A Mechanistic Study on Morphine-induced Orthogonal Neural Plasticity for Itch and Pain Processing in Humans (a Relation of Morphine-induced Itch and Pain Processing)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Microvascular reactivity
研究概览
简要总结
In This experiment, the investigators would like to test the two following hypotheses regarding the mechanisms by which opioids cause itch:
- Opioids cause itch by a spinal disinhibition mechanism (central nervous system (CNS) effect).
- Opioids cause itch through a mast cell-destabilizing effect leading to release of histamine and tryptase in the skin where itch is evoked (peripheral mechanism).
详细描述
Intrathecal and orally administered opioids are heavily used for the treatment of several acute pain conditions. However, while opioids are effective analgesics for acute pain, they are well-known to frequently cause itch (pruritus) as a side effect according with the two hypotheses stated above. So far, these two hypotheses have never been tested in humans.The present study describes a proposed study design for the purpose of confirming these two hypotheses in parallel in human subjects.
Primary endpoints of the study:
To evaluate changes itch and pain perception, and superficial perfusion after each itch provocations.
Secondary endpoints of the study:
To evaluate the existence of a correlation between itch sensitization and analgesic efficacy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 20 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy men and women in the age of 20-65 years
- •The participants must be able to speak and understand English
排除标准
- •Participants with any clinically significant abnormalities that in the opinion of the investigator may increase the risk associated with trial participation or may interfere with the interpretation of the trial results.
- •Pregnant or lactating female persons
- •Drug addiction defined as the use of cannabis, opioids or other drugs
- •Previous or present neurologic, musculoskeletal or mental illnesses
- •Current pain and itch causing diseases or psychiatric disorders
- •Participants unable to understand or follow the instructions
- •Participating in another study where investigational drug is used
- •Participants had known allergy/discomfort to morphine
- •Lack of ability to cooperate
研究组 & 干预措施
Morphine
Each participant will receive a single dose of 20 mg morphine tablet. At estimated peak-plasma concentration testing is conducted. The subject and the assessor are both blinded to the drug administrations.
干预措施: Morphine (Drug)
Morphine
Each participant will receive a single dose of 20 mg morphine tablet. At estimated peak-plasma concentration testing is conducted. The subject and the assessor are both blinded to the drug administrations.
干预措施: Histamine (Drug)
Morphine
Each participant will receive a single dose of 20 mg morphine tablet. At estimated peak-plasma concentration testing is conducted. The subject and the assessor are both blinded to the drug administrations.
干预措施: Cowhage (Mucuna Pruriens) (Drug)
Morphine
Each participant will receive a single dose of 20 mg morphine tablet. At estimated peak-plasma concentration testing is conducted. The subject and the assessor are both blinded to the drug administrations.
干预措施: isotonic saline (Drug)
Placebo
Each participant will receive a single dose of an identical placebo tablet. At estimated peak-plasma concentration testing is conducted. The subject and the assessor are both blinded to the drug administrations.
干预措施: Placebo oral tablet (Drug)
Placebo
Each participant will receive a single dose of an identical placebo tablet. At estimated peak-plasma concentration testing is conducted. The subject and the assessor are both blinded to the drug administrations.
干预措施: Histamine (Drug)
Placebo
Each participant will receive a single dose of an identical placebo tablet. At estimated peak-plasma concentration testing is conducted. The subject and the assessor are both blinded to the drug administrations.
干预措施: Cowhage (Mucuna Pruriens) (Drug)
Placebo
Each participant will receive a single dose of an identical placebo tablet. At estimated peak-plasma concentration testing is conducted. The subject and the assessor are both blinded to the drug administrations.
干预措施: isotonic saline (Drug)
结局指标
主要结局
Microvascular reactivity
时间窗: 10 minutes after every itch inductions
The evoked cutaneous inflammation (quantified by superficial blood perfusion) will be measured by full-field laser perfusion imaging.
Assessment of itch
时间窗: 1 minute after every itch inductions
Immediately following the itch provocations, participants will be instructed to rate the itch intensity for 10 minutes using a digital visual analogue scale (VAS; eVAS Software: Aalborg, University, Denmark), on a tablet. The scale will be measured from 0 to 100, where 0 represents 'no itch' and 100 'worst itch imaginable'.
Assessment of pain
时间窗: 1 minute after every itch inductions
Immediately following the itch provocations, participants will be instructed to rate the pain intensity for 10 minutes using a digital visual analogue scale (VAS; eVAS Software: Aalborg, University, Denmark), on a tablet. The scale will be measured from 0 to 100, where 0 represents 'no pain' and 100 'worst pain imaginable'.
次要结局
- Cold (CPT) and heat (HPT) pain thesholds(60 minutes after morphine/placebo administration)
- Pressure Pain Threshold(60 minutes after morphine/placebo administration)
研究者
Silvia Lo Vecchio
Principal Investigator
Aalborg University