Fatigue in Chronic Pain - Cognitive Functions, Emotional Aspects, Biomarkers and Neuronal Correlates - a Descriptive Comparative Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 72
- 试验地点
- 3
- 主要终点
- Inflammatory markers
研究概览
简要总结
The investigators will examine mental/cognitive as well as cognitive functions (executive functions, attention functions, processing speed, learning and memory) in 200 patients with chronic pain and 36 healthy controls. Mental fatigue will be measured with questionnaires and cognitive fatigue and cognitive functions with neuropsychological tests. As studies on patients with mild traumatic brain injury has shown that fatigue is associated with altered communication (connectivity) in the brain's attention-related networks, brain connectivity will be measure in 24 patients (women only) and 22 healthy female controls using functional magnetic resonance imaging (fMRI) technology. During the fMRI examination, participants will also perform a 20-minute vigilance task in a scanner. Studies have also shown that inflammatory biomarkers may be related to chronic pain, but inflammatory biomarkers has not been studied in relation to objective measures regarding cognition, fatigue and connectivity changes. Therefore, the patients and controls performing fMRI will also be examined with immunological biomarkers. In addition to this, a further 14 patients and 14 controls carrying out the neuropsychological testing alone will also be examined for immunological biomarkers.
The main objectives are:
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Do patients with chronic pain show more pronounced self-rated mental fatigue and cognitive fatigue compared to healthy controls and are fatigue measures related to cognitive functions such as process speed and attention functions?
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What is the relationship between cognitive impairments, mental fatigue, or fatigability and
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the duration of pain
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generalization of pain and are they affected by covariates, such as sleep disorders and degree of depression/anxiety?
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Is there an association between immunological biomarkers and cognitive functions/mental fatigue/cognitive fatigability?
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Does the connectivity in the brain of patients with chronic pain differ from healthy controls at rest as well as during activity while performing a vigilance task?
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Is there an association between connectivity in the brain and
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immunological biomarkers
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fatigability and
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results on neuropsychological tests?
详细描述
Many patients with chronic pain (CP) suffer from mental fatigue (fatigue) and cognitive dysfunction, which to a large extent contributes to difficulties returning to work and high sick leave rates. Previous research has primarily relied on subjective estimates, but then the results are affected by depression and sleep disorders. The general attitude has therefore been that fatigue is due to sleep disorders and depression.
However, fatigue is not only a subjective experience but can also be associated with impaired cognitive functioning. In patients with acquired brain injuries, fatigue has been linked to impaired attention, slower process speed and fatigue. Since objective measures have not been used in previous studies in chronic pain, it cannot be ruled out that fatigue and cognitive impairments may have similar underlying mechanisms.
To enable effective treatment, one needs to find markers that can distinguish different causes of fatigue (depression vs. impaired cognitive functions) from each other. Fatigue in cognitively demanding tasks can be such a marker, which has been shown in patients with mild traumatic brain injury and hormonal conditions. One theory is that the same mechanisms may play a role in CP.
In chronic pain the central nervous system is affected by an imbalance in the brain's pathway system, which leads to plastic changes in the brain. In particular, pain activates areas of the brain that are important for attention functions, which may explain why many patients with pain experience attention deficit disorders. Only a few studies have used objective tests to study the type and extent of cognitive problems and cognitive fatigue has not been studied before in patients with CP.
Functional MRI (fMRI) may reflect increased or decreased neuronal activity in the brain as changes in neuronal activity are linked to changes in regional blood flow (rCBF) and blood oxygenation levels (BOLD). Fatigue in mild traumatic brain injury is related to altered connectivity in the brain and that there are different neural networks that are related to subjective compared to objective measures of fatigue. Also in chronic pain, connectivity changes have been seen and that low back pain and rheumatic pain give different connectivity changes. These studies did not include fatigue and fatigue and did not link them to activity during the fMRI study itself.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Chronic pain
排除标准
- •Traumatic brain injury (including concussion and mild traumatic brain injury)
- •Extensive psychiatric problems or substance abuse
- •Congenital or acquired brain injury and / or does not live in their own home and who needs support in everyday life
- •Not sufficient knowledge of the Swedish language
- •Progressive disease
- •Use of drugs with a strong sedative effect
- •Pregnancy
- •Additional exclusion for Imaging:
- •Over 45 years of age
- •Male subjects
- •Metal objects implanted in the body or metal chips in body parts
- •Afraid of cramped spaces
- •Left-handedness
结局指标
主要结局
Inflammatory markers
时间窗: Baseline
he analyzes that will be used in this study are mainly exploratory, i.e., which proteins, metabolites and lipoproteins are identified cannot be determined in advance. Exploratory analyzes using panels for inflammation, cytokines \& chemokines and neuroinflammation comprising many proteins (72-92 substances.
Task-fMRI
时间窗: baseline
BOLD signal changes during fatiguing attention task (PVT)
D-KEFS - Color Word Test
时间窗: baseline
Inhibition of over-learned verbal responses. The test has four conditions: 1) naming colors (red, blue or green, 2) reading color words printed in black, 3) naming the color of the color words red, blue or green write in a different color than what is written, which means inhibition of an over-learned function of reading the word; 4) repeatedly switching between naming colors and reading out the printed words as quickly as possible, while at the same time the person needs to keep track of clues that indicate rule change. Contrast scores are used to examine the performance of the more complex tasks 3 and 4 and the basic tasks 1 and 2. The faster the time, the better. The number of errors is also measured
Fatigability from WAIS-III - Coding
时间窗: baseline
The subject must fill in the blank spaces with the symbol which is paired to the number during 120 seconds. Cognitive fatigue was assessed by subtracting the number of digits produced in the first 30 seconds from the number of digits produced in the last 30 seconds during the full 120-second period. A non ascending score (\< 0) is considered an indicator of cognitive fatigue. Both the total value in the difference between the production between 0-30 seconds and 91-120 seconds are measured and a dichotomized variable (non-ascending value) will be used.
Fatigability on e-prime vigilance (reaction time) task in the fMRI scanner
时间窗: baseline
The participants are instructed to push a button as quick as they can when a set of four zeroes appears in a red rectangle, and do nothing if other numbers appeared. After each response visual feedback of the reaction time is displayed. If the participant reacts at a false stimulus or if the response time of more than 1 sec. the feedback "false answer" or "no answer" is displayed respectively. The stimuli are presented at random intervals. The results are divided into quintiles and the mean reaction time is calculated for each quintile.
Resting state fMRI
时间窗: baseline
Changes in functional connectivity after performance of fatiguing attention task (PVT)
次要结局
- D-KEFS - Word Fluency Test(baseline)
- Working memory from WAIS-IV - Digit Symbol subtest - backward repetition(baseline)
- MFI-20(baseline)
- Visual Analog Scale of Fatigue(baseline)
研究者
Marika Moller
Associate Professor
Danderyd Hospital