目标：1)探索和评估抑郁症和TMD疼痛行为的动物模型；2)研究褪黑素对抑郁和TMD疼痛行为的影响；3)研究与抑郁和TMD疼痛行为相关的褪黑素水平和脑褪黑素受体表达的变化。这项工作的成功完成将为一种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.