Identifying pain-specific connectivity in the human brain

我们都经历过痛苦。它标志着潜在的伤害，包括感觉、情感、动机和认知维度，必须整合这些维度才能做出适当的反应。使用功能磁共振成像(FMRI)的脑成像研究一再表明，让个人受到痛苦的刺激会导致大脑活动的一致模式。然而，这种模式实际上并不是疼痛特有的，这种模式与触摸刺激没有什么区别。这是因为观察到的模式代表了疼痛吸引我们注意力的程度，即疼痛的突出程度。因此，还没有一个特定于疼痛的大脑区域，或一组大脑区域。尽管疼痛和触摸的激活模式难以区分，但这两种刺激的感觉非常不同，因此在大脑中肯定有不同的表示。大脑区域并不是孤立地运作的。它们形成网络来整合信息并产生感知体验和行为。因此，尽管触碰和疼痛激活了相同的大脑区域，但这些区域可能正在与不同的区域形成网络。确定这种情况是否属实，可能会揭示大脑感知疼痛的基本机制。这项建议的总体目标是确定一种痛觉机制。为了实现这一点，我们将识别疼痛和触摸刺激时的网络差异，这两种刺激的显著程度是一致的。然而，鉴于疼痛和触摸在感知上是不同的，疼痛本质上是令人不快的，而触摸不是，确定触摸和疼痛之间的大脑差异是否与不愉快有关，而不是疼痛本身，这一点很重要。回答这个问题的一种方法是比较不同形式的令人不快的刺激引发的大脑活动。因此，这项研究的第二个目的是比较已识别的疼痛连接性1是否通过三种不同的方式编码令人不快的刺激：视觉、触觉和伤害性。第三，疼痛特异性连接的强度可能与感受到的疼痛的强度有关。这项研究的第三个目的是测试疼痛特异性连接是否显示出对不同刺激强度的分级反应。最后，我们将使用新的结构脑成像技术来确定所观察到的疼痛特异性连接是否存在结构基础。这些研究将极大地促进我们对疼痛系统的基本了解，并对健康研究人员开发疼痛生物标记物和寻找新的治疗标记物具有深远的翻译影响。

We have all experienced pain. It signals potential injury, and comprises sensory, emotional, motivational and cognitive dimensions, which must be integrated to mount an appropriate response. Brain imaging studies using functional magnetic resonance imaging (fMRI) have repeatedly shown that subjecting individuals to painful stimuli results in a consistent pattern of brain activity. However, this pattern is not pain specific in fact, this pattern is indistinguishable from a touch stimulus. This is because the observed pattern represents the extent to which pain captures our attention i.e., pain's salience. As such, there has yet to be a pain-specific brain region, or set of brain regions. Although the activation pattern is indistinguishable between pain and touch, these stimuli feel very different, and thus must have different representations in the brain.Brain regions do not function in isolation. They form networks to integrate information and produce perceptual experiences and behaviour. Therefore, although the same sets of brain regions are activated by touch and pain, these regions may be forming networks with different regions. Determining if this is the case could reveal a fundamental mechanism by which pain is perceived in the brain. The overall aim of this proposal is to identify a mechanism for pain perception. To achieve this, we will identify network differences during painful and touch stimuli, that have been matched for salience. However, given that pain and touch are perceptually different pain is inherently unpleasant, whereas touch is not it is important to determine whether brain differences between touch and pain are related to unpleasantness, rather than pain itself. One way to answer this question is to compare brain activity elicited by unpleasant stimuli from different modalities. Therefore, the second aim of this study is to compare whether the identified pain connectivity 1 encodes unpleasant stimuli across three different modalities: visual, tactile and nociceptive. Third, the strength of pain-specific connectivity may be related to the intensity of the pain perceived. The third aim of this study is to test whether the pain specific connectivity shows a graded response to different stimulus intensities. Finally, we will determine whether there is a structural basis for the observed pain-specific connectivity using novel structural brain imaging techniques. These studies will greatly advance our fundamental understanding of the pain system, and have profound translational impact for health researchers to develop a biomarker for pain, and identify novel therapeutic markers.