The Effect of Different rTMS Intervention on Acute Experimental Muscular Pain in Individuals Comorbid With Insomnia: a Pilot RCT
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Muscle damage severity: Muscle pain
研究概览
简要总结
Insomnia exacerbates pain sensitivity and impairs physiological recovery from acute musculoskeletal pain. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising non-invasive neuromodulation intervention to alleviate pain and modulate central sensory processing. However, whether rTMS can effectively mitigate insomnia-induced pain hyperalgesia and accelerate the recovery trajectory of acute musculoskeletal pain remains unclear, as does the optimal neuroanatomical stimulation target.
Building upon an established experimental pain model, this randomized, sham-controlled study aims to evaluate the restorative effects of three distinct rTMS interventions - targeting the left primary motor cortex (L M1), the right dorsolateral prefrontal cortex (R DLPFC), and a sham condition - on individuals experiencing insomnia. Following a standardized eccentric exercise protocol to induce muscle soreness, participants will receive three sessions of the allocated rTMS intervention at 0, 24, and 48 hours post-exercise. Pain sensitivity, recovery dynamics, and quantitative sensory testing (QST) metrics will be continuously monitored across the recovery timeframe.
The findings from this trial will clarify the therapeutic efficacy of rTMS in modulating acute pain under insomnia states and identify the target-specific mechanisms of cortical stimulation, offering evidence-based non-invasive interventions for musculoskeletal pain management.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adults aged 18 to 60 years
- •Right hand and foot dominant
排除标准
- •History of any chronic musculoskeletal pain or presence of existing pain during recruitment
- •Previous major injuries or surgery involving the lower limbs
- •Sleep disorders other than insomnia
- •Clinically diagnosed psychiatric disorders
- •Conditions that preclude safe rTMS or pain testing (e.g., severe head trauma, intracranial hypertension, implanted ferromagnetic devices, history of epilepsy, skin conditions at stimulation sites)
- •Contraindications to vigorous exercise identified through the physical activity readiness questionnaire (PAR-Q)
- •Work night shifts or rotating shift schedules
研究组 & 干预措施
R DLPFC
rTMS interventions targeting the right dorsolateral prefrontal cortex (R DLPFC)
干预措施: Repetitive transcranial magnetic stimulation (rTMS) on R DLPFC (Device)
L M1
rTMS interventions targeting the left primary motor cortex (L M1)
干预措施: Repetitive transcranial magnetic stimulation (rTMS) on L M1 (Device)
Sham
sham rTMS stimulation
干预措施: Sham repetitive transcranial magnetic stimulation (rTMS) (Device)
结局指标
主要结局
Muscle damage severity: Muscle pain
时间窗: Day 0 to Day 14
Muscle pain will be measured using an 11-point NRS, with 0 representing "no pain" and 10 indicating "worst imaginable pain". The Outcome will be recorded at rest, during a reach for the floor with knees straight, and during a validated hamstring provocative manoeuvre, the "taking-off shoe" test.
Muscle damage severity: Muscle soreness
时间窗: Day 0 to Day 14
Muscle soreness will be measured by an 7-point Likert scale, with 0= A complete absence of soreness," 1 = "A light soreness in the muscle felt only when touched/a vague ache," 2 = "A moderate soreness felt only when touched/a slight persistent pain," 3 = "A light muscle soreness when walking up and down stairs," 4 = "A light muscle soreness when walking on flat surface," 5 = "A moderate muscle soreness, stiffness, or weakness when walking," 6 = "A severe muscle soreness, stiffness, or weakness that limits my ability to move."
Pain sensitivity: Thermal pain threshold
时间窗: Day 7 and Day 9
Thermal thresholds will be measured with a 30 × 30 mm thermode (TSA 2, Medoc Ltd., Ramat Yishai, Israel). The thermode will be placed gently on the skin without causing deformation. Using the method of limits, temperature will increase or decrease at 1℃/second within a 0 - 51℃ range, with a baseline temperature of 32℃. Participants will press the stop button when the thermal sensation first becomes painful. The mean value of five consecutive trials will be used in the analysis.
Pain sensitivity: Mechanical pain threshold
时间窗: Day 7 and Day 9
Mechanical pain threshold will be evaluated using standardised weighted pinprick stimulators (MRC System GmbH, Heidelberg, Germany) with a 0.25mm flat contact area. Seven fixed intensities (8 mN - 512 mN) will be applied. The final threshold will be calculated as the geometric mean of the ascending and descending stimulus intensities from five series.
Pain sensitivity: Pressure pain threshold (PPT)
时间窗: Day 7 and Day 9
Pressure pain threshold (PPT) will be assessed with a digital pressure algometer (Medoc Ltd., Ramat Yishai, Israel) equipped with a 1 cm2 rubber probe. Pressure will be applied at 30 kPa per second until participants perceive pain. Three trials will be performed, and the mean scores will be calculated to determine the PPT.
Pain sensitivity: Temporal summation of mechanical pain (TSP-M)
时间窗: Day 7 and Day 9
The pinprick stimulator will assess TSP-M at 256 mN. Ten stimuli will be delivered at 1-second intervals over a 1 cm2 area. Pain intensity will be rated on an 11-point NRS after the first and the 10th stimuli. If the NRS pain rating remains 0 out of 10 for three consecutive 256 mN stimuli, intensity will be increased to 512 mN, and the trial will be repeated. TSP-M will be calculated as the NRS difference between the first stimulus and the 10th stimulus.
Pain sensitivity: Temporal summation of heat pain (TSP-H)
时间窗: Day 7 and Day 9
TSP-H will be measured with a 9 cm2 thermode (TSA 2, Medoc Ltd., Ramat Yishai, Israel). Two sequences of 10 heat pulses at 46 ℃ and 48 ℃ will be delivered with a 5-minute interval. Each pulse has a 0.5 s duration and will be delivered from a 40 ˚C baseline at a 13°C/s ramp rate and 2.5 s interstimulus interval. The participant will rate pain intensity on an 11-point NRS after each stimulus. TSP-H will be defined as the NRS difference between the 10th stimulus and the first stimulus for each temperature.
Pain sensitivity: Conditioned pain modulation (CPM)
时间窗: Day 7 and Day 9
CPM will be evaluated using a noxious conditioning stimulus (CS) and a test stimulus (TS). The CS will be contact heat applied to the dominant volar forearm between the distal third of the forearm and the ulnar styloid. Temperature will be set 1.1 °C above the participant's HPT for 120s, starting from 32 ℃ with an 8°C/s ramp using the TSA 2 device (Medoc Ltd., Ramat Yishai, Israel). During the CPM assessment, if participants could not tolerate the CS (i.e., pain intensity over 8 on the11-point NPRS) or if they reported a pain intensity below 4 on the 11-point NPRS, the temperature of the CS will be adjusted to ensure a safe and adequate stimulus intensity. The TS will be applied to the thenar eminence of the non-dominant hand using a pressure algometer (Medoc Ltd., Ramat Yishai, Israel) to determine PPT before and immediately after the CS. The CPM effect will be calculated by subtracting the PPT measured before the CS from the PPT measured after the CS.
次要结局
- Sleep Questionnaires: the Insomnia Severity Index (ISI)(Day 0 and Day 7)
- Sleep Questionnaires: The Pittsburgh Sleep Quality Index (PSQI)(Day 0 and Day 7)
- Sleep diary: Total Sleep Time(Day 0 to Day 14)
- Sleep diary: Sleep Onset Latency (SOL)(Day 0 to Day 14)
- Sleep diary: Wake After Sleep Onset (WASO)(Day 0 to Day 14)
- Sleep diary: Sleep Efficiency (SE)(Day 0 to Day 14)
- Actigraphy: Total Sleep Time (TST)(Day 0 to Day 14)
- Actigraphy: Sleep Onset Latency (SOL)(Day 0 to Day 14)
- Actigraphy: Wake After Sleep Onset (WASO)(Day 0 to Day 14)
- Actigraphy: Sleep Efficiency (SE)(Day 0 to Day 14)
- Psychological measurement: Depression, Anxiety, and Stress Scale (DASS-21)(Day 0 to Day 14)
- Psychological measurement: Pain Catastrophizing Scale (PCS)(Day 0 to Day 14)
- Psychological measurement: Fear of Pain Questionnaire (FPQ-9)(Day 0 to Day 14)
- Psychological measurement: Tampa Scale for Kinesiophobia (TSK-11)(Day 0 to Day 14)
- Physical Activity Level: International Physical Activity Questionnaire - Short Form (IPAQ-SF)(Day 0 to Day 14)