Variation in Home Opioid Consumption after Total Knee Replacement: Investigating the Role of Pain Sensitivity and Gene Expression

摘要 类似手术后阿片类药物的使用存在较大差异，有些患者使用较少的阿片类药物 其他人消费阿片类药物的时间远远超过预期的急性疼痛发作。长期使用阿片类药物被认为是 最常见的手术并发症之一。最新发展的预测术后变异性的模型 阿片类药物的使用主要集中在临床和心理调查数据上，但留下了相当大比例的 变异性无法解释。由于目前尚不清楚长期使用阿片类药物是由于长期疼痛还是其他原因 因素，这个项目建议通过前瞻性地检查重要的疼痛来扩展先前的研究 疼痛的敏感性和生物标志物预测指标，以确定其对阿片类药物使用的影响。疼痛是一种生物心理社会 因此，这些重要的生物变量的加入将导致机械性的增加 了解术后阿片类药物消耗的可变性，从而更好地管理术后 通过提供潜在的新治疗靶点来缓解疼痛。一个这样未被研究的变量是个人的 潜在的疼痛敏感性，可通过定量感觉测试(QST)衡量。QST在住院病人预测中的应用 阿片类药物的使用和疼痛导致了不一致的发现，但最近的研究强调了QST在 预测术后家庭阿片类药物的使用。长期以来，人们的猜测都集中在遗传因素上。 疼痛敏感性和阿片类药物使用的变异性。候选基因和全基因组研究已经证明 不能充分研究疼痛的复杂特征，导致效果规模较小，缺乏重复性。 评估基因表达是一种可用于加强对术后疼痛的研究的方法。 血液中的基因表达分析已经确定了导致从 急性到慢性下腰痛，支持了这样一种假设，即从 术前到术后早期和晚期的时间段可以确定过渡到 术后疼痛时间延长。通过整合遗传和基因表达数据，我们将评估急性 手术疼痛在血液中留下特征，可以通过基因表达来识别，这可能会影响 术后疼痛敏感性和随后的阿片类药物使用。我们的建议集中在全膝关节置换术上 (TKA)人群，因为该人群表现出术后疼痛和 阿片类药物的使用，预计在不久的将来将增加700%。该项目提出了创新性的 将标准的人口统计学、临床和心理学变量与新的神经生理学、遗传学、 和基因表达数据，以全面检查术后疼痛和最终阿片类药物使用的可变性 通过生物心理社会镜头。

Abstract Great variation exists in opioid consumption after similar surgeries, with some patients using few opioids while others consume opioids well beyond the expected acute pain episode. Prolonged opioid use is considered one of the most common surgical complications. Recent models developed to predict the variability in postoperative opioid use focus primarily on clinical and psychological survey data, but leave a significant proportion of the variability unexplained. As it is unclear whether prolonged opioid use results from prolonged pain or other factors, this project proposes to extend the previous research by prospectively examining important pain sensitivity and biomarker predictors of pain to determine their effect on opioid use. Pain is a biopsychosocial phenomenon, so the inclusion of these important biological variables will lead to increased mechanistic understanding of postoperative opioid consumption variability and enable better management of postoperative pain by providing potential new therapeutic targets. One such understudied variable is an individual’s underlying pain sensitivity, measurable by quantitative sensory testing (QST). Use of QST to predict inpatient opioid use and pain has led to inconsistent findings, but recent studies highlight a promising role for QST to predict postoperative home opioid use. Speculation has long focused on genetic influences as a factor in variability in pain sensitivity and opioid use. Candidate gene and whole genome-wide studies have proven to be inadequate to study the complex trait of pain, resulting in small effect sizes and lack of reproducibility. Assessing gene expression is an approach that can be used to augment the research on postoperative pain. Gene expression analyses in blood have identified changes that confer vulnerability for the transition from acute to chronic low back pain, lending support to the hypothesis that changes in gene expression from preoperative to early and later postoperative time periods may identify early markers for the transition to prolonged postoperative pain. By integrating genetic and gene expression data, we will assess whether acute surgical pain leaves signatures in the blood that can be identified through gene expression which can influence postoperative pain sensitivity and subsequent opioid use. Our proposal focuses on the total knee arthroplasty (TKA) population, as this population demonstrates one of the highest variabilities in postoperative pain and opioid use, and is projected to increase 700% within the near future. This project proposes to innovatively incorporate standard demographic, clinical, and psychological variables with novel neurophysiological, genetic, and gene expression data to holistically examine the variability in postoperative pain, and ultimately opioid use through the biopsychosocial lens.