Diffuse Noxious Inhibitory Controls (DNIC): Nociceptive Modulation and Interaction With Neurocognitive Performance in Chronic Pain

Study Overview
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Brief Summary
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Diffuse noxious inhibitory control In order to quantify central sensitization in chronic pain patients, the Diffuse Noxious Inhibitory Control (DNIC) model has been used frequently. DNIC relies on painful conditioning stimulation of one part of the body to inhibit pain in another part, to remove the noise and to focus on relevant stimuli. Earlier studies provided evidence for malfunctioning of DNIC in Fibromyalgia (FM) patients. However, the cause of this impairment is not yet elucidated, and further study is required to unravel the pathophysiology of DNIC in FM. Hypothalamus-Pituitary-Adrenal (HPA) axis Besides neural mechanisms, also hormonal abnormalities could cause altered pain processing. Cortisol is released in answer to pain to suppress the pain. Given the evidence for hypofunction of the hypothalamic-pituitary-adrenal axis and the lower cortisol release in response to stressors in a proportion of FM patients and in chronic whiplash associated disorders (WAD) patients, the relation between pain and cortisol in these patients may be an interesting topic to consider. Neurocognitive performance Besides chronic pain, people with chronic WAD and FM suffer from severe concentration difficulties and decreased neurocognitive capabilities (reduced reaction time, short term memory deficits etc. The decreased neurocognitive performance is known to be related to pain severity in various chronic pain populations. It is hypothesized that malfunctioning of descending inhibitory pathways and subsequent chronic pain experience precludes optimal neurocognitive performance. Objectives The present investigation addresses the (patho)physiological mechanisms of DNIC in chronic pain populations. Firstly, patients with FM, chronic WAD and healthy controls are compared regarding functioning of DNIC, cortisol levels and response and neurocognitive performance (case-control). Secondly, the possible interaction between the functioning of DNIC, cortisol and neurocognitive performance is studied in patients with FM, WAD and healthy control subjects (cross-sectional). Thirdly, to examine whether a fatiguing neurocognitive stressor changes DNIC and cortisol levels in patients with FM, chronic WAD or healthy sedentary control subjects.

Conditions
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Fibromyalgia, Whiplash, Chronic Pain

Intervention / Treatment
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* Behavioral: Relaxation session
* Behavioral: Neurocognitive test battery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 30 FM group: comply with the diagnostic criteria for FM as defined by the American College of Rheumatology. 30 WAD group: comply with the criteria of the Quebec Task Force (grade I to III) 40 healthy pain-free control subjects Dutch speaking aged between 18 and 65 years. Exclusion Criteria: FM patients reporting a history of a whiplash trauma WAD patients fulfilling the diagnostic criteria for FM healthy control subjects cannot suffer any pain complaints cannot be pregnant or until 1 year postnatal asked to stop analgesics 48 hours prior to study participation, not to undertake physical exertion, and to refrain from consuming caffeine, alcohol or nicotine on the day of the experiment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| healthy controls<br> | Behavioral: Relaxation session<br>* 30 minutes relaxation session (audiotape)<br>Behavioral: Neurocognitive test battery<br>* the psychomotor vigilance task, span task and the stroop task on computer<br>|
| chronic whiplash patients<br> | Behavioral: Relaxation session<br>* 30 minutes relaxation session (audiotape)<br>Behavioral: Neurocognitive test battery<br>* the psychomotor vigilance task, span task and the stroop task on computer<br>|
| Fibromyalgia patients<br> | Behavioral: Relaxation session<br>* 30 minutes relaxation session (audiotape)<br>Behavioral: Neurocognitive test battery<br>* the psychomotor vigilance task, span task and the stroop task on computer<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pain inhibition efficacy | Participants are subjected to pain measurement, preceded and followed by the collection of saliva samples to analyze cortisol concentrations. Afterwards participants are randomly (by lottery) allocated to group 1 or 2. Group 1 performs a battery of neurocognitive tests and group 2 receives a relaxation session. Afterwards pain measurement with cortisol analyses is repeated. One week later the procedure is repeated, while group 1 receives the relaxation session and group 2 performs the neurocognitive test. | immediately (5 minutes) before and after intervention (relaxation or neurocognitive test battery) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| neurocognitive performance | Participants are subjected to pain measurement, preceded and followed by the collection of saliva samples to analyze cortisol concentrations. Afterwards participants are randomly (by lottery) allocated to group 1 or 2. Group 1 performs a battery of neurocognitive tests and group 2 receives a relaxation session. Afterwards pain measurement with cortisol analyses is repeated. One week later the procedure is repeated, while group 1 receives the relaxation session and group 2 performs the neurocognitive test. | once in the study design, immediately (5 minutes) preceded and followed by the pain measurements | 
| cortisol response to pain | Participants are subjected to pain measurement, preceded and followed by the collection of saliva samples to analyze cortisol concentrations. Afterwards participants are randomly (by lottery) allocated to group 1 or 2. Group 1 performs a battery of neurocognitive tests and group 2 receives a relaxation session. Afterwards pain measurement with cortisol analyses is repeated. One week later the procedure is repeated, while group 1 receives the relaxation session and group 2 performs the neurocognitive test. | immediately (1 minute) before and after pain measurements | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Whiplash associated disorder, chronic pain, neural inhibition, neuropsychological tests