Influencing factors of brain alterations in chronic pain

近年来，临床参数和成像数据以及预测性生物标志物的关联使得对慢性疼痛的神经生物学有了有价值的见解。慢性背痛患者的大脑在内侧前额叶皮层、扣带回和脑岛前部的灰质中表现出特征性的体积减少。然而，各种疼痛综合征的结果仍然非常不一致，这在很大程度上是由于个体研究的组规模太小。在频繁的疼痛障碍的情况下，也可以使用基于人群的研究分析，可以提供必要的群体规模。我们打算通过拟议的项目来缩小这一差距。我们分析了SHIP研究（波美拉尼亚健康研究）的两个纵向人群队列和纵向临床数据集中基于体素的灰质体积（GMV）的体积。该项目的总体目标是通过在两个广泛的基于人群的队列中使用各种疼痛综合征的现有信息来表征慢性疼痛的神经生物学。此外，我们用临床研究补充了基于人群队列的观察结果。这些患者包括颅下颌骨疼痛和上肢疼痛相关的复杂区域疼痛综合征（CRPS）患者，这是一种神经性疼痛综合征。基于人群的队列研究的优势在于数据的全面收集，在常见疾病的情况下，还可以记录生物标志物，从而预测谁将在调查后出现这些综合征。患者检查的优势在于采用循证治疗方法进行具体调查。这反过来又使得确定治疗应答者的纵向预测因子成为可能。这两个队列的特殊之处在于，他们与大量没有急性和慢性疼痛的匹配对照者一起在相同的MRI上进行测量。这使得数据池具有独特的同质性。此外，这两个队列可以更仔细地观察所有综合征中GMV的共同变化，观察每种综合征的具体变化，还可以比较其他精神疾病的具体变化，这些疾病在个体症状（抑郁和焦虑）方面与慢性疼痛有很大的重叠。最终，在记录大量参数的情况下，还可以通过中介分析计算出与灰质变化的关系。总之，该项目申请的纵向可用数据集提供了一个独特的机会来识别慢性疼痛的生物标志物，并测试它们的特异性，特别是关于GMV的改变。

Associations of clinical parameters and imaging data as well as predictive biomarkers have enabled valuable insights into the neurobiology of chronic pain in recent years. The brains of patients with chronic back pain show characteristic volume reductions in the gray matter of the brain in the medial prefrontal cortex, the cingulate gyrus, and the anterior insula. However, the results for various pain syndromes are still very inconsistent, which can largely be attributed to group sizes that are too small in the individual studies.In the case of frequent pain disorders, analyzes from population-based studies can also be used that can provide the necessary group sizes. With the proposed project we intend to close this gap. We analyze the volume of the gray matter volume (GMV) based on voxels in two longitudinal population-based cohorts of the SHIP study (Study of health in Pomerania) and in longitudinal clinical data sets. The overall goal of this project is to characterize the neurobiology of chronic pain by using existing information on various pain syndromes in two extensive population-based cohorts. In addition, we supplement the observations made in population-based cohorts with clinical studies. These include patients with craniomandibular pain and patients with upper extremity pain associated with complex regional pain syndrome (CRPS), which is a neuropathic pain syndrome. The advantage of the population-based cohort studies lies in the comprehensive collection of data, which in the case of frequently occurring diseases also enables the recording of biomarkers that can predict who will develop these syndromes in the post-survey period. The advantage of the patient examinations lies in the specific surveys with an evidence-based therapy method. This in turn makes it possible to determine longitudinal predictors for therapy responders. What is specific about both cohorts is that they were measured on the same MRI together with a large number of matched controls free of acute and chronic pain. This enables a unique homogeneity of the data pool. In addition, both cohorts enable a closer look at the common changes in GMV in all syndromes, a look at specific changes for each individual syndrome, but also a comparison of the specific changes to other mental illnesses that show large overlaps with chronic pain with regard to individual symptoms (depression and anxiety). Ultimately, with the large number of parameters recorded, relations with changes in gray matter can also be calculated by means of mediation analyzes. In summary, the project applied for with the longitudinally available data sets offers a unique opportunity to identify biomarkers for chronic pain and to test their specificity- especially with respect to GMV alterations.