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

• neurocognitive performance [ Time Frame: once in the study design, immediately (5 minutes) preceded and followed by the pain measurements ] [ Designated as safety issue: No ]

  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.

• cortisol response to pain [ Time Frame: immediately (1 minute) before and after pain measurements ] [ Designated as safety issue: No ]

  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.

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.

1. Firstly, patients with FM, chronic WAD and healthy controls are compared regarding functioning of DNIC, cortisol levels and response and neurocognitive performance (case-control).
2. 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).
3. Thirdly, to examine whether a fatiguing neurocognitive stressor changes DNIC and cortisol levels in patients with FM, chronic WAD or healthy sedentary control subjects.

Thirty patients with FM, 30 patients with WAD and 30 healthy pain-free control subjects will be enrolled. All three groups will be comparable for age, gender, education level and socioeconomic status; both patient groups will be comparable for illness duration. Sample size was calculated based on a power analysis (0.80), based on the assumption of a 20% difference of DNIC functioning after neurocognitive testing.

• Fibromyalgia
• Whiplash
• Chronic Pain

• Behavioral: Relaxation session
  30 minutes relaxation session (audiotape)
• Behavioral: Neurocognitive test battery
  the psychomotor vigilance task, span task and the stroop task on computer

• healthy controls
  Interventions:

  • Behavioral: Relaxation session
  • Behavioral: Neurocognitive test battery
• chronic whiplash patients
  Interventions:

  • Behavioral: Relaxation session
  • Behavioral: Neurocognitive test battery
• Fibromyalgia patients
  Interventions:

  • Behavioral: Relaxation session
  • Behavioral: Neurocognitive test battery

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.