Name: 作者聚焦：慢性疼痛管理研究的方法和进展
Uploaded: 2024-01-05T14:00:00
Description: Read this Scientific Article Protocol about Author Spotlight: Towards Biomarker Development Using Neuroimaging as a Tool to Enhance the Understanding of the Neural Basis of Pain at JoVE.com

作者要感谢视觉和神经认知康复中心的研究人员的支持，包括Bruce Crosson博士和Lisa Krishnamurthy博士，他们对这项工作的投入。作者还感谢格蕾丝·英厄姆（Grace Ingham）在拍摄过程中提供的宝贵帮助。这项工作部分得到了美国退伍军人事务部康复研究与发展服务职业发展奖 IK2 RX003227（安娜伍德伯里）和中心拨款 5I50RX002358 的支持。资助者在研究设计、数据收集、管理、分析、解释或报告方面没有任何作用。

该研究是在埃默里大学 （IRB 112768） 和亚特兰大弗吉尼亚州机构审查委员会 （1585632-2;内部参考编号：003）以及亚特兰大退伍军人事务部研发委员会（董事会参考编号：3881）。所有受试者在参与本研究之前都给予了纳入的知情同意。有关研究方案时间表的视觉表示，请参阅 图 1）。
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/657...

评估颅脑电刺激对纤维肌痛的疗效

目前研究的方法不仅提供了对纤维肌痛的高效治疗方式的可能性，而且还提供了从疼痛症状特征的第一实例开始改善纤维肌痛诊断过程的机会。使用有源 CES 和假 CES，发现每个单独设备的类型取决于序列号和单独的密钥，允许受试者和研究人员在参与结束之前保持盲法，从而在评估管理期间保护内部有效性，并更清晰地展示设备和刺激的功效的临床图片81.增加探索功能连接神经?...

在许多现有的慢性疼痛状态中，最臭名昭著的难以诊断、临床评估和治疗的疾病之一是纤维肌痛。纤维肌痛是一种使人衰弱的慢性疼痛综合征，涉及慢性广泛性疼痛、身体机能下降、疲劳、心理情绪和睡眠障碍，以及各种躯体疾病，影响美洲约 2-3% 的普通人群（美国约 800 万人）1. 疾病的诊断在很大程度上依赖于患者对自己症状特征和疼痛体验的理解，如果没有临床医生和患者对疾病的正确理解，治疗方法就会失去相当大的疗效2.更好地定义纤维肌痛的起源和影响，以及指导纤维肌痛诊断和治疗的可靠临床生物标志物对于最好地服务于所有患者是必要的。
即使确诊，治疗过程的困难也只会增加。总体而言，慢性疼痛影响的个体比心脏病、糖尿病和癌症的总和还要多。其评估的主观性使其成为阿片类药物流行的主要驱动因素，特别是考虑到难以从物质使用障碍和寻求药物的行为中辨别出未完全治疗的身体疼痛3.2020 年，美国发生了 91,799 例药物过量死亡（比 2019 年增加 30%），阿片类药物被发现是这些死亡的主要原因（占 2020 年所有药物过量死亡人数的 74.8%）4。因此，慢性疼痛和纤维肌痛治疗需要非药物替代品来减缓阿片类药物的流行，这在自杀和阿片类药物使用障碍风险较高的退伍军人群体中尤为重要5.因此，非药物疗法和补充疗法通常被用作一线治疗6.
对新颖、有效的纤维肌痛干预措施的探索使许多研究人员和临床医生转向了无创脑刺激的方法，包括颅脑刺激。尽管导致疾病发展的病理生理机制尚未明确确定，但现有证据支持纤维肌痛是一种自主神经系统功能障碍和中枢（即大脑和脊髓）疼痛处理机制的疾病 7,8。刺激大脑的某些区域可能会导致这些处理区域的功能得到改善。重复经颅磁刺激 （rTMS） 和经颅直流电刺激 （tDCS） 与疼痛减轻有关，但也与激活部位头皮刺激、头痛和治疗设施外的无法接近有关9.无创迷走神经刺激 （nVNS） 可以通过刺激颈部或耳朵水平的皮肤来提供神经调控，具有治疗慢性疼痛的潜力，侵入性迷走神经刺激 （VNS） 已被证明可以改善慢性疼痛症状10。然而，侵入性和非侵入性 VNS 均未在文献中得到充分探索，也未得到充分验证可用于纤维肌痛治疗 11,12,13,14。
颅脑电刺激 （CES） 是一种非药物、非侵入性脑刺激治疗，包括通过放置在耳垂15 上的经皮电极施加脉冲交变微电流（小于 0.5 mA）。它非常容易获得，并且可以通过患者在自己的生活空间内使用的便携式设备进行传输。与其他颅脑刺激方法相比，非侵入性和患者在家中自我应用的便利性增加了 CES 作为广泛使用纤维肌痛治疗和疼痛自我管理的有益选择的潜力。它已被美国食品和药物管理局 （FDA） 批准用于治疗失眠、抑郁、焦虑和疼痛15。
目前的研究通过比较主动 CES（由真正的研究设备给药）与假 CES（由假研究设备给药）来评估 CES 作为纤维肌痛治疗方式的疗效。有一些初步证据支持使用 CES 治疗纤维肌痛等疼痛状况16,17。2001 年的一项研究对 60 名参与者进行了随机分配，随机接受主动或假 CES 组，为期 3 周，每天 60 分钟，结果显示，压痛点评分提高了 28%，一般疼痛评分提高了 27%，没有安慰剂效应18。尚未在退伍军人群体中对 CES 进行评估，也未在患有纤维肌痛的男性中进行充分评估。2018 年发表的一项由退伍军人事务部 （VA） 资助的 CES 系统评价得出结论，鉴于大多数试验样本量小、持续时间短且由于盲法不足而存在高偏倚风险，因此 CES 不足以对纤维肌痛产生临床重要影响。然而，该评价表明，CES不会引起严重的副作用，并且有低强度证据表明CES对焦虑和抑郁患者有适度的益处19。因此，有必要对这种 FDA 批准的低风险设备的使用进行进一步研究，特别是在纤维肌痛方面。
为了全面评估疗效，研究人员评估了身体健康状况以及神经生物标志物和疼痛体验。治疗慢性疼痛状态的目的是改善身体机能。纤维肌痛与对身体机能和患者对自己身体能力的感知的负面影响始终相关20.以前的研究利用简单的体能评估来确定耐力和活动能力，例如 6 分钟步行测试 （6MWT）20,21、五次坐立 （5TSTS）20，以及日常活动中各种承载能力和力量的测量22。为了考虑到标准措施，同时也减轻了 MRI 扫描前所需的剧烈活动量，研究小组使用 30 秒椅子坐立测试作为耐力和活动性的衡量标准，并使用二头肌卷曲和手握测试作为力量的衡量标准23.这些评估中每一项所需的运动在日常活动中都很常见，因此它是衡量人们在日常生活中身体机能如何的明确指标，无论是否接受治疗。
即使有主观疼痛评估和身体机能疗效测量，CES的机制也没有完全理解。先前的神经影像学研究通过探索CES对大脑网络连接的直接影响，寻求更好的理解。Feusner 等人 24 发现 CES 与 0.5 Hz 的皮质失活和 100 μA 的双侧额叶、顶叶和后中线区域刺激有关，并假设刺激频率可能比当前强度对皮质失活的影响更大。他们的小组发现对默认模式网络（DMN）的某些节点（但不是全部）有显着影响。作者认为，基于这些数据，CES可能会影响静息态功能连接。纤维肌痛和其他慢性疼痛状态已被证明会影响与疼痛和感知相关的区域的内在大脑连接25,26，因此改变功能连接的治疗可能被证明是有益和有效的。需要进一步探索日常治疗对临床改善的长期影响，以及大脑中死亡激活与先前观察到的脑电图频率降低的关系，以进一步理解治疗作用机制27。
静息态功能连接磁共振成像 （rs-fcMRI） 是一种神经成像方法，可以观察这些功能连接变化。纵向静息态 fMRI 使临床医生和研究人员能够建立静息态连通性的基线，并跟踪随时间推移对 CES 治疗方法的反应变化。它还有助于确定功能连接的变化如何与疼痛体验的差异相关联。纤维肌痛神经影像学的初步研究使用正电子发射断层扫描 （PET） 和单光子发射计算机断层扫描 （SPECT） 来检查大脑，但这两种技术在这方面都存在问题：SPECT 的分辨率低于 PET，并且 PET 扫描是侵入性的，这对于患有慢性疼痛的患者来说是不可取的。功能性磁共振成像 （fMRI） 扫描比 SPECT 具有更高的分辨率，但它们检查大脑活动对患者的特定动作或对刺激的感知28。rs-fcMRI 扫描可以勾勒出大脑区域之间的功能连接，并可能能够确定纤维肌痛存在的位置和方式以及最佳治疗方法28。
在当前阿片类药物流行的环境中，评估非药物治疗对纤维肌痛等疼痛状况的疗效至关重要，并且在检查慢性疼痛作为自杀的危险因素时都至关重要29,30，这在退伍军人中大大增加。此外，缺乏足够的疼痛临床生物标志物是一个公认的知识差距。在多个时间点结合使用行为测量和神经影像学来评估治疗反应是一种新的纤维肌痛评估方法，使用耳廓 CES 作为治疗方法也是如此。
该协议旨在通过调查 CES 对疼痛和身体功能结果的影响并评估神经影像学作为与 CES 治疗临床结果相关的预测和反应生物标志物的工具，从而解决纤维肌痛研究的差距31.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>3T Siemens MAGNETOM Prisma Scanner</td>
			<td>Siemens Healthineers</td>
			<td>N/A</td>
			<td>From Emory&#39;s website: &#34;The Siemens Magnetom Prisma 3T whole-body MR system is equipped with: a state-of-the art gradient system with a maximum (per axis) strength of 80 mT/m and slew rate of 200 T/m/sec 
			64 independent RF receiver channels capable of 204 receiver connections 
			a 2-channel RF transmitter. Multiple coils are available, including: a 64-channel head/neck coil with 52 channels for imaging of the head region 
			a 32-channel head-only coil 
			a 20-channel head/neck coil with 16 channels for head 
			spine array coil 
			flexible chest coil 
			large and small flexible coil for extremity imaging.</td>
		</tr>
		<tr>
			<td>Alpha-Stim AID Kit</td>
			<td>Electromedical Products International Inc.</td>
			<td>SKU: 500KIT</td>
			<td>A total of 50 devices ordered for research purposes. 
			From the site: &#34;A prescription or order from a licensed healthcare professional is required to purchase this device (within the USA). FDA cleared for anxiety, insomnia and pain only, with approval for depression outside of the United States.&#34;</td>
		</tr>
		<tr>
			<td>CONN Toolbox v21a16 (RRID:SCR_009550)&#160;</td>
			<td>Whitfield-Gabrieli and Nieto-Castanon</td>
			<td>Version v21a16 (RRID:SCR_009550)</td>
			<td>CONN is an open-source SPM-based cross-platform software for the computation, display, and analysis of functional connectivity Magnetic Resonance Imaging (fcMRI). CONN is used to analyze resting state data (rsfMRI) as well as task-related designs.&#160;</td>
		</tr>
		<tr>
			<td>DSI Studio&#160;(RRID:SCR_009557)&#160;</td>
			<td>Fang-Cheng (Frank) Yeh</td>
			<td>RRID:SCR_009557</td>
			<td>DSI Studio is a tractography software tool that maps brain connections and correlates findings with neuropsychological disorders. It is a collective implementation of several diffusion MRI methods, including diffusion tensor imaging (DTI), generalized q-sampling imaging (GQI), q-space diffeomorphic reconstruction (QSDR), diffusion MRI connectometry, and generalized deterministic fiber tracking.</td>
		</tr>
		<tr>
			<td>fMRIPrep 20.2.5 (RRID:SCR_016216)&#160;</td>
			<td>NiPreps (NeuroImaging PREProcessing tools)</td>
			<td>Version 20.2.5. (RRID:SCR_016216)</td>
			<td>A functional magnetic resonance imaging (fMRI) data preprocessing pipeline that is designed to provide an easily accessible, state-of-the-art interface that is robust to variations in scan acquisition protocols and that requires minimal user input, while providing easily interpretable and comprehensive error and output reporting. It performs basic processing steps (coregistration, normalization, unwarping, noise component extraction, segmentation, skull-stripping, etc.) providing outputs that can be easily submitted to a variety of group level analyses, including task-based or resting-state fMRI, graph theory measures, and surface or volume-based statistics.</td>
		</tr>
		<tr>
			<td>MRIQC&#160;</td>
			<td>NiPreps (NeuroImaging PREProcessing tools)</td>
			<td></td>
			<td>MRIQC extracts no-reference IQMs (image quality metrics) from structural (T1w and T2w) and functional MRI (magnetic resonance imaging) data. (not directly used for analyses)</td>
		</tr>
		<tr>
			<td>Sammons Preston Jamar Hydraulic Hand Dynamometer</td>
			<td>Alpha Med Inc.</td>
			<td>SKU SAMP5030J1</td>
			<td>From the website: Ideal for routine screening of grip strength and initial and ongoing evaluation of clients with hand trauma and dysfunction. 
			Unit comes with carrying/storage case, certificate of calibration and complete instructions. Warranted for one full year. The warranty does not cover calibration. Latex free.</td>
		</tr>
		<tr>
			<td>SPRI 5-Pound Vinyl-Coated Weight</td>
			<td>SPRI | Amazon</td>
			<td>N/A</td>
			<td>Color: (E) Dark Blue | 5-Pound. Appears on Amazon: Dumbbells Hand Weights Set of 2 - Vinyl Coated Exercise &#38; Fitness Dumbbell for Home Gym Equipment Workouts Strength Training Free Weights for Women, Men (1-10 Pound, 12, 15, 18, 20 lb), https://www.amazon.com/stores/SPRI/Weights/page/9D10835A-CFAB-4DA1-BEE9-AE993C6B5BC1</td>
		</tr>
		<tr>
			<td>SPRI 8-Pound Vinyl-Coated Weight</td>
			<td>SPRI | Amazon</td>
			<td>N/A</td>
			<td>Color: (H) Black |8-Pound. Appears on Amazon: Dumbbells Hand Weights Set of 2 - Vinyl Coated Exercise &#38; Fitness Dumbbell for Home Gym Equipment Workouts Strength Training Free Weights for Women, Men (1-10 Pound, 12, 15, 18, 20 lb), https://www.amazon.com/stores/SPRI/Weights/page/9D10835A-CFAB-4DA1-BEE9-AE993C6B5BC1</td>
		</tr>
	</tbody>
</table>

a randomized, sham-controlled trial of cranial electrical stimulation for fibromyalgia pain and physical function, using brain imaging biomarkers

纤维肌痛是一种慢性疼痛综合征，表现为一系列广泛的症状，包括身体机能下降、疲劳、认知障碍和其他躯体症状。现有的疗法通常不足以治疗症状，疼痛控制不足通常会导致使用阿片类药物进行尝试管理。颅脑电刺激 （CES） 是一种很有前途的非药物治疗疼痛疾病的选择，它使用脉冲电流刺激通过经皮电极改变大脑功能。这些神经机制以及CES在纤维肌痛症状缓解中的应用需要进一步探索。
来自亚特兰大退伍军人事务医疗保健系统 （VAHCS） 的总共 50 名被诊断患有纤维肌痛的参与者被招募，然后被随机分配到安慰剂加标准治疗组或积极的 CES 加标准治疗组。基线评估是在治疗开始前获得的。两种干预措施都发生在12周内，受试者在治疗开始后6周和12周接受评估。主要结局调查了应用CES是否会发生疼痛和功能改善。此外，在 6 周和 12 周的时间点获得基线和随访静息态功能连接磁共振成像 （rs-fcMRI），以评估神经连接生物标志物的临床应用以及与治疗效果相关的潜在神经关联。
这是一项随机、安慰剂对照试验，旨在确定 CES 改善纤维肌痛疼痛和功能的疗效，并进一步开发 rs-fcMRI 作为评估慢性疼痛和镇痛反应的神经相关性和机制的临床工具。

Of the many existing states of chronic pain, one of the most notoriously difficult diseases to diagnose, clinically assess, and treat is fibromyalgia. Fibromyalgia is a debilitating chronic pain syndrome that involves chronic widespread pain, decreased physical function, fatigue, psycho-emotional and sleep disturbances, and various somatic complaints affecting approximately 2-3% of the general population in the Americas (about 8 million people in the U.S.)1. Diagnosis of the disease is heavily reliant on a patient&#39;s understanding of their own symptom profile and pain experience, and without that proper understanding by both clinician and patient of the disease, methods of treatment lose considerable efficacy2. A better definition of fibromyalgia&#39;s origins and impact as well as a reliable clinical biomarker to guide fibromyalgia diagnosis and treatment&#160;are necessary to best serve all patients.
Even with a confirmed diagnosis, difficulties with the treatment process only grow. As a whole, chronic pain affects more individuals than heart disease, diabetes, and cancer combined. The subjective nature of its assessment places it as a primary driver for the opioid epidemic, especially given the difficulty in discerning incompletely treated physical pain from substance use disorder and drug-seeking behavior3. In 2020, 91,799 drug overdose deaths occurred in the United States (a 30% increase from 2019), and opioids were found to be the main cause of these deaths (74.8% of all 2020 drug overdose deaths)4. Thus, non-pharmacologic alternatives are needed for chronic pain and fibromyalgia treatment to slow the opioid epidemic, which is particularly important in the veteran population where the risk of suicide and opioid use disorder is higher5. Non-pharmacologic and complementary therapies are therefore often used as first-line treatments6.
The search for novel, efficacious fibromyalgia interventions has led many researchers and clinicians to methods of noninvasive brain stimulation, including cranial stimulation. Even though the pathophysiologic mechanisms that result in the development of the disease have not been definitively determined, existing evidence supports the idea that fibromyalgia is a disorder of autonomic nervous system dysfunction and central (i.e., brain and spinal cord) pain processing mechanisms7,8. Stimulation of certain areas of the brain could lead to improved function in those areas of processing. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) have been correlated with reductions in pain but have also been associated with activation site scalp irritation, headaches, and inaccessibility outside of treatment facilities9. Noninvasive vagus nerve stimulation (nVNS), which can provide neuromodulation through stimulation over the skin at the neck or at the level of the ear, has the potential for the treatment of chronic pain, and invasive vagus nerve stimulation (VNS) has been shown to improve chronic pain symptoms10. However, neither invasive nor noninvasive VNS have been sufficiently explored in the literature or fully validated for use in fibromyalgia treatment11,12,13,14.
Cranial electrical stimulation (CES) is a non-pharmacological, noninvasive brain stimulation treatment that consists of pulsed, alternating microcurrent (less than 0.5 mA) applied via transcutaneous electrodes placed on the earlobes15. It is remarkably accessible and can be delivered through portable devices used by patients within their own living spaces. In comparison to other cranial stimulation methods, the noninvasive nature and the convenience of patient self-application at home increases the potential of CES as a beneficial option for widespread fibromyalgia treatment use and self-management of pain. It has been cleared by the U.S. Food and Drug Administration (FDA) as a treatment for insomnia, depression, anxiety, and pain15.
The current study evaluates the efficacy of CES as a fibromyalgia treatment modality by comparing active CES (administered by a true study device) versus sham CES (administered by a sham study device). There is some preliminary evidence to support the use of CES in the treatment of pain conditions such as fibromyalgia16,17. A 2001 study of 60 participants randomized to active or sham CES for 3 weeks of daily 60 min sessions revealed a 28% improvement in tender point scores, 27% improvement in general pain scores, and no placebo effect18. CES has not been evaluated in a veteran population, nor has it been adequately evaluated in males with fibromyalgia. A Veterans Affairs (VA)-funded systematic review of CES published in 2018 concluded that evidence is insufficient for CES to have clinically important effects on fibromyalgia, given that most trials had small sample sizes, short durations, and a high risk of bias due to inadequate blinding. However, the review suggests that CES does not cause serious side effects, and there is low-strength evidence to suggest modest benefits in patients with anxiety and depression19. Therefore, further research is warranted regarding the use of this FDA-cleared, low-risk device, particularly in fibromyalgia.
In order to fully evaluate the efficacy, researchers assessed physical fitness alongside neural biomarkers and pain experience. The purpose of treating chronic pain states is to improve physical function. Fibromyalgia is consistently correlated with negative effects on both physical function and patients&#39; perception of their own physical abilities20. Previous studies have utilized simple physical fitness assessments to determine stamina and mobility, such as the 6 Minute Walk Test (6MWT)20,21, Five Time Sit to Stand (5TSTS)20, and various measures of carrying capacity and strength in the context of daily activities22. To account for standard measures while also mitigating the amount of strenuous activity required right before an MRI scan, the study team used the 30-Second Chair Sit Stand Test as a measure of stamina and mobility and both bicep curls and a hand grip test as measures of strength23. The movements required in each of these assessments are very common in everyday activities, so it is a clear measure of how people are physically functioning in their day-to-day lives, both with and without treatment.
Even with subjective pain assessments and physical function measures of efficacy, the mechanisms of CES are not fully understood. Prior neuroimaging studies have sought a better understanding by exploring the direct effect of CES on network connectivity in the brain. Feusner et al.24 found that CES is associated with cortical deactivation for 0.5 Hz and 100 &#181;A stimulation of bilateral frontal, parietal, and posterior midline regions and postulated that frequency of stimulation may have more of an effect than current intensity in relation to cortical deactivation. Their group found significant effects on some but not all nodes of the default mode network (DMN). The authors suggest that based on this data, CES may affect resting state functional connectivity. Fibromyalgia and other chronic pain states have been shown to affect intrinsic brain connectivity in regions associated with pain and perception25,26, so treatments that alter functional connectivity in response could prove to be both beneficial and effective. Further exploration of the longer-term effects of daily treatment in relation to clinical improvement, as well as how deceased activation in the brain relates to previously observed decreases in electroencephalogram frequencies, is needed to further understand the therapeutic mechanism of action27.
Resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) is the neuroimaging method that allows for the observation of these functional connectivity changes. Longitudinal resting state fMRI allows clinicians and researchers to establish a baseline of resting state connectivity and track alterations over time in response to CES treatment methods. It also helps to determine how changes in functional connectivity are correlated to differences in the experience of pain. Initial studies of neuroimaging for fibromyalgia used positron emission tomography (PET) and single-photon-emission computed tomography (SPECT) to examine the brain, but there are issues with both techniques in this regard: SPECT has a lower resolution than PET, and PET scans are invasive, which is not preferable for patients experiencing chronic pain. Functional magnetic resonance imaging (fMRI) scans have greater resolution than SPECT, but they examine brain activity in response to patients&#39; specific actions or perceptions of stimuli28. It is rs-fcMRI scans that can outline functional connectivity between regions of the brain and may be able to determine where and how fibromyalgia exists as well as the best methods of treatment28.
Evaluating the efficacy of non-pharmacologic treatments for pain conditions such as fibromyalgia is of utmost importance both in the current setting of the opioid epidemic and in examining chronic pain as a risk factor for suicide29,30, which is substantially increased among the veteran population. Additionally, the lack of adequate clinical biomarkers for pain is a recognized knowledge gap. Using a combination of behavioral measures and neuroimaging at multiple timepoints to assess treatment response is a novel approach to fibromyalgia evaluation, as is the utilization of auricular CES as a treatment.
The protocol aims to address the gap in fibromyalgia research by investigating the effects of CES on pain and physical function outcomes and evaluating neuroimaging as a tool for predictive and response biomarkers related to the clinical outcomes of CES therapy31.

作者聚焦：慢性疼痛管理研究的方法和进展

一项使用脑成像生物标志物进行颅脑电刺激治疗纤维肌痛疼痛和身体功能的随机、假对照试验

We are trying to address two main issues with regards to pain research. The first is the need for non-invasive, non-pharmacologic therapies that can be effectively administered to individuals suffering from chronic pain. The second is the development of reliable biomarkers, such as the neuroimaging that we're using for the purposes of assessing both fibromyalgia pain and treatment response.The development and access of multiple open source neuro software packages allows for the streamlined use of neuroimaging data analysis. Many of these tools such as fMRIPrep allow researchers who are not familiar with the neuroimaging practices to complete critical pre-processing steps. To maintain blinding, we're unable to titrate for effect using the device as we would in a clinical setting.The stimulation is typically below the perceptual threshold, but we may be underdosing individuals in our study's treatment group, which causes a smaller effect size and difference between the groups. Cranial electrical stimulation is non-invasive. It's low risk, and it's accessible enough to be self-administered by participants in their own home settings.We can also extract usage rates from each of the research devices to properly evaluate compliance with the treatment. And resting state functional connectivity MRI allows us to assess changes in the brain that may occur as a result of our treatment. We anticipate that our research will further guide biomarker development using neuroimaging as a tool.This contributes to a better understanding of the neural basis of pain, and our hope is that these techniques will eventually be used to guide clinical diagnosis and decision making for individuals suffering from pain.

在招聘结果方面，参与者主要是根据亚特兰大退伍军人事务部医疗保健系统的概述规定通过邮寄招聘信函和后续电话招募的。研究小组共招募了 50 名参与者，证明了所用方法在实现招募目标方面的有效性（见 图 2）。使用新的临床纤维肌痛诊断标准使研究小组能够正确筛选出不符合纤维肌痛标准的个体32。向可能的参与者询问纤维?...

Read this Scientific Article Protocol about Author Spotlight: Towards Biomarker Development Using Neuroimaging as a Tool to Enhance the Understanding of the Neural Basis of Pain at JoVE.com

目前的研究是一项随机、安慰剂对照试验，旨在确定颅脑电刺激 （CES） 改善纤维肌痛疼痛和功能的疗效，并进一步开发静息功能连接磁共振成像 （rs-fcMRI） 作为评估慢性疼痛和镇痛反应的神经相关性和机制的临床工具。

Fibromyalgia is a chronic pain syndrome that presents with a constellation of broad symptoms, including decreased physical function, fatigue, cognitive ...

我们正在努力解决与疼痛研究有关的两个主要问题。首先是需要非侵入性、非药物疗法，这些疗法可以有效地用于患有慢性疼痛的个体。第二个是可靠的生物标志物的开发，例如我们用于评估纤维肌痛疼痛和治疗反应的神经影像学。多个开源神经软件包的开发和访问允许简化神经影像数据分析的使用。其中许多工具（例如fMRIPrep）使不熟悉神经影像学实践的研究人员能够完成关键的预处理步骤。为了保持盲法，我们无法像在临床环境中那样使用该设备滴定效果。刺激通常低于知觉阈值，但我们可能在研究的治疗组中对个体剂量不足，这会导致组间效应量和差异较小。颅脑电刺激是非侵入性的。它是低风险的，而且它足够容易获得，可以由参与者在他们自己的家庭环境中自我管理。我们还可以从每个研究设备中提取使用率，以正确评估对治疗的依从性。静息态功能连接MRI使我们能够评估由于我们的治疗而可能发生的大脑变化。我们预计，我们的研究将使用神经影像学作为工具进一步指导生物标志物的开发。这有助于更好地理解疼痛的神经基础，我们希望这些技术最终将用于指导患有疼痛的个体的临床诊断和决策。

a-randomized-sham-controlled-trial-cranial-electrical-stimulation-for

Research

JoVE Journal

Medicine

A Randomized, Sham-Controlled Trial of Cranial Electrical Stimulation for Fibromyalgia Pain and Physical Function, Using Brain Imaging Biomarkers

Fibromyalgia is a chronic pain syndrome that presents with a constellation of broad symptoms, including decreased physical function, fatigue, cognitive disturbances, and other somatic complaints. Available therapies are often insufficient in treating symptoms, with inadequate pain control commonly leading to opioid usage for attempted management. Cranial electrical stimulation (CES) is a promising non-pharmacologic treatment option for pain conditions that uses pulsed electrical current stimulation to modify&#160;brain function via transcutaneous electrodes. These neural mechanisms and the applications of CES in fibromyalgia symptom relief require further exploration.
A total of 50 participants from the Atlanta Veterans Affairs Healthcare System (VAHCS) diagnosed with fibromyalgia were enrolled and then block-randomized into either a placebo plus standard therapy or active CES plus standard therapy group. Baseline assessments were obtained prior to the start of treatment. Both interventions occurred over 12 weeks, and participants were assessed at 6 weeks and 12 weeks after treatment initiation. The primary outcome investigated whether pain and functional improvements occur with the application of CES. Additionally, baseline and follow-up resting state functional connectivity magnetic resonance imaging (rs-fcMRI) were obtained at the 6-week and 12-week time points to assess for clinical applications of neural connectivity biomarkers and the underlying neural associations related to treatment effects.
This is a randomized, placebo-controlled trial to determine the efficacy of CES for improving pain and function in fibromyalgia and further develop rs-fcMRI as a clinical tool to assess the neural correlates and mechanisms of chronic pain and analgesic response.

The current study is a randomized, placebo-controlled trial to determine the efficacy of cranial electrical stimulation (CES) for improving pain and function in fibromyalgia and further develop resting functional connectivity magnetic resonance imaging (rs-fcMRI) as a clinical tool to assess the neural correlates and mechanisms of chronic pain and analgesic response.