Tissue Damage and Pain - Modelling Cutting Behavior in BPD

本项目的总体目标是阐明BPD患者非自杀性自伤（NSSI）的神经生物学机制。除了疼痛处理，NSSI的方面包括组织损伤（最常见的NSSI形式是切割），看到血液的视觉影响，以及伤害是自己造成的而不是其他造成的。在第一个资助期的研究1中，我们研究了组织损伤对应激调节的影响，并开发了一种替代刺激，该刺激引起的感觉和情感反应与组织损伤引起的反应非常相似。这种刺激是一种非侵入性机械“刀片”，其疼痛强度与切口刺激相匹配。在研究2中，我们比较了切口刺激对BPD患者应激水平的影响，机械刀片刺激和假对照刺激（无痛触摸）。中期分析显示，与假刺激相比，切口和刀片后的应力水平降低趋势更强，机械刀片和切口的张力降低时间过程相似。此外，初步研究1）调查了除了经历疼痛之外，看到（人造）血液的体验对紧张度降低的影响，以及2）使用MR光谱来量化疼痛处理大脑区域中的谷氨酸盐和GABA水平。由于刀片刺激显示出与切口诱导的疼痛特征和应力调节特性非常相似的疼痛特征和应力调节特性，因此将用于第二个资助期的研究，该研究有两个主要目标。首先，我们的目标是进一步阐明神经化学和神经功能机制相关的抗伤害性BPD，使用最近建立的神经影像学方法。全脑回波平面光谱成像将用于确定疼痛处理区域的谷氨酸代谢，并测量后额叶中的GABA和谷氨酸水平。将在刀片刺激前后进行伪连续动脉自旋标记，其允许在单次刺激后对疼痛处理区域中的血流进行绝对量化。在该项目的第二部分，目前患有NSSI的患者将被随机分为四组，以研究看到人造血液和自我应用疼痛刺激与研究者应用的压力调节效果。

The overall aim of this project is the elucidation of neurobiological mechanisms underlying nonsuicidal self-injury (NSSI) in BPD. In addition to pain processing, aspects of NSSI include tissue damage (the most frequent form of NSSI being cutting), the visual impact of seeing blood, and the perspective of the injury as being self-inflicted rather than other-inflicted. In Study 1 of the first funding period, we investigated the influence of tissue injury on stress regulation, and developed a surrogate stimulus that evoked sensory and affective responses that were very similar to those evoked by tissue injury. This stimulus, a non-invasive mechanical "blade", was matched for pain intensity with an incision stimulus. In Study 2, we compared the effects of the incision stimulus on stress levels in BPD patients, the mechanical blade stimulus, and a sham control stimulus (non-painful touch). Interim analysis has revealed a trend for stronger reduction of stress levels following incision and blade compared to the sham stimulus, and similar time courses of tension reduction for the mechanical blade and for incision. In addition, pilot studies have 1) investigated the influence on tension reduction of the experience of seeing (artificial) blood in addition to experiencing pain, and 2) used MR spectroscopy to quantify glutamate and GABA levels in pain-processing brain regions. As the blade stimulus showed both pain-characteristics and stress-regulation properties that were very similar to those induced by incision, it will be used in the studies of the second funding period, which has two major objectives. First, we aim to further elucidate neurochemical and neurofunctional mechanisms related to antinociception in BPD, using recently established neuroimaging methods. Whole-brain echo-planar sprectroscopic imaging will be used to determine glutamate metabolism in pain-processing regions, and GABA and glutamate levels in the posterior insula will be measured. Pseudo-continuous Arterial Spin Labeling, which allows absolute quantification of blood flow in pain-processing regions following single stimuli, will be conducted before and after blade stimulation. In the second part of the project, patients with current NSSI will be randomized into four groups in order to investigate the stress-regulating effects of seeing artificial blood and of self-application of the pain stimulus vs. application by an investigator.