Novel target identification for treatment of chronic overlapping pain using multimodal brain imaging

使用多模态脑成像治疗慢性重叠痛的新靶点识别

基本信息

批准号：
10612148
负责人：
Ohannes Kevork Melemedjian
金额：
$ 30.03万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10612148
关键词：
Acute Address Affect American Animal Model Animals Anterior Area Arthralgia Automobile Driving Brain Brain imaging Characteristics Chronic Chronic low back pain Chronic stress Clinic Clinical Country Cross Bite Data Set Disease Electrodes Female Fibromyalgia Functional Magnetic Resonance Imaging Future Goals Housing Hypersensitivity Implanted Electrodes Individual Inflammation Injury Irritable Bowel Syndrome Malocclusion Masseter Muscle Mastication Measures Medical Methods Modeling Modification Neuraxis Neurobiology Operative Surgical Procedures Opioid Orofacial Pain Pain Pain management Patients Peripheral Pharmacological Treatment Physicians Rattus Reporting Rest Stress Symptoms Temporomandibular Joint Temporomandibular Joint Disorders Testing Therapeutic Intervention Tissues Translating Unnecessary Surgery Visceral Visceral pain Woman chronic pain management chronic painful condition comorbidity cost epidemiologic data experimental study interdisciplinary approach male multimodality new therapeutic target novel opioid epidemic orofacial pain model parent project perceived stress response therapeutically effective tissue stress

项目摘要

Summary Chronic overlapping pain conditions (COPCs) are idiopathic pain conditions that have minimal identifiable origins in organic disease and represent a highly significant pain management challenge for physician and patient. They occur in tens of millions of Americans with annual costs exceeding $100 billion. Epidemiological data indicate many of these conditions overlap in presentation in the same patient, with odds of presenting 2 or more conditions exceeding 50%. Often spatially separate areas of the body are affected (e.g., temporomandibular disorder (TMD) and irritable bowel syndrome (IBS)), which strongly suggests the involvement of central nervous system mechanisms. Additionally, stress triggers or exacerbates many of these conditions, which occur more frequently or exclusively in women. The convergence of pain from different peripheral tissues and perceived stress most likely occurs in the brain. We have developed an animal model of comorbid pain conditions that involves masseter muscle inflammation plus stress to induce chronic visceral hypersensitivity modeling the pain in patients with TMD and IBS. The purpose of this supplemental project is to refine this comorbid pain model for further use in our novel therapeutic target discovery project. We propose a more natural orofacial condition, malocclusion producing a unilateral anterior crossbite, which has been reported to evoke temporomandibular joint pain. This will be combined with less invasive methods to measure visceral hypersensitivity, using referred pain rather than the visceromotor response, eliminating the need for surgery to implant electrodes and single housing to protect electrode leads from cagemates. These conditions are proposed to refine the model more closely approximating conditions that might contribute to chronic overlapping pain in order to gain a mechanistic understanding and aid discovery of novel therapeutic targets.

概括慢性重叠疼痛状况（COPC）是特发性疼痛状况，可识别最小起源于有机疾病，代表了医生和病人。它们发生在数千万的美国人中，每年成本超过1000亿美元。流行病学数据表明，在同一患者中，其中许多条件在介绍中重叠，呈现2或更多的条件超过50％。通常在空间上分开的身体受到影响（例如，颞下颌疾病（TMD）和肠易激综合症（IBS）），强烈建议中枢神经系统机制的参与。此外，压力触发或加剧了其中的许多妇女中更频繁或完全发生的情况。来自不同的疼痛的收敛周围组织和感知的压力很可能发生在大脑中。我们已经开发了一个动物模型合并症疼痛条件，涉及咬肌肌肉炎症加压力以诱导慢性内脏高敏性对TMD和IBS患者的疼痛进行建模。这个补充项目的目的是完善这种合并症疼痛模型，以在我们新颖的治疗目标发现项目中进一步使用。我们提出了一个更自然的口肤状况，出现单侧前咬合的变质咬合，这已经是据报道引起颞下颌关节疼痛。这将与较少的侵入性方法相结合内脏超敏反应，使用引用的疼痛而不是内脏运动反应，消除了对手术到植入物电极和单个外壳，以保护电极导线免受cagemates的侵害。这些条件提出提出更接近近似条件的模型，这可能有助于慢性重叠疼痛以获得机械理解并有助于发现新型治疗靶标。