Department of Orthopaedic Surgery, Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, United States.
Department of Physical Therapy, University of Florida, Gainesville, FL, United States.
Pain. 2023 Feb 1;164(2):305-315. doi: 10.1097/j.pain.0000000000002700. Epub 2022 May 23.
Prior cohort studies validated that a subgroup defined by a specific COMT genotype and pain catastrophizing is at increased risk for heightened responses to exercise-induced or surgically induced shoulder pain. In this clinical trial, we used our preclinical model of exercise-induced muscle injury and pain to test the efficacy of interventions matched to characteristics of this high-risk subgroup (ie, personalized medicine approach). Potential participants provided informed consent to be screened for eligibility based on subgroup membership and then, as appropriate, were enrolled into the trial. Participants (n = 261) were randomized to 1 of 4 intervention groups comprised of pharmaceutical (propranolol or placebo) and informational (general education or psychologic intervention) combinations. After muscle injury was induced, participants received randomly assigned treatment and were followed for the primary outcome of shoulder pain intensity recovery over 4 consecutive days. Recovery rates were 56.4% (placebo and psychologic intervention), 55.4% (placebo and general education), 62.9% (propranolol and psychologic intervention), and 56.1% (propranolol and general education). No statistical differences were found between intervention groups in the primary analyses. Additional analyses found no differences between these intervention groups when shoulder pain duration was an outcome, and no differential treatment responses were detected based on sex, race, or level of pain catastrophizing. This trial indicates that these treatments were not efficacious for this high-risk subgroup when shoulder pain was induced by exercise-induced muscle injury. Accordingly, this phenotype should only be used for prognostic purposes until additional trials are completed in clinical populations.
先前的队列研究已经验证，特定 COMT 基因型和疼痛灾难化的亚组患者在对运动引起或手术引起的肩部疼痛的反应中风险增加。在这项临床试验中，我们使用运动引起的肌肉损伤和疼痛的临床前模型来测试针对该高风险亚组特征的干预措施的疗效（即，个性化医疗方法）。潜在参与者提供了知情同意书，以根据亚组成员资格进行筛选，然后酌情纳入试验。参与者（n = 261）被随机分配到 4 个干预组中的 1 个，这些干预组由药物（普萘洛尔或安慰剂）和信息（一般教育或心理干预）组合组成。在肌肉损伤诱导后，参与者接受随机分配的治疗，并在 4 天内连续评估肩部疼痛强度恢复的主要结局。恢复率为 56.4%（安慰剂和心理干预）、55.4%（安慰剂和一般教育）、62.9%（普萘洛尔和心理干预）和 56.1%（普萘洛尔和一般教育）。在主要分析中，干预组之间未发现统计学差异。进一步分析发现，当肩部疼痛持续时间作为结果时，这些干预组之间没有差异，并且根据性别、种族或疼痛灾难化程度没有检测到差异的治疗反应。这项试验表明，当肩部疼痛由运动引起的肌肉损伤引起时，这些治疗方法对这个高风险亚组没有疗效。因此，在完成临床试验人群中的额外试验之前，该表型仅应用于预后目的。
