Presence of Signs of Central Sensitization in Episodic and Chronic Migraine - a Cross Sectional Study

For objectifying central sensitization, both self-reported and psychophysiological measures of allodynia and hyperalgesia will be used. These symptoms are considered to be signs of central sensitization, especially when present at distant pain-free areas (9).

Therefore, 100 patients with migraine (50 EM, 50 CM) and 50 healthy controls will be recruited. The patients should meet the following inclusion criteria: 1) diagnosis of migraine headache based on the criteria of ICDH-3 and verified by a medical doctor, 2) not being pregnant or have given birth in the preceding year, 3) adults between the age of 18 years and 65 years. Exclusion criteria are: 1) any other diagnosis of headache or mixed form, 2) any structural neurological syndrome, 3) any neurological brain event in the past, 4) surgery at the head, neck or shoulder the last 3 years.

As thermal testing might be followed by a mechanical hyperalgesia (10), this protocol will start with evaluating the mechanical sensitivity and afterwards the thermal sensitivity. The mechanical sensitivity will be determined by measuring PPT (A). A standardized and reliable QST protocol (B), including detection and sensitivity to warmth and cold, will be used (11). The temporal summation (C) will be used to asses endogenous pain facilitating pathways and conditioned pain modulation (CPM) (D) will be used to assess the endogenous pain inhibitory pathways. In addition questionnaires (E) will be conducted. The patients will be tested unilateral at the painful side and interictally.

Pressure pain thresholds PPT will be performed firstly at the anterior tibial muscle halfway between the most superior attachment to the tibia and its tendon in the upper one third of the muscle belly (13) and secondly at the middle of the temporalis muscle (12), using a digital algometer (Wagner FPX 50) with a 1 cm2 rubber tip. The pressure algometer will apply a perpendicular increasing pressure (1kg/s) at the different test locations until the participant reports the first feeling of pain. The PPT of 4 series of ascending stimulus intensities, with an inter-stimulus interval (ISI) of 20sec between the different stimuli and an ISI of 60sec between the 2 locations, will be measured. The first stimulus is a familiarization stimulus. Afterwards the mean of the 3 subsequent stimuli will be calculated.

Thermal detection and pain thresholds The thermal tests will be performed unilateral at tibial anterior, thenar and the forehead, using a TSA-2 (Neuro Sensory Analyzer, MEDOC). At first cold and heat detection thresholds will be measured. The patient will be asked to indicate when they feel a change in temperature. Afterwards the patient will be asked to indicate when the stimulus becomes painful to determine the cold and heat pain thresholds. The thresholds of 4 series of stimuli will be measured. The first stimulus is a familiarization stimulus. Afterwards the mean of the 3 subsequent stimuli will be calculated for every location. The subject will push a button when the thresholds are reached. The baseline temperature will be 32°C and the stimuli will increase with 1°C/s (14). The contact area of the thermode will be 16mm x 16mm. The cut-off temperature for heat is 53°C and for cold 0°C. The ISI will be 20 seconds on one location, and 1min between different locations. After measuring a thermal detection threshold, the temperature will go back to baseline with 1°C/s and after a thermal pain threshold measurement with 5°C/s.