Painful Channelopathies Study
试验速览
- 阶段
- 不适用
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Pain score
研究概览
简要总结
To understand the pathophysiological basis of heritable pain syndromes. This will consist of a number of components:
- Determine the genetic basis for heritable pain syndromes.
- Investigate the pain symptoms, psychological co-morbidity and quality of life in patients with heritable pain syndromes.
- Use quantitative sensory testing to investigate abnormalities in sensory processing.
- Use imaging modalities to investigate the neural correlates of pain perception in heritable channelopathies.
- In select patients to perform skin biopsy to determine if there has been any damage to C-fibres.
- To perform skin biopsy in order to culture fibroblasts and neural crest stem cells for future studies into the molecular basis of altered pain perception.
- To use neurophysiological tests, the axon reflex, and conditioning challenges to determine how peripheral nerves, in heritable channelopathies and unusual pain syndromes, have been altered.
- Microneurographic recordings for directly detecting the function of pain fibres in peripheral nerves. Knowledge gained from the study will be used to aid the further development of genetic testing and specific pain questionnaires for the diagnosis of heritable pain syndromes secondary to channelopathies.
- Ultimately better knowledge of underlying pathophysiology in these heritable pain conditions may inform the development of novel treatments.
详细描述
Very little is currently known about the sensory characteristics and central processing of pain in patients with heritable channelopathies. The investigators will carefully study the phenotype of such patients in terms of pain symptomatology, sensory processing as revealed by quantitative sensory testing and correlate this with genotype. In select patients the investigators will perform skin biopsy to determine whether there is any evidence of damage to small fibres and would also like to generate fibroblast and neural crest stem cell cultures for future studies of the molecular basis for channel dysfunction.
The study will provide new insights into the peripheral and central nervous system mechanisms involved in the processing of pain.
The investigators will restrict themselves to channelopathies causing somatic pain syndromes and will not be investigating migraine. The following conditions will be considered: Erythromelalgia, Paroxysmal extreme pain disorder, Familial episodic pain syndrome, patients with episodic pain symptoms for which a cause cannot be found and patients with reduced pain sensibility.
1.2.1 Quantitative sensory testing (QST)
QST is a method for accurately determining sensory thresholds in human skin and is particularly useful for determining dysfunction in the nociceptive smaller diameter nerve fibres, although the precise utility of QST in routine clinical neuropathic pain management perhaps requires some further evaluation. There is also increasing interest in using QST in combination with assessment of pain descriptors to give insights into the underlying pathophysiological mechanisms of chronic pain. For example, the presence of brush evoked dynamic allodynia indicates sensitisation at the spinal level. The investigators will use a standardized protocol developed by the german neuropathic pain consortium in which they have great experience. Only limited studies have been performed on inherited painful channelopathies in assessing sensory function. The investigators will correlate findings in QST with pain symptoms and quality of life. The investigators would like to see if specific abnormalities of sensory processing are associated with particular channelopathies.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients who are ≥16 years of age who have a set of symptoms that resemble those seen on Paroxysmal Extreme Pain Disorder, Familial Episodic Pain Syndrome or Erythromelalgia.
- •Patients already with the diagnosis of Paroxysmal Extreme Pain Disorder or Familial Episodic Pain Syndrome or Erythromelalgia.
- •Patients with reduced pain sensibility.
- •First degree relatives of patients who meet diagnostic criteria for Paroxysmal Extreme Pain Disorder, Familial Episodic Pain Syndrome, Erythromelalgia or inability to experience pain.
- •Patients who do not fulfill any of the exclusion criteria.
排除标准
- •Pregnant subjects.
- •Subjects with insufficient command of English to obtain consent from or to complete the study questionnaires.
- •Subjects with insufficient mental capacity to obtain consent from or to complete the study questionnaires.
- •Subjects with concurrent severe psychological or psychiatric disorders, specially those patients with severe claustrophobia.
- •Patients with moderate to severe pain arising as a consequence of other disorders causing pain but that are not associated with those mentioned before as channelopathies.
- •Patients with central nervous system diseased that may complicate the somatosensory testing.
- •The skin biopsy procedure, will not be conducted on those patients with contraindications to do so i.e. anticoagulation therapy, skin infections, etc; that might result in adverse outcomes (if the subject decides to decline the skin biopsy, the inclusion on the study will not be affected).
- •The functional magnetic resonance imaging (fMRI) component will not be performed in subjects that had medical interventions with any device likely to be damaged or moved from its place, at any moment during the fMRI scanning procedure (including cerebral coils or clips, heart pacemakers or defibrillators, heart valve prosthesis, medicine infusion pumps, inner ear implants, neural stimulators, brain shunts, joint replacements/ large metal implants, stents in the heart or arteries, some implants, or some intra-uterine contraceptive devices.
- •Those patients that in the concept of the research team unsuitable for participation in the study.
- •For those undergoing microneurography presence of edema (swelling) or any skin condition at the ankle level that may interfere with the microneurography procedure.
- •Patients with a history of skin allergy or sensitivity will not undergo testing of axon reflex or conditioning challenges.
结局指标
主要结局
Pain score
时间窗: Day 7
Seven days pain diary of 4 or above. Patients will have 7-days pain diaries with a numeric rating scale from 0 to 10.
次要结局
- Pain related anxiety(Day 1)
- Age(Day 1)
- Nerve Conduction Studies(Day 1)
- Microneurography Studies(Day 1)
- Axon reflex measurement(Day 1)
- Functional Magnetic Resonance Imaging(Day 30)
- Gender(Day 1)
- Detailed medical history(Day 1)
- Ethnicity(Day 1)
- Measures of quality of life(Day 1)
- Measures of sleep interference(Day 1)
- Sensory Thermal Thresholds(Day 1)
- Skin biopsy(Day 1)
- Sensory Mechanical Detection Thresholds(Day 1)
- Blood samples - DNA(Within 6 months of visit)
- Intra-Epidermal Nerve Fibre density(Day 1)