Individual Differences in Pain Modulation as Predictors of Post-Surgical Pain

描述（由申请人提供）：疼痛是乳腺癌管理中的一个关键问题，但认识不足，治疗不足。最近的研究估计，大约50%接受乳房肿瘤切除术的女性会经历持续性疼痛，这与生活质量受损、严重残疾以及在一些研究中与癌症相关的死亡率有关。到目前为止，对接受乳房手术的女性的研究已经确定了一些一致或强有力的预测谁报告长期治疗相关疼痛，以及到什么程度。虽然以前没有在乳腺癌治疗的背景下进行过研究，但新出现的证据表明，中枢神经系统如何处理疼痛的个体差异可能是手术后疼痛程度的重要因素。拟议的项目是一项前瞻性队列研究的妇女接受肿块切除术后，放射治疗的早期乳腺癌的治疗。术前将通过评估对简短、标准化刺激（即热、冷、压力）的反应来评价疼痛反应。在急性恢复期，将使用电子日记和自动电话随访相结合的方式对患者进行随访，以评估治疗相关疼痛、镇痛剂使用情况和疼痛相关后遗症。这项研究将确定：（1）术前心理物理测试评估疼痛反应是否有助于预测乳房肿瘤切除术后的急性和长期疼痛结局，（2）在预测治疗相关疼痛结局方面，什么是实验性疼痛反应的最有效措施。我们假设，表现出最大程度的疼痛敏感性和最低程度的内源性疼痛抑制的个体将报告最急性的疼痛，需要最多的镇痛药，并报告最高水平的长期疼痛和疼痛相关的残疾。这项工作将提供有关乳腺癌治疗后疼痛的机制和风险因素的重要信息。此外，这些发现可能会增强未来的疼痛治疗研究，使研究人员能够针对镇痛药临床试验的高风险个体。最后，这项研究的结果将对术后疼痛管理产生普遍影响;那些表现出最高风险的人可能会受益于额外的先发制人或术后镇痛干预，或更长时间的更密集随访。

DESCRIPTION (provided by applicant): Pain is a critical yet poorly-understood and under-treated problem in the management of breast cancer. Recent studies have estimated that approximately 50% of women who undergo lumpectomies will experience persistent pain, which is associated with impaired quality of life, significant disability, and, in some studies, cancer-related mortality. To date, studies of women undergoing breast surgery have identified few consistent or strong predictors of who reports long-term treatment-related pain, and to what degree. Though not previously studied in the context of breast cancer treatment, emerging evidence suggests that individual differences in how the central nervous system processes pain may be a powerful contributor to the extent of pain experienced after surgery. The proposed project is a prospective cohort study of women undergoing lumpectomy followed by radiation therapy for treatment of early-stage breast cancer. Pain responses will be evaluated pre-surgically by assessing responses to brief, standardized stimuli (i.e, heat, cold, pressure). Patients will be followed during their acute recovery periods using a combination of electronic diaries and automated telephone calls to assess treatment-related pain, analgesic usage, and pain-related sequelae. This study will determine: (1) whether pre-operative psychophysical testing to evaluate pain responses is useful in predicting acute and longer-term pain outcomes after lumpectomy, and (2) what are the most effective measures of experimental pain responses in predicting treatment-related pain outcomes. We hypothesize that the individuals who show the greatest degree of pain sensitivity and the lowest degree of endogenous pain inhibition will report the most acute pain, require the most analgesics, and report the highest levels of long-term pain and pain-related disability. This work will provide important information on mechanisms and risk factors contributing to the experience of pain following treatment for breast cancer. In addition, the findings may enhance future pain-treatment studies by allowing investigators to target high-risk individuals for clinical trials of analgesics. Finally, results from this research would have general implications for post-surgical pain management; those who showed the most high-risk profiles might benefit from additional pre-emptive or post-operative analgesic interventions, or more intense follow-up for a longer period.