Exploring the biomarkers for new-onset chronic pain in long covid. A mechanistic study

探索长期新冠慢性疼痛的生物标志物。

• 批准号: 2717703
• 金额: --
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2717703
• 关键词: Exploring; biomarkers; new; onset; chronic

An estimated 1.8 million people in UK private households suffer from Long COVID (LC), which refers to the signs and symptoms that persist beyond 4 weeks from the acute phase of COVID-19 infection and cannot be explained by an alternative diagnosis. Research shows that pain is among the most common post-COVID symptoms, with epidemiological studies suggesting a prevalence of up to 71% in LC patients. LC-chronic pain refers to new-onset pain of musculoskeletal or neuropathic origin that arises following acute infection and remains for longer than 3 months. Only few studies have reported the prevalence of pain symptoms at 3 or more months post-infection, compatible with the criteria for chronic pain . Chronic pain is known to have a significant negative impact on individual health-related quality of life and functional status. The rapidly increasing number of LC cases and associated pain complaints is likely to further contribute to the individual and societal burden of chronic pain. There is an urgent unmet need to investigate underlying pathophysiological mechanisms of LC-chronic pain and potential interventions to alleviate pain-related outcomes in LC patients. Evidence on the pathological processes underlying the development and maintenance of LC-chronic pain is lacking. A mechanism known to contribute to pain chronification is amplification of neural processing associated with perception of pain within the central nervous system (referred to as central sensitisation), resulting from maladaptive structural and functional changes in central nociceptive pathways (15). This has been shown to contribute to a variety of chronic pain conditions and is likely to also play a role in LC-chronic pain. Several authors have identified potential neurophysiological signatures of pain hypersensitivity in chronic pain patients using electroencephalography (EEG). One strong candidate EEG marker of chronic pain is abnormal alpha activity with chronic pain patients showing lower resting-state alpha activity compared to controls. Identification of EEG markers of disease opens a promising avenue for research on the therapeutic applicability of targeted non-invasive neuromodulation techniques for the management of pain. One such technique is neurofeedback that entails training to self-regulate one's own neural oscillatory activity, whereby sensory representation of cortical activity is fed back to the individual in real-time. Several studies have reported promising analgesic effects of enhancing alpha power via neurofeedback training or entrainment by external rhythmic stimulation.The contribution of maladaptive plasticity of central nervous system to pain chronification has not yet been studied in LC. Assessing the presence of EEG markers of chronic pain in LC may help to elucidate underlying pathological processes as well as to identify promising targets of non-invasive personalised therapeutic interventions. The proposed study consists of: Work Package WP1: a longitudinal cross-sectional online study using questionnaires to assess pain (severity, location, other characteristics), functioning, psychological variables, demographics and quality of life over a 2-year follow-up period. Work Package WP2: a case-control study for in-depth EEG analysis of spectral power of different waveforms and event related potentials in LC patients with new-onset chronic pain compared to those without. The association between pain-related outcomes assessed by self-reported questionnaires and EEG markers will be investigated. If EEG markers of LC-chronic pain are identified, an interventional study will be undertaken to explore the potential beneficial effects of a targeted-neurofeedback training in a sample of patients. The outcomes of this study may be clinically relevant for LC patients and those suffering from primary chronic pain conditions.

据估计，英国私人家庭中有180万人患有长期COVID（LC），这是指COVID-19感染急性期后持续超过4周的体征和症状，并且无法通过替代诊断来解释。研究表明，疼痛是COVID后最常见的症状之一，流行病学研究表明LC患者的患病率高达71%。LC-慢性疼痛是指急性感染后出现的肌肉骨骼或神经源性新发疼痛，持续时间超过3个月。只有少数研究报告了感染后3个月或3个月以上疼痛症状的患病率，符合慢性疼痛的标准。已知慢性疼痛对个体健康相关的生活质量和功能状态具有显著的负面影响。LC病例和相关疼痛主诉数量的迅速增加可能会进一步加重慢性疼痛的个人和社会负担。目前迫切需要研究LC慢性疼痛的潜在病理生理机制和潜在的干预措施，以减轻LC患者的疼痛相关结局。缺乏LC慢性疼痛发展和维持的病理过程的证据。已知有助于疼痛慢性化的机制是与中枢神经系统内疼痛感知相关的神经处理放大（称为中枢敏化），这是由中枢伤害性通路中的适应不良结构和功能变化引起的（15）。这已被证明有助于各种慢性疼痛状况，并可能在LC慢性疼痛中发挥作用。几位作者已经使用脑电图（EEG）确定了慢性疼痛患者疼痛超敏反应的潜在神经生理学特征。慢性疼痛的一个强有力的候选EEG标记物是异常α活动，与对照相比，慢性疼痛患者显示出较低的静息状态α活动。疾病的EEG标记物的识别为研究用于疼痛管理的靶向非侵入性神经调节技术的治疗适用性开辟了一条有希望的途径。一种这样的技术是神经反馈，其需要训练以自我调节自己的神经振荡活动，从而将皮质活动的感觉表征实时反馈给个体。一些研究报道了通过神经反馈训练或外部节律性刺激提高α功率的有希望的镇痛作用，但中枢神经系统的适应不良可塑性对LC疼痛慢性化的贡献尚未研究。评估LC中慢性疼痛的EEG标记物的存在可能有助于阐明潜在的病理过程，以及确定有前途的非侵入性个性化治疗干预的目标。拟议的研究包括：工作包WP 1：一项纵向横断面在线研究，使用问卷评估疼痛（严重程度、位置、其他特征）、功能、心理变量、人口统计学和2年随访期内的生活质量。工作包WP 2：一项病例对照研究，对伴有新发慢性疼痛的LC患者与不伴有新发慢性疼痛的LC患者进行不同波形和事件相关电位频谱功率的深入EEG分析。将研究通过自我报告问卷评估的疼痛相关结局与EEG标志物之间的相关性。如果确定了LC慢性疼痛的EEG标志物，将进行干预性研究，以探索患者样本中靶向神经反馈训练的潜在有益影响。本研究的结果可能与LC患者和患有原发性慢性疼痛疾病的患者临床相关。