Genetic Predictors of Acute and Chronic Musculoskeletal Pain After Minor MVC

描述(申请人提供)：每年有500多万人在美国急诊科(EDs)接受治疗，在发生轻微的机动车碰撞(MVC)后出院。持续性疼痛(最常见的颈部疼痛)发生在这些人中的10%-20%，仅在美国每年就造成290亿美元的经济影响。关于这些常见和昂贵疾病的发病机制的当代知识在MVC后疼痛发病的生物心理社会模型中进行了总结。近年来，对心理因素促进持续性疼痛发展的机制的识别和详细描述极大地改进了生物心理社会模型。相比之下，生物心理社会模型中的生物因素仍然相对模糊，通常仅限于对坠机严重程度或初始伤害的估计。有趣的是，越来越多的证据表明，影响肾上腺素能系统功能的遗传特征可能构成创伤后疼痛发生的重要生物易损性因素，因此纳入生物心理社会模型可能是重要的。即时和持续的肾上腺素能反应受到肾上腺素能系统重要组成部分功能的影响，包括调节突触儿茶酚胺水平的酶和转运体，以及协调细胞反应的受体。越来越多的文献记录了这些成分影响疼痛处理的能力，研究人员的试点数据支持这样的假设，即这些成分的遗传变异会影响在轻微MVC后发生即时和持续性肌肉骨骼疼痛的易感性。这项拟议的研究名为轻微MVC后急性和慢性肌肉骨骼疼痛的遗传预测因素，其目的是评估决定与疼痛感知相关的特定肾上腺素系统过程的基因类型，当结合与碰撞相关的、心理和其他因素时，是否会改善对轻微MVC后立即和持续性颈部疼痛症状的预测。795名在轻微MVC后提出接受评估的患者将被招募到急诊科，并将接受初步的ED评估，包括采集血液进行基因分析。然后，患者将在MVC后1、6和12个月接受采访，以评估疼痛结果。试点数据证明了研究团队执行拟议研究的能力，并支持选定的肾上腺素能系统相关遗传因素的潜在预测价值。这项拟议的研究提供了一个前所未有的机会来开发丰富的生物心理社会预测模型，该模型综合了多个领域的因素，可以预测MVC后持续性颈部疼痛。这些模型将提供关于个体脆弱性特征以及在MVC后疼痛的发展过程中遗传和非遗传因素之间的相互作用的重要新知识。公共卫生相关性拟议的研究将提供关于创伤后持续性肌肉骨骼疼痛发生过程中的个体脆弱性特征以及遗传和非遗传因素之间相互作用的新知识。了解肌肉骨骼疼痛疾病的病因学对公众的健康很重要，因为这些疾病很常见，会引起巨大的疼痛和痛苦，并给社会带来非常昂贵的代价。

DESCRIPTION (provided by applicant): Each year, more than 5 million people are treated in US Emergency Departments (EDs) after "minor" motor vehicle collision (MVC) and discharged to home. Persistent pain (most commonly neck pain) develops in 10- 20% of these individuals, with an economic impact of $29 billion per year in the United States alone. Contemporary knowledge regarding the pathogenesis of these common and costly disorders is summarized in biopsychosocial models of post-MVC pain pathogenesis. In recent years, the identification and detailed delineation of mechanisms by which psychological factors contribute to persistent pain development has substantially improved the biopsychosocial model. In contrast, biological factors in the biopsychosocial model remain relatively poorly defined, and are generally limited to estimates of crash severity or initial injury only. Interestingly, increasing evidence indicates that genetic characteristics influencing adrenergic system function may constitute important biological vulnerability factors for the development of posttraumatic pain, and thus may be important to incorporate into the biopsychosocial model. The immediate and ongoing adrenergic response is influenced by the function of important adrenergic system components, including enzymes and transporters that modulate synaptic catecholamine levels and receptors that orchestrate the cellular response. A growing literature documents the ability of these components to influence pain processing, and the investigators' pilot data support the hypothesis that genetic variation in these components affects vulnerability to develop immediate and persistent musculoskeletal pain after minor MVC. The goal of the proposed research, Genetic predictors of acute and chronic musculoskeletal pain after minor MVC, is to assess whether genotypes determining specific adrenergic system processes relevant to pain perception will, when combined with crash-related, psychological, and other factors, improve the prediction of immediate and persistent neck pain symptoms after minor MVC. Patients presenting for evaluation after minor MVC (n = 795) will be recruited in the ED and will receive initial ED evaluation including blood collection for genetic analyses. Patients will then be interviewed 1, 6, and 12 months after the MVC to assess pain outcomes. Pilot data demonstrate the ability of the study team to perform the proposed study and support the potential predictive value of the selected adrenergic system-related genetic factors. The proposed study provides an unprecedented opportunity to develop rich biopsychosocial prediction models of persistent post-MVC neck pain which integrate factors across multiple domains. These models will provide important new knowledge regarding both individual vulnerability characteristics and interactions between genetic and non-genetic factors during the development of post-MVC pain. PUBLIC HEALTH RELEVANCE The proposed study will provide new knowledge regarding both individual vulnerability characteristics and interactions between genetic and non-genetic factors during the development of persistent posttraumatic musculoskeletal pain. Understanding the etiology of musculoskeletal pain disorders is important to the public's health because these disorders are common, cause significant pain and suffering, and are very costly to society.