Marsili Syndrome
Conditions
Brief summary
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
Interventions
OTHERHistamine
To deliver histamine, standard allergy skin prick test (SPT) lancets are applied
The spicules will be manually inserted. Approximately 30-35 spicules are gently rubbed into a 1 cm diameter skin area on the forearm
Capsaicin patches (2x2 cm, dosage form: transdermal patch 8%) will be applied on the selected area. The patch will be left in place for 30 minutes after which it will be removed.
OTHERKnee Injections of hypertonic saline
Experimental knee pain will be induced with a 0.25-0.30 mL bolus injection of 5% hypertonic saline, which will be injected into the dominant Infrapatellar Fat Pad (IFP)
OTHERCold Pressure Test
Participants will be asked to place their hand in the cold-water tank (temperature around 5°C) and to keep it for as long as they can tolerate it.
OTHERComputerized Conditioned Pain Modulation (CPM)
CPM will be assessed using a double-cuff.
Sponsors
Aalborg University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Healthy men and women aged 18-80 years * Marsili syndrome * Speak and understand English
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measuring pain by computerized Visual Analog Scale Scoring | 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 Itch by computerized Visual Analog Scale Scoring | 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. |
| Alloknesis | Day 1 | Measured using a standardized sensory brush exerting a force of 200 to 400 mN. |
| Mechanically evoked itch (MEI) | 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). |
| Mechanical Pain Thresholds (MPT) | 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 Sensitivity (MPS) | Day 2 | This test is conducted with the same pinprick set used to test the MPT. |
| Pressure Pain Threshold | Day 1 | Pressure pain threshold (PPT) is obtained using a manual pressure algometer |
| Mechanical Suprathreshold Pain Stimulation | 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) | 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 | Day 1 | Spatial and temporal summation of pain will be assessed with the use of the computerized cuff pressure algometer |
| Cold Detection Thresholds (CDT) | 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) | 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) | 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) | 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) | Day 1 | The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device |
| EEG recording | 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 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Superficial blood perfusion | Day 1 | Superficial blood perfusion (SBP) is measured by a Speckle contrast imager |
| Pain Catastrophizing Scale (PCS). | Baseline | The PCS assesses negative and exaggerated coping concerning anticipated or experienced painful stimuli. Thirteen items have to be answered on a 5-point Likert-type scale ranging from 0 (Not at all) to 4 (all the time). |
| Itch Catastrophizing Scale (ICS). | Baseline | The ICS assesses negative and exaggerated coping concerning anticipated or experienced itchy stimuli. Thirteen items have to be answered on a 5-point Likert-type scale ranging from 0 (Not at all) to 4 (all the time). |
| Reinforcement Sensitivity Theory - Personality Questionnaire (RST-PQ). | Baseline | The RST-PQ contains in total, 65 items must be answered on a 4-point Likert-type scale |
| Depression, Anxiety, Stress Scale (DASS-21) | Baseline | The questionnaire measures the magnitude of depression, anxiety, and stress. Each of these three subscales consists of 7 questions answered using a 0-3 Likert scale, with 0 meaning "it did not apply to me", and 3 meaning "it applied to me very much" |
| Learned Helplessness Scale (LHS) | Baseline | The questionnaire consists of 20 items, and the participant's response to each item is rated on a 4-point Likert scale ranging from strongly agree (1) to strongly disagree (4). |
| Positive And Negative Affect Schedule (PANAS) | Baseline | Twenty words are associated with the subject's current feelings and have to be rated on a 5-points Likert-type scale, whit 0 corresponding to "not at all" and 5 corresponding to "Very". |
| Difficulties in Emotion Regulation Scale Short Form (DERS-SF) | Baseline | The questionnaire is an 18-item measure used to identify emotional regulation issues in adults. Participants rate each item on a 5-point Likert scale (from 1 to 5). |
| Emotion Regulation Questionnaire (ERQ) | Baseline | This questionnaire is designed to assess individual differences in the habitual use of two emotion regulation strategies: cognitive reappraisal and expressive suppression. Respondents answer each item on a 7-point Likert-type scale ranging from 1 (strongly disagree) to 7 (strongly agree), where 4 means (neutral). |
| The Pittsburg Sleep Quality Index (PSQI) | Baseline | Consists of seven scored from zero to 21 with higher scores reflecting a worse overall quality o: sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. |
| Multidimensional Assessment of Interoceptive Awareness (MAIA-2) | Baseline | MAIA-2 consists of 37 self-report items that evaluates multiple dimensions of interoception, distinguishing between simple detection of bodily signals and the cognitive-affective interpretation of those signals. |
| Body Perception Questionnaire (BPQ-SF) | Baseline | BPQ-SF consists of 12 self-report items designed to assess the frequency and intensity of perceived autonomic and somatic bodily sensations. |
| The International Physical Activity Questionnaire (IPAQ) | Baseline | IPAQ is a standardized self-report instrument developed to assess habitual physical activity levels |
| Mediterranean Diet Adherence Screener (MEDAS) | Baseliene | MEDAS is a validated 14-point questionnaire to evaluate dietary habits |
Countries
Denmark
Contacts
CONTACTSilvia Lo Vecchio
Outcome results
None listed