Marsili Syndrome as a Gateway to Novel Analgesic Targets
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Measuring pain by computerized Visual Analog Scale Scoring
研究概览
简要总结
Congenital insensitivity to pain (CIP) comprises a group of rare genetic disorders caused by mutations in genes essential for pain sensing in humans. Among these, Marsili syndrome is caused by a dominant point mutation in the transcription factor ZFHX2, and it is characterized by markedly reduced sensitivity to noxious heat, mechanical injury, while other functions remain intact. this project aims to establish the first integrated, system-level characterization of Marsili syndrome by combining human sensory phenotyping with neurophysiological and molecular analyses. The study will be conducted in two sessions of approximately 4 hours each, 24 hours apart from each other
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Healthy men and women aged 18-80 years
- •Marsili syndrome
- •Speak and understand English
排除标准
- •Pregnant or breastfeeding
- •Current regular use of cannabis, opioids, cocaine, amphetamines, MDMA/ecstasy, benzodiazepines, barbiturates, hallucinogens, or other central nervous system-active recreational drugs.
- •Current use of prescription medication that may significantly affect pain perception, itch perception, cortical excitability, or inflammatory responses, including opioids, antiepileptic drugs, antidepressants, antipsychotics, systemic corticosteroids, or immunosuppressive medication.
- •Current or previous neurological disease, including epilepsy, stroke, traumatic brain injury, spinal cord injury, multiple sclerosis, Parkinson's disease, or other degenerative neurological disorders.
- •Current or previous severe psychiatric disorder, including major depression, psychosis, bipolar disorder, or severe anxiety disorder.
- •Current or previous clinically significant musculoskeletal, cardiovascular, pulmonary, inflammatory, autoimmune, or dermatological disease that may interfere with study procedures or outcome measures.
- •Lack of ability to understand study information, provide informed consent, or cooperate with study procedures.
- •Abnormally disrupted sleep during the 24 hours before the experiment.
- •Contraindications to TMS, including previous epileptic seizure, implanted electronic medical devices, metal implants in the head or jaw, implanted hearing aids, facial metal implants, permanent makeup, or tattoos in the facial area.
- •Inability to pass the Transcranial Magnetic Stimulation Adult Safety Screen.
- •Abnormally disrupted sleep in the 24 hours preceding the experiment
研究组 & 干预措施
Marsili group
干预措施: Cowhage (Mucuna Pruriens) (Other)
Marsili group
干预措施: Capsaicin 8% Patch (Drug)
Marsili group
干预措施: Knee Injections of hypertonic saline (Other)
Marsili group
干预措施: Cold Pressure Test (Other)
Marsili group
干预措施: Computerized Conditioned Pain Modulation (CPM) (Other)
Marsili group
干预措施: Histamine (Other)
结局指标
主要结局
Measuring pain by computerized Visual Analog Scale Scoring
时间窗: Day 1
We will ask the subjects to rate the sensation of pain on a scale from 0 to100, where 0 represents no pain and 100 represent the worst imaginable pain.
Measuring pain by computerized Visual Analog Scale Scoring
时间窗: Day 2
We will ask the subjects to rate the sensation of pain on a scale from 0 to100, where 0 represents no pain and 100 represent the worst imaginable pain.
Measuring Itch by computerized Visual Analog Scale Scoring
时间窗: Day 1
We will ask the subjects to rate the sensation of itch on a scale from 0 to100, where 0 represents no itch and 100 represent the worst imaginable itch.
Pressure Pain Threshold
时间窗: Day 2
Pressure pain threshold (PPT) is obtained using a manual pressure algometer
Measuring Itch by computerized Visual Analog Scale Scoring
时间窗: Day 2
We will ask the subjects to rate the sensation of itch on a scale from 0 to100, where 0 represents no itch and 100 represent the worst imaginable itch.
Alloknesis
时间窗: Day 1
Measured using a standardized sensory brush exerting a force of 200 to 400 mN.
Alloknesis
时间窗: Day 2
Measured using a standardized sensory brush exerting a force of 200 to 400 mN.
Mechanically evoked itch (MEI)
时间窗: Day 1
MEI is measured by using mildly pruritic, non-painful von Frey nylon filaments of a predetermined intensity (generally 5-30 miliNewton of force).
Mechanically evoked itch (MEI)
时间窗: Day 2
MEI is measured by using mildly pruritic, non-painful von Frey nylon filaments of a predetermined intensity (generally 5-30 miliNewton of force).
Mechanical Pain Thresholds (MPT)
时间窗: Day 1
This test is conducted using a pinprick set. The set consists of 7 needles each with a diameter of 0.6 mm and different force applications: 8, 16, 32, 64, 128, 256, and 512 mN.
Mechanical Pain Thresholds (MPT)
时间窗: Day 2
This test is conducted using a pinprick set. The set consists of 7 needles each with a diameter of 0.6 mm and different force applications: 8, 16, 32, 64, 128, 256, and 512 mN.
Mechanical Pain Sensitivity (MPS)
时间窗: Day 2
This test is conducted with the same pinprick set used to test the MPT.
Mechanical Pain Sensitivity (MPS)
时间窗: Day 1
This test is conducted with the same pinprick set used to test the MPT.
Pressure Pain Threshold
时间窗: Day 1
Pressure pain threshold (PPT) is obtained using a manual pressure algometer
Mechanical Suprathreshold Pain Stimulation
时间窗: Day 2
Once PPT has been determined, stimuli of 130% of the PPT will be delivered to the limb or shoulder to create a sensation of subjective mild/moderate pain
Computerized Cuff Pressure Algometer (CPA)
时间窗: Day 1
A computer-controlled cuff pressure algometer works by inflating a cuff/tourniquet, which is similar in design to those used for measuring blood pressure
Spatial and Temporal Summation of Pain
时间窗: Day 1
Spatial and temporal summation of pain will be assessed with the use of the computerized cuff pressure algometer
Cold Detection Thresholds (CDT)
时间窗: Day 1
The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device
Cold Detection Thresholds (CDT)
时间窗: Day 2
The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device
Warm Detection Thresholds (WDT)
时间窗: Day 1
The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device
Warm Detection Thresholds (WDT)
时间窗: Day 2
The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device
Cold Pain Thresholds (CPT)
时间窗: Day 1
The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device
Cold Pain Thresholds (CPT)
时间窗: Day 2
The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device
Heat Pain Thresholds (HPT)
时间窗: Day 1
The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device
Heat Pain Thresholds (HPT)
时间窗: Day 2
The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device
Pain to Supra-threshold Heat Stimuli (STHS)
时间窗: Day 1
The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device
Pain to Supra-threshold Heat Stimuli (STHS)
时间窗: Day 2
The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device
EEG recording
时间窗: Day 1
The EEG signal will be acquired constantly through 64 electrodes placed on the scalp according to the international 10-20 system with a standard EEG cap
Measuring cortical responses to magnetic stimulation
时间窗: Day 1
Transcranial magnetic stimulation (TMS) will be used to evoke cortical responses (TMSevoked potentials - TEPs) in the left and right motor cortex with a figure-eight-shaped cone coil (200 pulses for each target).
次要结局
- Superficial blood perfusion(Day 1)
- Superficial blood perfusion(Day 2)
- Pain Catastrophizing Scale (PCS).(Baseline)
- Itch Catastrophizing Scale (ICS).(Baseline)
- Reinforcement Sensitivity Theory - Personality Questionnaire (RST-PQ).(Baseline)
- Depression, Anxiety, Stress Scale (DASS-21)(Baseline)
- Learned Helplessness Scale (LHS)(Baseline)
- Positive And Negative Affect Schedule (PANAS)(Baseline)
- Difficulties in Emotion Regulation Scale Short Form (DERS-SF)(Baseline)
- Emotion Regulation Questionnaire (ERQ)(Baseline)
- The Pittsburg Sleep Quality Index (PSQI)(Baseline)
- Multidimensional Assessment of Interoceptive Awareness (MAIA-2)(Baseline)
- Body Perception Questionnaire (BPQ-SF)(Baseline)
- The International Physical Activity Questionnaire (IPAQ)(Baseline)
- Mediterranean Diet Adherence Screener (MEDAS)(Baseliene)
研究者
Silvia Lo Vecchio
Associate professor
Aalborg University