Effects of Mutations of the Glycine Gene Associated With Hyperekplexia on Central Pain Processing
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 2
- 主要终点
- Pressure pain detection threshold measured in kPA, measured with electronic pressure algometer applied at the centre of the pulp of the 2nd toe
研究概览
简要总结
Mutations in genes affecting pain transmission start to be known, the investigators are investigating a mutation in a glycine channel, which has an influence on pain modulation. Pain modulation is the ability of the central nervous system to enhance or diminish the sensation of pain. The investigators therefore will test patients and healthy volunteers with quantitative sensory tests, basically determining the point at which a stimulation just starts to induce pain. These tests are reliable and permit a direct comparison between healthy volunteers and patients with the affected glycine gene.
详细描述
Background
Hyperekplexia, also known as hereditary startle disease or stiff baby syndrome, is a rare neurogenetic non-epileptic disorder characterized by exaggerated persistent startle response and neonatal hypertonia to unexpected auditory, somatosensory and visual stimuli. Startle responses and generalized muscle stiffness both gradually subside during the first months of life. Pathological startle responses can remain throughout adulthood resulting in unprotected falls and injury.
Hereditary hyperekplexia has been identified in 70 pedigrees, most of them being characterized by the major form. Some occasional occurrence of the minor form was described in rare families, but its presence may remain clinically undetected.
The clinical diagnosis of the major form of hyperekplexia needs three mandatory features:
- Generalized stiffness after birth normalizing during the first years of life
- Excessive startling to an unexpected stimulus, particularly auditory, present from birth and remaining throughout life
- Generalized stiffness after a startle reflex that lasts a few seconds Five genes are associated with hyperekplexia, the disease being caused by mutations in the genes encoding different subunits of the inhibitory postsynaptic glycine receptor GLRA1 and GLRB. Additionally defects in the presynaptic glycine transporter gene (SLC6A5) have been recently identified in human hyperekplexia. GPHN, encoding the glycinergic clustering molecule gephyrin, and ARHGEF9, an X-linked gene encoding collybistin, are each associated with one known case of hyperekplexia.
研究设计
- 研究类型
- Interventional
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 7 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Hyperekplexia
- •Exclusion Criteria
- •Age below 7 years
- •Pregnancy
- •Breast feeding
- •Ongoing medication
- •Cognitive impairment
排除标准
- 未提供
结局指标
主要结局
Pressure pain detection threshold measured in kPA, measured with electronic pressure algometer applied at the centre of the pulp of the 2nd toe
时间窗: Within 0 to 33 seconds after the beginning of the stimulation
Pain detection thresholds will be measured with an electronic pressure algometer applied at the center of the pulp of the 2nd toe. The probe has a surface area of 1 cm2. The pressure is increased from 0 at a rate of 30kPa/s to a maximum pressure of 1000kPa. Pain detection threshold is defined as the point at which the pressure sensation turns to pain. The subjects are instructed to press a button when these points are reached. The algometer displays the pressure intensity at which the button is pressed.
次要结局
- Electric pain reflex, as measured with electromyography from the biceps femoris and the rectus femoris muscles(Within 50 to 150 ms after the beginning of stimulation)
- Heat and cold pain detection thresholds, as measured with a thermode in degrees Celsius(Within 0 to 14 seconds after the beginning of the stimulation)
- Ice water pain threshold of the hand as measured in seconds the hand was left in the water, measured with ice water container(Within 0 to 2 minutes after the beginning of the stimulation)
- Pressure pain detection threshold measured in kPA, measured with electronic pressure algometer applied at the centre of the pulp of the 2nd toe(At the end of the experiment, expected to be after 30 minutes on average)