Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
Scleroderma Unit, Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
RMD Open. 2023 Aug;9(3). doi: 10.1136/rmdopen-2023-003265.
Systemic sclerosis (SSc) is an autoimmune disease with health-related quality of life (HRQoL) high impairment. Pain is of paramount importance to be targeted by therapeutical approaches. Our study aim was to perform an add-on device-based non-invasive neuromodulatory treatment through transcutaneous auricular vagal nerve stimulation (tVNS) in patients with SSc, assessing its effects on pain as primary endpoint and on inflammation, cardiovascular autonomic control and HRQoL.
Thirty-two patients with SSc were enrolled based on reported pain assessed through Numeric Rating Scale (NRS). Twenty-one (90% with limited cutaneous SSc) completed a randomised, cross-over, patient-blind trial, in which interventional and active control were used in random order for 4 weeks, interspersed with 4 weeks washout. NRS, Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) Item4 for pain interference, heart rate variability (HRV), serum cytokines and HRQoL questionnaires (Health Assessment Questionnaire, Patient Health Questionnaire-9, University of California, Los Angeles Gastrointestinal Tract, Pittsburgh Sleep Quality Index) were assessed at baseline, at T1 (after 1 month of tVNS or active control), at T2 (after washout) and at T3 (after 1 month of active control or tVNS). T-test for paired data and Wilcoxon signed-rank test for non-normally distributed parameters were performed to compare the effect of tVNS and active control.
NRS pain was significantly reduced by tVNS and not by active control (Mean±SD: -27.7%±21.3% vs -7.7%±26.3%, p=0.002). Interleukin-6 was downregulated in tVNS versus active control (p=0.029). No significant differences were observed in tVNS versus active control for PROMIS-29 Item4, QoL scales and HRV with both spectral and symbolic analyses.
tVNS demonstrated to be a safe and non-invasive add-on tool to reduce pain in SSc.
系统性硬化症（SSc）是一种自身免疫性疾病，对健康相关生活质量（HRQoL）有严重影响。疼痛是治疗的重点。我们的研究目的是通过经皮耳迷走神经刺激（tVNS）对 SSc 患者进行附加设备的非侵入性神经调节治疗，评估其作为主要终点的疼痛效果，以及炎症、心血管自主控制和 HRQoL。
根据数字评分量表（NRS）评估的疼痛报告，招募了 32 名 SSc 患者。21 名（90%为局限性 SSc）完成了一项随机、交叉、患者盲法试验，其中干预和主动对照以随机顺序使用 4 周，间隔 4 周洗脱期。在基线、T1（tVNS 或主动对照治疗 1 个月后）、T2（洗脱后）和 T3（主动对照或 tVNS 治疗 1 个月后）时评估 NRS、患者报告的结局测量信息系统-29（PROMIS-29）第 4 项用于疼痛干扰、心率变异性（HRV）、血清细胞因子和 HRQoL 问卷（健康评估问卷、患者健康问卷-9、加利福尼亚大学洛杉矶胃肠道、匹兹堡睡眠质量指数）。使用配对数据的 t 检验和非正态分布参数的 Wilcoxon 符号秩检验比较 tVNS 和主动对照的效果。
tVNS 显著降低了 NRS 疼痛，而主动对照则没有（平均±标准差：-27.7%±21.3%对-7.7%±26.3%，p=0.002）。与主动对照相比，白细胞介素-6 在 tVNS 中下调（p=0.029）。与主动对照相比，tVNS 对 PROMIS-29 第 4 项、生活质量量表和 HRV 的 HRV 均无明显差异，包括光谱和符号分析。
tVNS 被证明是一种安全且非侵入性的附加工具，可减轻 SSc 患者的疼痛。
