Exploring Pain Modulation Mechanisms: A Study of TMS and Repeated Conditioned Pain Modulation
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 75
- 试验地点
- 2
- 主要终点
- Conditioned Pain Modulation as an assessment
研究概览
简要总结
Conditioned pain modulation (CPM) is the behavioral measure of diffuse noxious inhibitory control (DNIC), an endogenous pain inhibitory pathway in which pain inhibits pain. CPM is less efficient in individuals with chronic pain conditions, and it is a predictor for the development of chronic pain. Continuous stimulation of central/cortical mechanisms through engaging CPM might alter pain processing and improve pain inhibition. Transcranial Magnetic Stimulation (TMS) is a valuable tool for assessing how effectively the brain's central and cortical mechanisms engage in pain inhibition, particularly through pathways like CPM.
While alterations in cortical excitability related to analgesic-induced pain inhibition have been documented, the effects of continuous stimulation of central pain pathways, along with the mediating influence of psychosocial factors, remain underexplored. This study aims to investigate the central pain modulatory mechanisms, as assessed by CPM, and cortical excitability, as measured by TMS, in healthy participants. Additionally, the study will evaluate the impact of sociocultural factors, including ethnic identity, optimism, resilience, perceived stress, and marginalization, on the magnitude and efficiency of CPM responses.
The successful completion of this research will determine how cortical excitability changes due to training and whether these changes are mediated by psychosocial factors.
详细描述
Background:
Pain and Its Burden
Pain is a prevalent and complex health condition that significantly impacts individuals, families, and society as a whole. Of the 39.4 million adults experiencing pain most days and persisting for over three months, nearly two-thirds report it as "constantly present," with over half describing it as "unbearable and excruciating" . Pain can be categorized into physiological and pathological types. Nociceptive and inflammatory pain are physiological responses that serve protective and adaptive functions, whereas pathological pain is considered non-protective and maladaptive.
Central Mechanisms in Pain Modulation
Laboratory-based quantitative sensory testing (QST) evaluates sensory function using psychophysical methods, teasing out components of the nervous system that demonstrate loss or gain of sensory function contributing to pain. The conditioned pain modulation (CPM) paradigm is a dynamic QST measure of a pain inhibitory process in which pain sensitivity in one area decreased in response to a remotely applied painful stimulus and is used to assess the ability of the person to endogenously inhibit pain. CPM may be a valuable tool in directing mechanistic-based approaches for treating painful conditions. For example, individuals with painful diabetic neuropathy and poorly functioning CPM have more significant analgesia when given duloxetine, a medication that augments conditioned pain modulation. Additionally, identifying and treating the source of pain is associated with positive changes in CPM. Healthy individuals demonstrate more efficient CPM when compared with people in pain and a systematic review of adults with chronic pain revealed that CPM efficiency improves after a reduction in clinical pain. For example, total hip arthroplasty for treating painful osteoarthritis reduces joint pain and improves post-operative CPM. Collectively, these studies suggest that the CPM test has the potential to predict risk and treatment outcomes for chronic pain, therefore CPM may be considered an essential treatment moderator and mediator.
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
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •pain-free
- •between 18-75 years old.
排除标准
- •Participants will not be excluded based on race or gender but will be excluded if they meet any of the following:
- •non-English speaking
- •systemic medical condition is known to affect sensation
- •regular use of prescription pain medication to manage pain
- •current or history of chronic pain condition
- •currently using blood thinning medication
- •any blood clotting disorder such as hemophilia
- •any contraindication to the application of ice or cold packs, such as uncontrolled hypertension, cold urticaria, cryoglobulinemia, paroxysmal cold hemoglobinuria, and circulatory compromise
- •involved in vigorous physical activities like heavy lifting, digging, aerobics or fast bicycling
- •metal in the head or eyes, pacemakers, shunts, or lines, history of craniotomy, history of focal seizures
- •Migraine and persistent headaches.
研究组 & 干预措施
No Exposure (NE)
Participants will receive only two sessions in total: questionnaires, quantitative sensory testing, and TMS as an outcome at both sessions.
High Exposure (HE)
Participants will receive five sessions total: four sessions of the Intervention, CPM and TMS as an outcome in every session and questionnaires and QST as an outcome in the first and fifth sessions.
干预措施: Conditioned Pain Modulation (CPM) (Behavioral)
Low Exposure (LE)
Participants will receive only two sessions in total: one session of the intervention, questionnaires, quantitative sensory testing, CPM and TMS as an outcome at both sessions.
干预措施: Conditioned Pain Modulation (CPM) (Behavioral)
结局指标
主要结局
Conditioned Pain Modulation as an assessment
时间窗: Two-weeks
Participants will receive a testing stimulus of pressure applied per ascending intensity at the web space of the foot until the pain reaches 40 out of 100, then discontinued. After testing the stimulus, Participants will receive a conditioning stimulus contact heat stimulus applied to the thenar of the left hand for 60 s at an intensity of 46.5 ◦C. Subjects will be asked to rate the heat pain during the four 60-second trials. Subjects will be instructed that they may remove their hand at any time if the heat is intolerable. After 60 seconds, the contact heat will be completely removed, and the testing stimulus will be re-applied to the web space of the dominant foot. Conditioned pain modulation will be calculated as the average pain ratings of the second testing stimulus series minus the average pain ratings of the first testing stimulus series. Negative numbers indicate efficient pain modulation
Transcranial Magnetic Stimulation
时间窗: Two-weeks
Individuals meeting the TMS safety criteria will undergo baseline TMS to determine the resting motor threshold, short-interval intracortical inhibition (SICI) protocols. Both are established, reliable, valid protocols to measure motor cortical excitability and inhibition, respectively. TMS will be delivered using a D702 coil connected to Magstim 2002 magnetic stimulators via a Bistim unit (Magstim, UK). A resting motor threshold, defined as the stimulus intensity required to elicit a 50uV motor evoked potential in 5 out of ten TMS stimuli at the motor hotspot for dominant abductor pollicis brevis (APB) muscle will be determined with the participant seated, both shoulders in neutral, forearm supinated, and palms resting on a pillow in their lap. Twenty pulses of 1mV peak to peak motor evoked potentials will be recorded to assess cortical excitability. SICI will be investigated by applying a subthreshold conditioning stimulus before the test stimulus using a 1ms (SICI1ms) or a 3ms (SICI
Quantitative Sensory Testing
时间窗: Two-weeks
Slow Ramp Protocol: A computer-controlled TSAII NeuroSensory Analyzer (Medoc, Inc.) will deliver a thermal stimulus to the dominant forearm, starting at 35°C and increasing to 51°C in 1°C increments, each lasting 1 seconds. Participants will report when the sensation changes from warmth to pain (pain threshold) and when it becomes intolerable (pain tolerance). The procedure will be repeated twice with a pseudorandom interval (1 sec/min), and average thresholds and tolerances will be analyzed. Post-Stimulus Ratings: Participants will rate pain every 10 seconds for 60 seconds after the thermode is removed. These ratings primarily reflect C-fiber-mediated responses. Pressure Pain Threshold: Using an algometer with a 1 cm rubber tip, pressure will be applied at 1 kg/s to the first dorsal interosseous muscle of the dominant hand. Participants will report when the sensation changes from pressure to pain (pain threshold). The procedure will be repeated twice. Average will be calculated.
次要结局
未报告次要终点
研究者
Priyanka Rana, PT, MPT, PhD
Assistant Professor
University of Texas, El Paso