Stratifying Chronic Pain Patients By Pathological Mechanism- A Multimodal Investigation Using Functional MRI, Psychometric And Clinical Assessment

按病理机制对慢性疼痛患者进行分层 - 使用功能 MRI、心理测量和临床评估的多模式研究

• 批准号: MR/N026969/1
• 负责人: Stephen McMahon
• 金额: $ 346.33万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FN026969%2F1
• 关键词: Stratifying; Chronic; Pain; Patients; Pathological

Approximately one person in five suffers with pain every day. Despite our best efforts we often struggle even to partly alleviate their pain. One reason is that current diagnoses are based upon symptoms, but the same symptoms can occur for different reasons. If we could diagnose pain based upon 'mechanisms', the biological processes underlying symptoms, then patients might get more precise treatment earlier.Several mechanisms can be faulty in chronic pain. They can be 'peripheral'- when sensors in the body that detect danger persistently send messages via the spinal cord to the brain. Sometimes 'crossed-wires' occur in the spine, where messages representing touch become scrambled, resulting in an incorrect or amplified pain signal- 'central sensitisation'. These processes might be due to disease (e.g. osteoarthritis (OA)) or because of nerve damage-'neuropathy'. Brain imaging has told us that changes in the way parts of the brain communicate with one another -'connectivity'- predicts transition to chronic pain, but we don't know whether connectivity differences cause pain or are a 'knock-on' effect of dysfunction elsewhere; perhaps peripherally or in the cord. Finally, pain control systems in the base of the brain (brainstem)- the 'descending modulatory system'- can fail, producing symptoms similar to central sensitisation. One or all these mechanisms might be involved in patients with chronic pain. As the symptoms can look the same we don't currently know which.This project aims to predict the mechanisms underlying individual patients with chronic pain of the face or upper limb. We will use computerised pattern recognition (PR) techniques to determine which combination of clinical assessments (examinations, interviews, questionnaires); specialised nervous system tests and brain/spine imaging techniques best detect the underlying pathophysiological mechanisms. Historically it has been difficult to get clear 'functional' images of the brainstem and spine during rest and stimulation but we now have new methods to help solve these problems. First, we will use electrical stimulation in the arms of healthy, pain-free people to see how the periphery transmits a normal ongoing pain signal. By changing the characteristics of the stimulation we can also temporarily create central sensitisation in the spine. In the face, we can examine pain due to peripheral and central sensitisation after wisdom tooth surgery. We can use an anaesthetic injection to 'block' the peripheral signal to look at central sensitisation only in these patients. Rarely, but sometimes wisdom tooth surgery produces nerve damage, leading to chronic facial pain. We will also study these patients too, again using anaesthetic injections to look at the peripheral and central signals separately. We will also study patients with chronic arm pain due to OA. Historically OA was considered a 'peripheral' disease, but some patients may also have 'central' changes, which we will determine in the brain and spine. Finally, we will use a technique called 'Conditioned Pain Modulation' (CPM) to assess, in all patients and healthy people, how well their 'descending modulatory' pain control systems are working.We will capitalise on all of these clinical data (imaging, examination, questionnaires) and use PR to develop distinct 'fingerprints' that classify peripheral and central pain mechanisms. We will apply the classifier in each chronic face and arm patient to make predictions about their individual underlying pathophysiology. Similarly, a second classifier will be trained to recognise 'normal' versus 'abnormal' descending modulatory pain control in each chronic pain patient. Success in this project will help us get the best treatment, more quickly to suit the needs of each patient in persistent pain. The new knowledge that we generate about how the brain and spine represent these mechanisms will also stimulate the development of much-needed new treatments.

大约每五个人中就有一个人每天遭受疼痛。尽管我们尽了最大的努力，但我们往往很难减轻他们的痛苦。一个原因是，目前的诊断是基于症状，但相同的症状可能会出现不同的原因。如果我们能够根据“机制”，即症状背后的生物学过程来诊断疼痛，那么患者可能会更早得到更精确的治疗。它们可以是“外围的”--当身体中检测到危险的传感器持续地通过脊髓向大脑发送信息时。有时，“交叉线”发生在脊柱中，代表触摸的信息变得混乱，导致错误或放大的疼痛信号-“中枢敏感化”。这些过程可能是由于疾病（如骨关节炎（OA））或因为神经损伤-“神经病变”。大脑成像告诉我们，大脑各部分相互交流的方式的变化--“连接性”--预示着向慢性疼痛的转变，但我们不知道连接性的差异是否会导致疼痛，或者是其他地方功能障碍的“连锁反应”;也许是外周或脊髓。最后，大脑底部（脑干）的疼痛控制系统-“下行调节系统”-可能会失败，产生类似于中枢敏感的症状。这些机制中的一种或全部可能与慢性疼痛患者有关。由于症状可能看起来相同，我们目前还不知道是哪种。该项目旨在预测面部或上肢慢性疼痛患者的潜在机制。我们将使用计算机模式识别（PR）技术来确定临床评估（检查，访谈，问卷调查）的组合;专门的神经系统测试和脑/脊柱成像技术最好地检测潜在的病理生理机制。从历史上看，在休息和刺激期间很难获得脑干和脊柱的清晰“功能”图像，但我们现在有新的方法来帮助解决这些问题。首先，我们将在健康、无痛的人的手臂上使用电刺激，看看外周如何传递正常的持续疼痛信号。通过改变刺激的特性，我们还可以暂时在脊柱中产生中枢敏化。在面部，我们可以检查由于智齿手术后的外周和中枢敏感化引起的疼痛。我们可以使用麻醉剂注射来“阻断”外周信号，以观察仅在这些患者中的中枢致敏。很少，但有时智齿手术会造成神经损伤，导致慢性面部疼痛。我们也将研究这些患者，同样使用麻醉剂注射来分别观察外周和中枢信号。我们还将研究因OA引起的慢性手臂疼痛患者。从历史上看，OA被认为是一种“外周”疾病，但有些患者也可能有“中枢”变化，我们将在大脑和脊柱中确定。最后，我们将使用一种名为“条件性疼痛调节”（CPM）的技术来评估所有患者和健康人的“下行调节”疼痛控制系统的工作情况。我们将利用所有这些临床数据（成像、检查、问卷），并使用PR来开发区分外周和中枢疼痛机制的不同“指纹”。我们将在每个慢性面部和手臂患者中应用分类器，以预测其个体潜在的病理生理学。类似地，将训练第二分类器以识别每个慢性疼痛患者中的“正常”与“异常”下行调节性疼痛控制。这个项目的成功将帮助我们获得最好的治疗，更快地满足每个持续疼痛患者的需求。我们对大脑和脊柱如何代表这些机制的新知识也将刺激急需的新治疗方法的发展。

项目成果

Towards optimising experimental quantification of persistent pain in Parkinson's disease using psychophysical testing.

• DOI: 10.1038/s41531-021-00173-y
• 发表时间: 2021-03-17
• 期刊: NPJ Parkinson's disease
• 作者: Bannister K;Smith RV;Wilkins P;Cummins TM
• 通讯作者: Cummins TM

Denoising spinal cord fMRI data: Approaches to acquisition and analysis

• DOI: 10.1016/j.neuroimage.2016.09.065
• 发表时间: 2017-07-01
• 期刊: NEUROIMAGE
• 影响因子: 5.7
• 作者: Eippert, Falk;Kong, Yazhuo;Brooks, Jonathan C. W.
• 通讯作者: Brooks, Jonathan C. W.

Comparing the test-retest reliability of resting-state functional magnetic resonance imaging metrics across single band and multiband acquisitions in the context of healthy aging.

• DOI: 10.1002/hbm.26180
• 发表时间: 2023-04-01
• 期刊: HUMAN BRAIN MAPPING
• 影响因子: 4.8
• 作者: Cahart, Marie-Stephanie;O'Daly, Owen;Giampietro, Vincent;Timmers, Maarten;Streffer, Johannes;Einstein, Steven;Zelaya, Fernando;Dell'Acqua, Flavio;Williams, Steven C. R.
• 通讯作者: Williams, Steven C. R.

Assessment of Somatosensory Function and Self-harm in Adolescents.

• DOI: 10.1001/jamanetworkopen.2021.16853
• 发表时间: 2021-07-01
• 期刊: JAMA network open
• 影响因子: 13.8
• 作者: Cummins TM;English O;Minnis H;Stahl D;O'Connor RC;Bannister K;McMahon SB;Ougrin D
• 通讯作者: Ougrin D

Test-retest reliability of time-varying patterns of brain activity across single band and multiband resting-state functional magnetic resonance imaging in healthy older adults.

• DOI: 10.3389/fnhum.2022.980280
• 发表时间: 2022
• 期刊: FRONTIERS IN HUMAN NEUROSCIENCE
• 影响因子: 2.9
• 作者: Cahart, Marie-Stephanie;Dell'Acqua, Flavio;Giampietro, Vincent;Cabral, Joana;Timmers, Maarten;Streffer, Johannes;Einstein, Steven;Zelaya, Fernando;Williams, Steven C. R.;O'Daly, Owen
• 通讯作者: O'Daly, Owen