The Pain Management Programme, Walton Centre NHS Foundation Trust, Lower Lane, Liverpool, L9 7LJ, UK.
Pain Research Institute, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK.
J Transl Med. 2021 Nov 6;19(1):458. doi: 10.1186/s12967-021-03128-2.
Induction of long-term synaptic depression (LTD) is proposed as a treatment mechanism for chronic pain but remains untested in clinical populations. Two interlinked studies; (1) A patient-assessor blinded, randomised, sham-controlled clinical trial and (2) an open-label mechanistic study, sought to examine therapeutic LTD for persons with chronic peripheral nerve injury pain.
(1) Patients were randomised using a concealed, computer-generated schedule to either active or sham non-invasive low-frequency nerve stimulation (LFS), for 3 months (minimum 10 min/day). The primary outcome was average pain intensity (0-10 Likert scale) recorded over 1 week, at 3 months, compared between study groups. (2) On trial completion, consenting subjects entered a mechanistic study assessing somatosensory changes in response to LFS.
(1) 76 patients were randomised (38 per group), with 65 (31 active, 34 sham) included in the intention to treat analysis. The primary outcome was not significant, pain scores were 0.3 units lower in active group (95% CI - 1.0, 0.3; p = 0.30) giving an effect size of 0.19 (Cohen's D). Two non-device related serious adverse events were reported. (2) In the mechanistic study (n = 19) primary outcomes of mechanical pain sensitivity (p = 0.006) and dynamic mechanical allodynia (p = 0.043) significantly improved indicating reduced mechanical hyperalgesia.
Results from the RCT failed to reach significance. Results from the mechanistic study provide new evidence for effective induction of LTD in a clinical population. Taken together results add to mechanistic understanding of LTD and help inform future study design and approaches to treatment. Trial registration ISRCTN53432663.
长期突触抑制（LTD）的诱导被认为是治疗慢性疼痛的一种机制，但在临床人群中尚未得到验证。两项相互关联的研究；（1）一项患者评估者盲法、随机、假对照临床试验和（2）一项开放标签的机制研究，旨在研究慢性周围神经损伤疼痛患者的治疗性 LTD。
（1）患者使用隐蔽的、计算机生成的方案随机分为活跃组或假非侵入性低频神经刺激（LFS）组，进行 3 个月（至少每天 10 分钟）的治疗。主要结局是通过 1 周、3 个月的平均疼痛强度（0-10 级 Likert 量表）记录，比较两组之间的差异。（2）在试验完成时，同意的受试者进入一项机制研究，评估 LFS 对感觉变化的影响。
（1）共有 76 名患者被随机分配（每组 38 名），65 名（31 名活跃组，34 名假刺激组）被纳入意向治疗分析。主要结局没有统计学意义，活跃组疼痛评分降低 0.3 个单位（95%CI-1.0，0.3；p=0.30），效应大小为 0.19（Cohen's D）。报告了 2 例与设备无关的严重不良事件。（2）在机制研究中（n=19），机械性疼痛敏感性（p=0.006）和动态机械性痛觉过敏（p=0.043）的主要结局显著改善，表明机械性痛觉过敏减轻。
随机对照试验的结果未达到统计学意义。机制研究的结果为临床人群中有效诱导 LTD 提供了新的证据。综合结果增加了对 LTD 的机制理解，并有助于为未来的研究设计和治疗方法提供信息。试验注册 ISRCTN53432663。
