Department of Medical Oncology, Dana-Farber Cancer Institute, and Harvard Medical School, 450 Brookline Ave, Boston, MA 02115, USA.
Integrative Medicine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 321 East 61st Street, New York, NY 10065, USA.
Biomed Pharmacother. 2024 Jun;175:116728. doi: 10.1016/j.biopha.2024.116728. Epub 2024 May 10.
Patients' expectations and beliefs regarding the potential benefits and harms of medical interventions may induce placebo and nocebo effects, and affect the response to pain therapies. In a randomized clinical trial, we examined the effect of placebo and nocebo expectations on pain relief and adverse events (AEs) in association with a topical treatment among 65 cancer survivors experiencing chronic musculoskeletal pain. Participants received either a 1% camphor-based topical pain patch or a placebo treatment for 14 days. We measured pain severity with the worst pain item of the Brief Pain Inventory (BPI) at baseline and 14 days and treatment expectations at baseline with validated expectation questionnaires. We found that high vs. low nocebo expectations decreased pain severity improvements by 2.5 points (95% confidence interval [CI] -3.8 to -1.2; p<0.001) on a 0-10 numeric rating scale of the BPI and pain response rate by 42.7% (95% CI 0.2-0.6; p<0.001) at day 14, irrespective of placebo expectation status or treatment arms. Patients with high vs. low nocebo expectations in the true arm reported 22.4% more unwanted AEs. High nocebo expectations were associated with increased AEs by 39.5% (odds ratio: 12.0, 95% CI 1.2, 145.5; p=0.029) and decreased pain response in the true arm vs. placebo. Our study demonstrated that nocebo expectations, rather than placebo expectations, elevate the risk of AEs and compromise the effect of topical pain interventions. The findings raise the possibility that nocebo expectations may worsen somatic symptoms through heightening central pain amplification and should be further investigated.
患者对医疗干预潜在益处和危害的期望和信念可能会引起安慰剂和反安慰剂效应，并影响疼痛治疗的反应。在一项随机临床试验中，我们研究了安慰剂和反安慰剂期望对 65 名患有慢性肌肉骨骼疼痛的癌症幸存者接受局部治疗时疼痛缓解和不良事件（AE）的影响。参与者接受 1%薄荷脑基局部止痛贴或安慰剂治疗 14 天。我们使用验证过的期望问卷在基线和第 14 天测量了 BPI 的最差疼痛项目来测量疼痛严重程度，并在基线时测量了治疗期望。我们发现，高反安慰剂期望比低反安慰剂期望使 BPI 的数字评分量表上的疼痛严重程度改善降低了 2.5 分（95%置信区间[CI] -3.8 至-1.2；p<0.001），在第 14 天的疼痛反应率降低了 42.7%（95%CI 0.2-0.6；p<0.001），而不管安慰剂期望状态或治疗臂如何。在真实臂中，高反安慰剂期望的患者报告的不良事件增加了 22.4%。高反安慰剂期望与不良事件增加 39.5%（比值比：12.0，95%CI 1.2，145.5；p=0.029）和真实臂与安慰剂相比疼痛反应降低有关。我们的研究表明，反安慰剂期望而不是安慰剂期望会增加不良事件的风险，并影响局部疼痛干预的效果。这些发现提出了一种可能性，即反安慰剂期望可能通过增强中枢疼痛放大而使躯体症状恶化，应进一步研究。
