A prospective observational study was conducted and reported according to the STROBE criteria for observational studies. https://www.strobe-statement.org. The Ethics committee of Antwerp University Hospital approved this study (trial registration: B300201734328). All patients provided written informed consent before their participation.
Patients with migraine were recruited from primary health care centers with specific focus on and expertise in headache and neck pain. All patients were initially screened for eligibility by a telephone interview using a structured questionnaire. Patients were diagnosed according to the criteria of the International Classification of Headache Disorders (III) by a general practitioner or neurologist (14).
Patients were excluded in case of other headaches, medication overuse, rheumatoid disorder, chronic diseases (i.e. fibromyalgia), a recent history of neck/head trauma (i.e. whiplash), anaesthetic block in the past month, pregnancy and symptoms of concomitant illness. Furthermore, migraine needed to be accompanied by neck pain and a good understanding of the Dutch language was required as all information, instructions, and questionnaires were in Dutch. Patients were asked to keep a headache diary for four weeks to confirm the diagnosis and frequency of migraine. Measurements were planned interictally, and it was not allowed to take analgesics or muscle relaxants twenty-four hours before the examination.
These consisted of the completion of a headache diary (headache frequency and headache intensity), two questionnaires (Headache Impact Tests, HIT-6 and Central Sensitization Inventory), the assessment of Pressure Pain Thresholds (PPTs) and measurement of pressure during MPT.
The headache diary was used to calculate the headache frequency (days/month) and mean headache intensity on a Numerical Pain Rating Scale (NPRS). The NPRS is a scale with 11-points, with 0 indicating no pain and ten indicating as intense as one could imagine (14, 15) and is used to rate the intensity of the headache and neck pain. The mean headache intensity was calculated by dividing the sum of all NPRS-scores on headache days and the mean of all noted headache days.
The Headache Impact Test 6 (HIT-6) measures the adverse impact of headache on social functioning, role functioning, vitality, cognitive functioning and psychological distress and measures the severity of headache pain. This questionnaire consists of six items that need to be answered on a five-point scale ranging from never to always. The total score varies between 36 and 78, with a higher score according to a more significant impact. HIT-6 scores are divided into four severity levels; little or no impact (≤ 49), some impact (50–55), substantial impact (56–59) and severe impact (≥ 60). The HIT-6 is reliable and valid in patients with headaches, equally in patients with chronic migraine (16, 17).
The central sensitization inventory (CSI) is also a self-report scale designed to highlight the possible presence of a central sensitization syndrome. The first part, Part A, assesses 25 health-related symptoms common to central sensitization syndromes. Total scores range from 0-100, where a cut-off score of 40 provides a clinically relevant guide to assume the possible presence of a central sensitization syndrome (18). Part B collects the presence of previous diagnoses of seven separate central sensitization syndromes, including migraine. The Dutch version used in this study has good internal consistency for the total score on 3 out of 4 domains, good discriminative power and excellent test-retest reliability (19).
Pressure Pain Thresholds
Pressure Pain Thresholds (PPT) were assessed with the Somedic algometer with a 1 cm2 probe and are expressed in kPa/cm². This algometer has excellent construct validity and high intrarater reliability in people with migraine (20) (21). This was done by examiner 1 (E.V.), who had training for these measurements of 10 hours. In total, three measurements were performed on the midpoint of the upper trapezius, thenar and anterior tibial anterior muscle, bilaterally. The pressure was gradually increased (50kPa/sec) until the feeling of only pressure changed into the feeling of pressure and pain.
The participant had to push a button of a hand-held switch. Once the participant had pushed the button, the recorded value on the display of the algometer was noted (20).
Manual Pressure Techniques
The MPTs were performed by two musculoskeletal physiotherapists (W.D.H. and R.C.) with each over 20 years of experience in assessing and treating patients with cervical spine disorders. Four techniques were performed bilaterally.
The first two techniques are described by Watson et al. (10).The patient lies in a supine position, and pressure with the thumb is applied at the posterior arch of C1, with the participant’s head in approximately 20 degrees of contralateral rotation. By adding a slight rotation of the head towards the thumb, stress is applied to the joint of C0-1. In preparation for the second technique, pressure with the thumb is directed to the articular pillar of C2 with the participant’s head in approximately 30 degrees of contralateral rotation to passively stress the joint of C2-3.
The third and fourth techniques are performed with the patient in a prone position and the cervical spine in a neutral position. Pressure with the thumb is given deep towards the occiput to stretch the Rectus Capitis Major muscle (third technique). At a lower level, pressure with the thumb was directed towards the spinous process of C2 and attempted to stretch the Obliquus Capitis muscles. (fourth technique). A schematic representation of technique 3 and 4 is presented in Fig. 1.
The outcome of these MPTs was defined as positive (yes/no) if provocation of the familiar headache occurred within 5 seconds. In all positive cases, the intensity of the provoked pain was registered via an NPRS.
Registration of the applied thumb pressure
During the MPT, the thumb pressure of the assessor was measured constantly using force-sensing resistor sensors (1.23 cm²) that were placed on the tip of the thumb (Fig. 2) and registered by CAPTIV software (CAPTIV-L7000, www.teaergo.com). These sensors measure the applied pressure in kg/cm². During the examination, a third assessor was in control of the software so that the examiner, who performed the MPT, was blinded for the outcome on the applied pressure. The third assessor also recorded the patients reported outcome on the MPT.
NPRS scores for headache and neck pain were obtained before the measurements. When NPRS scores were ≤ 3/10, it was considered that pain did not influence the tests. PPTs were measured.
MPT measurements were performed in two steps. In the first step we verified if and at which site the familiar headache could be provoked. The outcomes of the MPTs being provocation of headache (yes/ no) and corresponding headache intensity (NPRS-score) were recorded.
In the second step, the MPTs were performed and now maintained for both the provocation ánd reduction of the referred pain to the head. Pressure was maintained until the NPRS score of the headache was reduced to < 2/10 or after a maximum of 120 seconds. During the application of the MPTs, the NPRS scores were noted every 15 seconds and the applied pressure was registered constantly via the FSR sensors.
Sufficient time was left between the two steps so there was no residual pain.
Data were analyzed with the SPSS version 27 Software (IBM Corp. Released 2020. IBM SPSS Statistics for Windows, Version 27.0. Armonk, NY: IBM Corp).
Descriptive data and headache characteristics were collected from all patients. Descriptive analysis was also performed for the outcomes of the MPT.
Normality of quantitative data was assessed by means of the Kolmogorov-Smirnov test. Parametric tests were used for quantitative data with a normal distribution. Conversely, non-parametric tests were used for qualitative data and quantitative data without normal distribution.
To study the reduction of the provoked headache, comparisons of NPRS scores before and after each trial were made via (paired samples T-test or) and across all three trials via a Friedman test. Changes in time needed to obtain the reduction were analyzed via a Friedman test and consequent Mann-Whitney U tests.
A 2-tailed p-value < .05 was chosen as the level of significance.