Sage Journals: Discover world-class research

Abstract

Aim To assess the efficacy of pain neuroscience education combined with physiotherapy for the management of migraine.

Background Physiotherapy can significantly reduce the frequency of migraine, but the evidence is based only on a few studies. Pain neuroscience education might pose a promising treatment, as it addresses migraine as a chronic pain disease.

Methods In this non-blinded randomized controlled trial, migraine patients received physiotherapy + pain neuroscience education or physiotherapy alone, preceded by a three-month waiting period. Primary outcomes were frequency of headache (with and without migraine features), frequency of migraine and associated disability.

Results Eighty-two participants were randomized and analyzed. Both groups showed a decrease of headache frequency (p = 0.02, d = 0.46) at post-treatment (physiotherapy: 0.77 days, 95%CI: −0.75 to 2.29 and physiotherapy + pain neuroscience education: 1.25 days, 95%CI: −0.05 to 2.55) and at follow-up (physiotherapy: 1.93, 95%CI: 0.07 to 3.78 and physiotherapy + pain neuroscience education: 3.48 days, 95%CI: 1.89 to 5.06), with no difference between groups (p = 0.26, d = 0.26). Migraine frequency was reduced significantly in the physiotherapy + pain neuroscience education group, and not in the physiotherapy group, at post-treatment (1.28 days, 95%CI: 0.34 to 2.22, p = 0.004) and follow-up (3.05 days, 95%CI: 1.98 to 5.06, p < 0.0001), with a difference between groups at follow-up (2.06 days, p = 0.003). Migraine-related disability decreased significantly in both groups (physiotherapy: 19.8, physiotherapy + pain neuroscience education: 24.0 points, p < 0.001, d = 1.15) at follow-up, with no difference between groups (p = 0.583). Secondary outcomes demonstrated a significant effect of time with no interaction between time and group. No harm or adverse events were observed during the study.

Conclusion In comparison to physiotherapy alone, pain neuroscience education combined with physiotherapy can further reduce the frequency of migraine, but had no additional effect on general headache frequency or migraine-related disability.

Trial Registration The study was pre-registered at the German Clinical Trials Register (DRKS00020804).

Keywords

Migraine pain neuroscience education physiotherapy neck pain headache

Introduction

The pathophysiology of migraine is based on cyclic changes within the central nervous system, associated with a cascade of events provoking a heightened sensitivity of the trigeminal nervous system and associated symptoms such as phono- and photophobia, nausea and vomiting (1,2). The most frequently associated symptom is neck pain (3,4) and an increasing body of evidence reports on musculoskeletal findings, including trigger points in neck and face muscles, joint hypomobility, posture or range of motion changes of the cervical spine, which are significantly more prevalent in patients with migraine than in control participants (5 –9). While some authors explain such findings as the consequence of repeated migraine attacks influencing the musculoskeletal system, others hypothesize that the nociceptive input originating from the cervical muscles and joints would influence the attack frequency and thereby potentially contribute to the transition to chronic migraine (10,11). Indeed, more severe migraine presentations are associated with more musculoskeletal findings but the difference between chronic and episodic migraine is less pronounced than between migraine patients and healthy participants (10,12). Head pain referral during manual palpation of upper cervical structures (13 –15) points towards a connection between the occipital, upper cervical and trigeminal nerves, indicating a convergence of afferences at brainstem level within the trigeminocervical complex (16,17). A reciprocal connection can be inferred from preliminary data indicating a reduced headache frequency after physiotherapy focusing on cervical musculoskeletal structures (18,19), but there is currently no evidence from methodologically rigorous randomized controlled trials.

Although migraine is a condition with alternating painful and pain-free intervals, it can also be understood as a chronic pain disease (20,21). The term “chronic” is somewhat misleading because the international headache classification describes chronic migraine based on the frequency of attacks (22) rather than on the duration of the disease or underlying central nervous system changes, as defined by the International Association for the Study of Pain for other chronic pain conditions (23). In contrast to episodic migraine, chronic migraine is associated with a greater sensitization and can exhibit pain features of other primary headaches, such as chronic tension type headache (24,25). However, both migraine forms share features of chronic pain by showing characteristic sensory alterations (26,27), altered endogenous pain modulation (28) and by associated psychophysical features such as impaired sleep and the influence of stress (29,30). Similar to other chronic pain conditions, migraine is also characterized by altered central nervous system processing (31).

Guideline-recommended treatment for chronic pain conditions is mainly exercise-based and includes multimodal cognitive behavioral treatment (32). A dominant feature of such programs is pain neurophysiology education (PNE), which is a structured approach to teach patients the physiological processes underlying ongoing pain (33 –35). The mechanism of action of this established cognitive-behavioral intervention for adults with chronic pain is based on changing maladaptive illness beliefs and subsequently altering behavior. PNE takes into account the individual behavioral, psychological, and environmental factors that may contribute to a patient’s pain persistence.

Although education in general has been shown to be an important component of migraine management (36), the effectiveness of PNE has not been evaluated in migraine populations. Only recently, a scoping review highlighted that there is a lack of PNE studies in migraine populations (37).

The aim of this study was therefore to evaluate the additional effect of PNE, adapted to the pathophysiology of migraine, on headache frequency, migraine frequency and headache associated disability, when provided as an add-on to physiotherapy. Our hypothesis is that adding PNE to usual physiotherapy treatment would lead to additional improvements in headache frequency, disability, neck pain and psychosomatic outcomes.

Methods

Study design

This randomized controlled trial featured two intervention arms, physiotherapy plus pain neuroscience education (PT + PNE) or physiotherapy alone (PT). Effects were compared within and between groups. The study was stopped after recruitment goals were met. Ethical consent was granted from the ethics committee of the University of Luebeck (process number 19-362) and all participants provided written consent before enrollment. The reporting follows the recommendations of the CONSORT Statement for the Standardized Reporting of Randomized Clinical Trials (38).

Participants

Participants aged between 18–66 years diagnosed with migraine (migraine on >4 days per month) with or without neck pain were included in the study. Migraine was diagnosed according to the current diagnostic criteria of the International Classification of Headache Disorders (22). Patients with additional psychiatric or neurological diseases or concomitant other headache types (except for episodic tension-type headache) were excluded. Participants were instructed to continue with ongoing prophylactic therapies without any changes, and to not start any further therapy such as physiotherapy during participation in the study. Participants were consecutively recruited by placing information brochures at local neurology and primary care clinics in the region, advertising at local support groups (Migraine League) and physical therapy practices, and on the local University of Applied Health Sciences website, as well as through advertisements in daily newspapers and social media.

Interventions

Physiotherapy and PNE were provided by one physiotherapist (RM) experienced in the treatment of headache patients (>10 years) and with additional training in manual therapy (OMPT). Interventions were conducted at the University of Applied Health Sciences in Bochum, Germany, and at two local physical therapy clinics. Following a thorough physical examination, based on an international consensus procedure (39) and previously evaluated for the use in migraine populations (12), all patients received six sessions (30 minutes each) of tailored physiotherapy consisting of strengthening exercises for the neck and shoulder girdle muscles, mobilization of the cervical and thoracic spine, coordination and posture exercises and soft-tissue mobilization. The choice and combination of interventions was based on the findings from the physical examination. In addition, home exercises were provided to both groups in order to complement the intervention and to support self-efficacy.

In this study we used a simple, unrestricted randomization and the allocation of treatment was randomized without constraints. Each participant could choose one of two sealed, opaque envelopes after the baseline assessment. Thus, with two treatments, the equivalent to a coin toss for each patient, without regard to balance, each participant had an equal chance of receiving each of the treatments. The randomization ratio was 1: 1, based on two study arms.

An allocation order as well as an assignment of the participants was not needed, as the participants chose and opened one of the two closed envelopes themselves. After reviewing the inclusion criteria, providing informed consent and obtaining written consent, enrollment in the study was performed by the treating therapist.

Patients randomized to the PT + PNE group additionally received approximately 15 minutes of theory classes after each physiotherapy session. Contents of the PNE were based on the PNE literature for chronic pain (33,40 –43), supplemented and adapted to the specific aspects of migraine. As the study was conducted in Germany, PNE was provided in German. The education included nine topical areas (provided in six sessions) which are summarized in Table 1. Neither the therapist nor patients were blinded towards group allocation.

Table 1.

Topics for the pain neuroscience education.

Session	Topic	Content
1	The alarm systemNociceptors	Acute pain is a biologically important danger or warning sign. All human tissues, including the meninges, contain local sensors/nociceptors. Sensors in the neck or head area can send alarm signals to the brain. Sensors are not necessary to feel pain. Pain and tissue damage are not related.
2	Trigeminocervical convergenceThe brain	Through close connections via the trigeminal complex, the upper neck, facial and temporomandibular regions may influence each other. Pain is solely an output of the brain. Pain occurs whenever the brain perceives that there is a threat. This may also be the case when many warning signals arrive simultaneously at the brain.
3	Activity of different brain regionsChronification of pain	Pain involves many areas of the brain simultaneously, including neurons that control movement, cognition, memory, autonomic regulation, sensory discrimination and fear. Frequently recurring pain can result from an overexcited nervous system (NS) and no longer has a warning function. Thoughts or locations in the brain can activate the alarm system.
4	The body's own pain inhibitors	Substances released due to an alarm signal are very useful in the short term. However, the condition persists, other systems are affected in unfavorable ways. The removal of a trigger, in turn, releases the body's own pain-inhibiting substances.
5	Pain memory	The autonomic nervous system, the endocrine system and the immune system consolidate a pain memory. The pain memory is not rigid, it can be changed and unfavorable patterns can be revised.
6	Pain Management	Numerous treatment methods can reduce increased nervous system sensitivity and positively affect pain and quality of life. Thoughts, cognitions and positive emotions can calm the overexcited alarm system just as well as medication. Pain is influenced by thoughts and beliefs, activity, sleep hygiene or stress, among other things.

Outcome measures

Primary outcome measures were headache frequency (days/month), migraine frequency (headache days with exclusively migraine features), both measured by a diary, and migraine associated disability score (MIDAS) (44 –46). Headache frequency includes headache days with and without migraine features in the last month.

Secondary outcome measures included migraine-specific quality of life (MSQoL) (47), depression symptoms (Patient Health Questionnaire-9 [PHQ-9]) (48), neck pain associated disability (NDI) (49), cutaneous allodynia (ASC-12) (50), as well as the acquired knowledge on the neurophysiology of pain, measured through the Neurophysiology of Pain Questionnaire (NPQ) (51 –53). Eight additional questions were formulated in order to assess the acquired specific knowledge about neck and migraine (“migraine quiz”) (Table 2). Patients additionally filled out a questionnaire on demographic data.

Table 2.

Migraine and neck pain physiology questions (“migraine quiz”).

	Correct	Wrong	Don't know
1. Migraine is a vascular disease.
2. The brain itself can cause pain because it has many sensitive nerves.
3. Migraine is now thought to be a disease of the central nervous system.
4. Triggers such as chocolate and red wine should be avoided if possible, because they can provoke a migraine attack.
5. The thought of a headache is enough to trigger it.
6. Migraine attacks are caused by tension in the neck.
7. CGRP is a hormone that only plays a role in inflammatory reactions in the brain.
8. In chronic neck pain, the representative field in the brain intended for the neck becomes blurred (the virtual body/homunculus).

Headache and neck pain frequency (days/month) and medication intake (number/month) were documented in a diary during a prolonged baseline period (T0) three months before the beginning of the intervention in order to provide more reliable pre-post estimations for the effect of physiotherapy. All measurements were taken at baseline (T1), post-treatment (T2) (immediately after the sixth intervention) and at a follow-up three months after treatment (T3). Thus, the primary outcome headache frequency was recorded four times (always referring to the previous month). All secondary outcomes were assessed three times, except for the MIDAS that has a recall time of three months. Therefore, it was analyzed just at T1 and T3 due to the overlap at T2. All variables, including baseline physical examination, were collected before randomization. At the following time points, the participants and the investigator were not blinded to the group.

At T2 and T3, patients were additionally asked to fill out the global rating of change scale (GROC) (54) to assess their subjective perception of improvement regarding three different aspects: headache days, neck pain days and quality of life. The 15-point GROC scale ranged from −7 (very much worse) to +7 (maximally improved).

Statistical methods

An a priori sample size calculation was performed for the primary outcome measure headache days, based on existing clinical studies in migraine (55,56), assuming a difference in the headache frequency between groups with an effect size of d = 0.25, a power of 80% and an alpha level of 0.05. The total required sample size was 74 patients. After accounting for 10% expected dropouts, 82 patients were recruited.

The descriptive statistics consisted of patients’ characteristics at baseline, which were presented as means and SD or frequencies and percentages for each group. Differences between groups at baseline were compared by independent samples t‐test and x² or Fisher exact test, according to the nature of the variable.

To assess if PNE has a positive influence on migraine, a two-tailed repeated measures analysis of variance (ANOVA) was used to assess between- and within-subjects factors (within: three time points, between: two intervention groups) and interactions. The achieved effect size was calculated using the F-value of the analyses of variance (57). In cases of sphericity violation (Mauchly’s test p < 0.05), values were corrected by using the Greenhouse-Geisser estimates. For the variables that exhibited baseline significant differences between the two intervention groups, baseline values were used as covariates in the model. Post-hoc pairwise comparisons were Bonferroni-corrected for multiple testing. Results were described using mean, mean difference and 95% Confidence Intervals (95%CI).

The Mann-Whitney test was used to compare groups regarding the perceived improvement of headache, neck pain and quality of life measured with the GROC scales at the timepoints T2 and T3.

Pearson’s correlations were calculated to assess the association between change in the primary outcomes and neuroscience and migraine quiz scores.

Intention to treat was employed in the analysis (all randomized subjects were analyzed) and the five missing values at post-treatment and follow-up timepoints were replaced by simple imputation.

All statistical analyses were performed at a significance level of 5% using IBM SPSS Statistics, version 26.0, by a researcher (GFC) blinded to the group allocation.

Results

Between March 2020 and August 2021, 84 subjects were recruited. Two persons were excluded before randomization, since they did not fulfil the migraine criteria defined by the ICHD-III (23). Figure 1 shows the progression of study participants within the RCT. The unequal group size arose by chance, since no block randomization was performed. Each participant selected one of two sealed envelopes.

Figure 1.

CONSORT flow diagram: progression of study participants within this RCT (enrollment, intervention assignment, follow-up, and evaluation) (38) and measurement timepoints.

Patient characteristics

Most participants (45 +/− 12 years, 94% female) reported severe impairment due to headaches accompanied by mild to moderate depressive symptoms and had neck pain on nearly half of the days per month, with mostly moderate neck associated disability (Table 3). Headache frequency, migraine frequency and neck pain intensity differed between groups at baseline. Comparison between T0 and T1 showed no changes over time for either group in terms of headaches, migraine days and medication intake. The frequency of neck pain increased in both groups from T0 to T1, however no between-group difference was observed (Table 4).

Table 3.

Baseline demographic and clinical characteristics measured at baseline (T1).

	Physiotherapy (n = 35)	Physiotherapy + PNE (n = 47)	Between-group differences
Age (years)	44.4 (12.9)	45.0 (12.5)	t = −0.23, p = 0.82
Sex (% female)	94%	94%	p = 0.64Fisher's exact test
BMI (kg/cm³)
Underweight	46%	33%	X² = 2.55, p = 0.47
Normal weight	46%	49%
Overweight	6%	16%
Obesity	3%	2%
Self-rated physical activity
Sedentary	11%	9%	X² = 2.08, p = 0.56
Active	29%	40%
Very active	51%	38%
Extremely active	9%	13%
Migraine onset (years)	25.0 (14)	24.0 (14)	t = 0.62, p = 0.54
Headache frequency (days/month)	12.9 (7.9)	8.6 (3.8)	t = 3.24, p = 0.002
Migraine frequency (days/month)	8.7 (5.7)	6.2 (3.5)	t = 2.49, p = 0.015
Migraine Intensity (VAS 0–10)
Mild (1–4)	0%	9%	X²⁼3.93, p = 0.14
Moderate (5–7)	66%	51%
Severe (8–10)	34%	40%
Use of prophylactic medication (%)	26%	19%	X² = 0.50, p = 0.32
Medication class
Betablockers	3%	11%	X²⁼12.16, p = 0.14
Anticonvulsants	3%	0%
Antidepressants	0%	6%
Monoclonal antibodies	6%	2%
Botox	6%	0%
Combination of prophylactic medications	12%	2%
Use of acute medication (amount in 1 month)	5.7 (3.6)	5.9 (3.8)	t = −0.23, p = 0.81
Midas score (0 little/no – 21 + severe impairment)	47.2 (59.3)	46.4 (62.5)	t = 0.01, p = 0.99
MSQoL score (0 never/rarely – 70 always restricted)	33.3 (13.1)	35.6 (12.9)	t = −0.77, p = 0.44
PhQ-9 score (0 minimal – 27 severe depressive symptoms)	10.8 (5.2)	9.3 (4.7)	t = 1.38, p = 0.17
Neck pain frequency (days in the last month)	14.9 (15.1)	11.7 (9.9)	t = 1.20, p = 0.23
Neck pain intensity (VAS 0–10)	6.46 (1.63)	5.25 (2.30)	t = 2.64, p = 0.01
NDI score (0 no – >34 complete impairment)	17.1 (7.1)	14.1 (7.5)	t = 1.83, p = 0.07
ASC-12 score (0 no – >9 severe allodynia)	3.7 (4.3)	3.5 (3.6)	t = 0.25, p = 0.80
Previous contact with education (neurologists)	89%	100%	p = 0.03Fisher's exact test
Neurophysiology of Pain Quiz (0–12)	6.3 (1.9)	5.5 (2.3)	t = 1.73, p = 0.09
Migraine quiz (0–8)	2.1 (1.0)	1.9 (1.3)	t = 0.90, p = 0.37

Bold indicates significant p values.ASC-12, Allodynia symptom checklist; BMI, body mass index; Midas, Migraine Disability Assessment Scale; MSQo, Migraine Specific Quality of Life; NDI, Neck disability index; PhQ-9, Patient health Questionnaire; PNE, pain neuroscience education; VAS, visual analog scale.

Table 4.

Extended baseline comparisons of the outcomes which are measured three month and directly before the beginning of the interventions including within and between-group differences.

Outcome	Group	T0 mean (95% CI)	T1 mean (95% CI)	Within-group differences (time effect)	Between-group differences (interaction time * group)
Headache frequency (days/month)	Physiotherapy	13.1 (11.3 to 14.9)	12.9 (10.9 to 14.9)	F_1,80 = 0.03, p = 0.862, ηp^2 =0.00	F_1,80 =0.78, p = 0.379, ηp^2 =0.10
Headache frequency (days/month)	Physiotherapy + PNE	8.3 (6.7 to 9.8)	8.6 (6.8 to 10.3)	F_1,80 = 0.03, p = 0.862, ηp^2 =0.00	F_1,80 =0.78, p = 0.379, ηp^2 =0.10
Migraine frequency (days/month)	Physiotherapy	9.4 (8.0 to 10.8)	8.7 (7.2 to 10.3)	F_1,80 = 0.72, p = 0.399, ηp^2 =0.009	F_1,80 =2.39, p = 0.126, ηp^2 =0.029
Migraine frequency (days/month)	Physiotherapy + PNE	6.0 (4.8 to 7.2)	6.2 (4.9 to 7.5)	F_1,80 = 0.72, p = 0.399, ηp^2 =0.009	F_1,80 =2.39, p = 0.126, ηp^2 =0.029
Analgesics intake (amount/month)	Physiotherapy	6.4 (5.2 to 7.6)	5.7 (4.5 to 7.0)	F_1,80 =1.49, p = 0.225, ηp^2 =0.18	F_1,80 =1.32, p = 0.254, ηp^2 =0.16
Analgesics intake (amount/month)	Physiotherapy + PNE	6.0 (4.9 to 7.0)	5.9 (4.9 to 7.0)	F_1,80 =1.49, p = 0.225, ηp^2 =0.18	F_1,80 =1.32, p = 0.254, ηp^2 =0.16
Neck pain frequency (days/month)	Physiotherapy	12.1 (9.1 to 15.1)	14.9 (10.8 to 19.1)	F_1,80 = 7.44, p = 0.008, ηp^2 =0.085	F_1,80 =0.50, p = 0.481, ηp^2 =0.006
Neck pain frequency (days/month)	Physiotherapy + PNE	10.0 (7.4 to 12.5)	11.7 (8.1 to 15.3)	F_1,80 = 7.44, p = 0.008, ηp^2 =0.085	F_1,80 =0.50, p = 0.481, ηp^2 =0.006

Bold indicates significant p values.ηp², partial eta square; PNE, pain neuroscience education.

Primary outcomes

Headache days significantly decreased at post-treatment and at follow-up in the total sample (F_2,158 = 4.12, p = 0.02) as compared to the prolonged baseline T0 as well as baseline T1 with a small effect size (d = 0.46). Headache days in the PT group significantly decreased by 1.93 days (95%CI: 0.07 to 3.78, p = 0.039) at follow-up but not at post-treatment (mean difference: 0.77, 95%CI: −0.75 to 2.29, p = 0.664). The PT + PNE group also showed a significant reduction of 3.48 days (95%CI: 1.89 to 5.06) at follow-up, but not at post-treatment (mean difference: 1.25, 95%CI: −0.05 to 2.55, p = 0.039). No interaction between group and time was observed for headache frequency (F_2,158 = 1.35, p = 0.26, d = 0.26).

When exclusively assessing migraine days per month, there was also an effect of time within both groups (F_2,158 = 4.79, p = 0.01) with a medium effect size (d = 0.5). A significant interaction between group*time was observed (F_2,158 = 5.04, p = 0.008), with the PT + PNE group showing a larger reduction of migraine frequency (mean effect size d = 0.51). Compared to baseline migraine days within the PT group did not present a significant reduction neither at post-treatment (mean difference: 0.16, 95%CI: −0.93 to 1.26, p = 1.00) nor at follow-up (mean difference: 0.99, 95%CI: −0.25 to 2.24, p = 0.163). The PT + PNE group presented a reduction of 1.28 migraine days (95%CI: 0.34 to 2.22, p = 0.004) at post-treatment and 3.05 days (95%CI: 1.98 to 5.06, p < 0.0001) at follow-up, in contrast to baseline (Table 5, Figure 2). In comparison to the PT group, the PT + PNE presented a significant reduction of 2.06 migraine days at follow-up (95%CI: 0.70 to 3.42, p = 0.003), but not at post-treatment (mean difference: 1.12, 95%CI: −0.07 to 2.31, p = 0.066).

Table 5.

Means (95% CIs) at baseline, post-treatment, and follow-up for all outcomes and interactions of group and time including effect sizes (d).

Outcome	Group	Baseline mean (95% CI)	Post-treatment, mean (95% CI)	Follow-up mean (95% CI)	Within-group differences (time effect) (d)	Between-group differences (interaction time*group) (d)
Headache frequency (days/month)	Physiotherapy	12.9 (10.0 to 15.5)	11.4 (9.0 to 13.9)	9.7 (7.6 to 11.8)	F_2,158 = 4.12,p = 0.02 (d = 0.46)	F_2,158 = 1.35, p = 0.26 (d = 0.26)
Headache frequency (days/month)	Physiotherapy + PNE	8.6 (7.4 to 9.7)	7.8 (6.7 to 8.9)	6.0 (4.9 to 7.2)	F_2,158 = 4.12,p = 0.02 (d = 0.46)	F_2,158 = 1.35, p = 0.26 (d = 0.26)
Migraine frequency (days/month)	Physiotherapy	8.8 (6.9 to 10.6)	8.1 (6.4 to 9.8)	7.1 (5.4 to 8.7)	F_2,158 = 4.79, p = 0.01(d = 0.5)	F_2,158 = 5.04, p = 0.008 (d = 0.51)
Migraine frequency (days/month)	Physiotherapy + PNE	6.2 (5.2 to 7.2)	5.3 (4.5 to 6.1) ^†	3.7 (2.9 to 4.4)*^†	F_2,158 = 4.79, p = 0.01(d = 0.5)	F_2,158 = 5.04, p = 0.008 (d = 0.51)
Analgesic intake (number/month)	Physiotherapy	5.8 (4.4 to 6.9)	5.66 (4.54 to 6.77)	4.83 (3.57 to 6.09)	F_2,160 = 5.77, p = 0.004(d = 0.56)	F_2,160 = 0.25, p = 0.77 (d = 0.12)
Analgesic intake (number/month)	Physiotherapy + PNE	5.9 (4.9 to 7.0)	5.4 (4.3 to 6.4)	4.5 (3.4 to 5.6)	F_2,160 = 5.77, p = 0.004(d = 0.56)	F_2,160 = 0.25, p = 0.77 (d = 0.12)
Neck pain frequency (days/month)	Physiotherapy	14.9 (10.80 to 19.14)	12.99 (9.92 to 16.07)	14.91 (10.09 to 19.14)	F_2,160 = 1.39, p = 0.24(d = 0.26)	F_2,160 = 0.98, p = 0.38 (d = 0.22)
Neck pain frequency (days/month)	Physiotherapy + PNE	11.7 (8.1 to 15.3)	9.1 (6.3 to 11.6)	7.6 (3.6 to 11.9)	F_2,160 = 1.39, p = 0.24(d = 0.26)	F_2,160 = 0.98, p = 0.38 (d = 0.22)
Neck pain intensity (VAS)	Physiotherapy	6.4 (5.9 to 7.0)	5.1 (4.6 to 5.6)	5.1 (4.4 to 5.7)	F_2,158 = 6.58, p = 0.002(d = 0.6)	F_2,158 = 0.09, p = 0.91 (d = 0.07)
Neck pain intensity (VAS)	Physiotherapy + PNE	5.2 (4.6 to 5.9)	4.4 (3.7 to 5.1)	4.4 (3.8 to 5.0)	F_2,158 = 6.58, p = 0.002(d = 0.6)	F_2,158 = 0.09, p = 0.91 (d = 0.07)
Neck disability index (Score)	Physiotherapy	17.1 (14.5 to 19.4)	12.0 (9.6 to 14.4)	12.5 (10.3 to 15.0)	F_2,160 =30.14, p < 0.001(d = 1.27)	F_2,160 = 1.87, p = 0.15 (d = 0.46)
Neck disability index (Score)	Physiotherapy + PNE	13.7 (11.7 to 15.8)	10.8 (8.8 to 12.8)	10.8 (8.9 to 13.0)	F_2,160 =30.14, p < 0.001(d = 1.27)	F_2,160 = 1.87, p = 0.15 (d = 0.46)
ASC-12 (Score)	Physiotherapy	3.7 (2.4 to 5.0)	1.8 (0.9 to 3.0)	2.2 (1.0 to 3.4)	F_2,160 = 8.82, p = 0.001(d = 0.68)	F_2,160 = 1.38, p = 0.25 (d = 0.26)
ASC-12 (Score)	Physiotherapy + PNE	3.5 (2.2 to 4.5)	2.6 (1.7 to 3.5)	2.6 (1.6 to 3.8)	F_2,160 = 8.82, p = 0.001(d = 0.68)	F_2,160 = 1.38, p = 0.25 (d = 0.26)
PHQ-9 (Score)	Physiotherapy	10.7 (9.2 to 12.5)	8.6 (6.9 to 10.3)	7.9 (6.3 to 9.5)	F_2,160 = 26.86, p < 0.001(d = 1.21)	F_2,160 = 0.11, p = 0.90 (d = 0.06)
PHQ-9 (Score)	Physiotherapy + PNE	9.2 (7.8 to 10.6)	7.0 (5.4 to 8.5)	6.5 (5.3 to 8.0)	F_2,160 = 26.86, p < 0.001(d = 1.21)	F_2,160 = 0.11, p = 0.90 (d = 0.06)
MIDAS (Score)	Physiotherapy	47.2 (29.2 to 65.2)	–	28.0 (16.4 to 39.6)	F_1,80 = 24.08, p < 0.001 (d = 1.15)	F_1,80 = 0.30, p = 0.583 (d = 0.13)
MIDAS (Score)	Physiotherapy + PNE	46.4 (30.9 to 61.9)	–	22.4 (12.3 to 32.4)	F_1,80 = 24.08, p < 0.001 (d = 1.15)	F_1,80 = 0.30, p = 0.583 (d = 0.13)
MSQoL (Score)	Physiotherapy	33.3 (28.9 to 37.6)	25.3 (20.4 to 30.4)	25.3 (19.6 to 30.8)	F_2,160 = 38.50, p < 0.001(d = 1.45)	F_2,160 = 1.76, p = 0.175 (d = 0.31)
MSQoL (Score)	Physiotherapy + PNE	35.6 (31.7 to 39.4)	24.9 (20.5 to 29.0)	22.6 (17.8 to 27.4)	F_2,160 = 38.50, p < 0.001(d = 1.45)	F_2,160 = 1.76, p = 0.175 (d = 0.31)
Neurophysiology of Pain Quiz (Score)	Physiotherapy	6.3 (5.6 to 6.9)	6.7 (6.3 to 7.2)	6.7 (6.2 to 7.2)	F_2,160 = 88.46, p < 0.001(d = 2.18)	F_2,160 = 52.29,p < 0.001 (d = 1.69)
Neurophysiology of Pain Quiz (Score)	Physiotherapy + PNE	5.5 (4.9 to 6.1)	9.8 (9.4 to 10.2)*^†	9.5 (9.0 to 9.9)*^†	F_2,160 = 88.46, p < 0.001(d = 2.18)	F_2,160 = 52.29,p < 0.001 (d = 1.69)
Migraine quiz (Score)	Physiotherapy	2.1 (1.7 to 2.5)	2.6 (2.2 to 3.2)^†	3.0 (2.5 to 3.5)^†	F_2,160 = 84.83, p < 0.001 (d = 2.15)	F_2,160 = 28.39, p < 0.001 (d = 1.23)
Migraine quiz (Score)	Physiotherapy + PNE	1.9 (1.4 to 2.2)	4.6 (4.4 to 5.0)*^†	4.5 (4.2 to 5.1)*^†	F_2,160 = 84.83, p < 0.001 (d = 2.15)	F_2,160 = 28.39, p < 0.001 (d = 1.23)

Bold indicates significant results.Mean values of all outcomes at three time points. Superiority of the combination of PT + PNE is shown for migraine days and the neurophysiology of pain quiz. *p < 0.05, Physiotherapy versus Physiotherapy + PNE. ^†p < 0.01 within-group differences versus baseline. Effect size d = <0.2 no effect; 0.2–0.4 small effect; 0.5–0.7 medium effect; >0.8 large effect.

ASC-12, Allodynia symptom checklist; Midas, Migraine Disability Assessment Scale; MSQoL, Migraine Specific Quality of Life; NDI, Neck disability index; PhQ-9, Patient health Questionnaire; PNE, pain neuroscience education; VAS, visual analog scale.

Figure 2.

Mean and 95% confidence intervals of headache frequency and migraine frequency among groups at baseline, post-treatment and 3-month follow-up. Both groups improved over time and a significant difference between groups was found with the PT+PNE group showing a larger reduction of migraine frequency (^†p < 0.01 within-group differences versus baseline. *Between-group differences p = 0.008. **Estimated values adjusted by the baseline).

Migraine-related disability (MIDAS) significantly decreased at follow-up in the total sample (F_1,80 = 24.08, p < 0.001) as compared to baseline T1 with a large effect size (d = 1.15). The MIDAS in the PT group significantly decreased 28.0 points (95% CI: 16.4 to 39.6) at follow-up, the MIDAS in PT + PNE group significantly decreased 22.4 points (95% CI: 12.3 to 32.4)). No interaction between group and time was observed for MIDAS scores (F_1,80 = 0.30, p = 0.583, d = 0.13).

Secondary outcomes

Results of secondary outcomes (medication intake [number/month], neck pain intensity [VAS], neck pain frequency, Neck disability index [NDI], Allodynia symptom checklist [ASC-12], Patient health Questionnaire [PHQ-9], Migraine Specific Quality of Life [MSQoL]), demonstrated a significant effect of time for each of these outcomes, with no interaction between time and group (Table 5).

A moderate and significant correlation was observed between the reduction of headache days at post-treatment and changes in the “migraine quiz” (r = 0.52, p < 0.0001). Weak and non-significant correlations were observed between the changes in NPQ and reduction of headache days at post-treatment (r = 0.10, p = 0.36), reduction of migraine frequency post-treatment (r = 0.10, p = 0.372), and changes in the “migraine quiz” (r = 0.03, p = 0.79). Both groups rated the GROC questions on headache, neck pain and quality of life similarly. Mean improvements ranged between +2.0 and +3.0 points post treatment and at three-month follow-up (Table 6).

Table 6.

Patients’ perception of change post treatment and at three-month follow-up according to GROC scales.

	Physiotherapy (n = 35) (Mean, SD)	Physiotherapy + PNE (n = 47) (Mean, SD)	Between group difference (U-test)
Headache post treatment	2.5 (1.8)	2.6 (1.5)	U = 868.00, p = 0.666
Headache follow up	2.4 (1.7)	2.9 (2.3)	U = 930.00, p = 0.309
Neck pain post treatment	2.9 (1.6)	2.6 (1.9)	U = 720.00, p = 0.331
Neck pain follow up	2.0 (2.1)	2.3 (2.2)	U = 891.50, p = 0.514
Quality of life post treatment	2.5 (2.2)	3.0 (1.7)	U = 924.00, p = 0.337
Quality of life follow up	2.2 (2.0)	2.7 (2.3)	U = 970.00, p = 0.161

GROC, Global rating of change.

No harmful or adverse events were observed during the study.

Discussion

This study is the first to investigate additional effects of PNE to physiotherapy in patients with migraine. While the interaction of time and group was not statistically significant for the reduction of headache frequency and MIDAS, there was a trend towards better outcomes in favor of PNE for the primary endpoints just mentioned, especially at follow-up. The MIDAS showed in both groups high scores at baseline. A score >21 is considered a severe impairment. The ANOVA showed a significant effect of time at three-month follow-up for both groups (within-group differences p = 0.001) but a between groups difference for MIDAS scores was not observed evaluating the interaction of time and group. A change of 4.5 points or more in four weeks (for three months = 13.5 points) represents a clinically significant change for patients with frequent episodic and chronic migraine (58). Improvement values at follow-up were far above this minimally important change cut-off in both groups with a strong effect size (d = 1.15). An improvement of more than 50% was only measured in the PT + PNE group (Table 5).

The analysis further showed that combining physiotherapy with PNE was superior to physiotherapy alone, by significantly decreasing migraine days by about three per month. A similar but not significant direction was seen in the secondary outcomes and in patients' perceptions of change; in five of six categories, patients in the PT + PNE group reported a greater positive change. Specifically, the variable “migraine days/month” is addressed by the PNE and the neurophysiology of chronic pain. Therefore, we attribute the results to the additional intervention. It is certainly worth discussing that the PT + PNE group received more therapy overall and the combination of two different treatment approaches can generally lead to better results, but the additional treatment should otherwise have affected the other variables as well. Furthermore, we aimed to specifically investigate if adding an intervention that is standard care for other chronic pain conditions, would provide an additional benefit for migraine patients.

Learning the underlying neurophysiology of pain seemed to have effectively enhanced the patients’ understanding of their disease, as shown by the improvement in the neurophysiology of pain and migraine quiz. Furthermore, the correlation between the migraine quiz results and headache frequency improvement might be explained by reduced migraine-related fear and modified pain cognitions. In other pain conditions, this has been reported to evoke a “desensitization of overactive alarm systems” and brain areas involved in pain (43,59) and positively influenced emotions and thoughts (37). The one-to-one setting used in this current study allowed to take into account the individual behavioral, psychological, and environmental factors that may contribute to a specific patient’s pain experience and persistence.

Interestingly, almost 100% of the participants stated that they had already received education on migraine, which consisted of information about the disease. However, none of the patients had received any information about the neurophysiology of pain, which is specifically addressed in the pain neuroscience education intervention, applied in this current study. Previous research on the influence of education on migraine focused on lifestyle factors such as sleep and eating behavior, stress reduction, relaxation, trigger management and medication use (36,60). A result of 60% correct answers in the Neurophysiology of Pain Quiz is deemed to indicate successful participation in PNE (52). As expected, only the PT + PNE group (79% correct answers vs 55% in the PT group) improved their knowledge on the neurophysiology of pain.

Some concepts within the classical PNE – primarily designed for patients with low back pain or osteoarthritis – cannot be intuitively transferred to migraine, therefore contents had to be adapted. A moderate and significant correlation was found between the reduction of headache days after treatment and migraine-specific knowledge, mapped in the migraine quiz. The current data provides first evidence that comprehensive information on migraine as a chronic pain disease may help desensitize the “overactive alarm systems” in this population. Migraine patients reported fear of attacks as an important indicator of improvement after non-pharmacological interventions (45). A better understanding of the disease and its underlying pathophysiology may facilitate a reduction of this fear of the next attack.

Significant superiority of the PT + PNE combination was shown in the analysis of migraine days per month, which is in line with results for combined PNE and physiotherapy in other pain syndromes (61,62), also shown to be effective to reduce chronic neck pain (63). Considering that up to 80% of migraine patients complain about neck pain (3) and that neck dysfunctions were detected in almost all migraine patients (12), an examination of the neck and a treatment approach addressing identified neck dysfunctions or even chronic neck pain, should be a routine procedure in migraine management.

Previous research highlighted the added value of combining PT with PNE (37,64,65), therefore this approach was chosen for the current study. The reasoning behind this combination was to modify pain “bottom-up” (by reducing nociceptive afferents) as well as “top-down” through PNE (activating endogenous pain modulation) (66).

The PT + PNE group had a reduction in neck pain days at follow-up which was not observed in the PT group. This indicates that understanding the pathophysiology strengthens self-efficacy (41), an effect previously demonstrated for other chronic pain conditions following PNE (37,65).

Limitations

A limitation of this study is the absence of a control group that did not receive an intervention to more specifically assess the effect of physical therapy. We used an extended baseline in order to provide more reliable pre-post estimations for the effect of physiotherapy. Taking into consideration the three months of baseline data, the current study allows us to estimate the effect of physiotherapy in migraine. However, this needs to be confirmed by future studies in a randomized controlled design.

Secondary outcome measures indicated that physiotherapy can reduce acute medication intake, neck pain intensity and neck associated disability as well as allodynia, depression, migraine associated disability and that it improved the disease-related quality of life. However, the study design without a control or placebo group did not allow reasoned recommendation regarding the efficacy of additional PNE rather than for the efficacy of physiotherapy alone. Furthermore, the combination of two different treatment approaches can generally lead to better results. In this way we recommend that future studies consider the addition of a "sham-PNE" intervention, which would complement the findings of the current study.

The effect of the intervention was only assessed at a three-month follow-up, thus future studies are necessary to study long-term effects. Previous research on PNE showed that effects stabilized or even increased over time (63).

Conclusion

This study is the first to describe and apply a structured PNE curriculum in a migraine population. Both groups, physiotherapy or physiotherapy + PNE, showed improvement of primary and secondary outcomes data over time. Physiotherapy in combination with PNE was superior to physiotherapy alone regarding the reduction of migraine frequency. More stringent RCTs are needed to improve the strength of the evidence. Physiotherapy should be considered for the treatment of migraine patients and accompanied by education on the neurophysiology of pain.

Article highlights

Migraine patients receiving either physiotherapy or physiotherapy + pain neuroscience education showed improvements in the primary and secondary outcomes after the intervention.

Physiotherapy combined with pain neuroscience education was more effective than physiotherapy alone to reduce migraine frequency.

Physiotherapy also accompanied by pain neuroscience education can be considered for the treatment of migraine.

Footnotes

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: A funding source by the Friedrich-Ebert-Stiftung, doctoral funding, Godesberger Allee 149, 53175 Bonn was received by the corresponding author RM.

Other information

The trial is registered at the German Clinical Trials Register (Deutsches Register Klinischer Studien) (DRKS00020804), accessible at: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00020804 All the datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

ORCID iDs

Gabriela Ferreira Carvalho

Kerstin Luedtke

References

Goadsby

Holland

PR.

An update: Pathophysiology of migraine. Neurol Clin 2019; 37: 651–671.

May

Understanding migraine as a cycling brain syndrome: reviewing the evidence from functional imaging. Neurol Sci 2017; 38: 125–130.

Ashina

Bendtsen

Lyngberg

, et al. Prevalence of neck pain in migraine and tension-type headache: a population study. Cephalalgia 2015; 35: 211–219.

Calhoun

Ford

Millen

, et al. The prevalence of neck pain in migraine. Headache 2010; 50: 1273–1277.

Anarte-Lazo

Carvalho

Schwarz

, et al. Differentiating migraine, cervicogenic headache and asymptomatic individuals based on physical examination findings: a systematic review and meta-analysis. BMC Musculoskelet Disord 2021; 22: 755.

Carvalho

Schwarz

Szikszay

, et al. Physical therapy and migraine: musculoskeletal and balance dysfunctions and their relevance for clinical practice. Braz J Phys Ther 2020; 24: 306–317.

Meise

Lüdtke

Probst

, et al. Zervikaler “joint position error” bei Kopfschmerzen- Systematische Literaturübersicht und empirische Daten bei chronischer Migräne. Der Schmerz 2019; 33: 204–211.

Oliveira-Souza

AIS

Florencio

Carvalho

, et al. Reduced flexion rotation test in women with chronic and episodic migraine. Braz J Phys Ther 2019; 23: 387–394.

Szikszay

Luedtke

Harry von

Increased mechanosensivity of the greater occipital nerve in subjects with side-dominant head and neck pain – a diagnostic case-control study. J Man Manip Ther 2018; 26: 237–248.

10.

Bragatto

Bevilaqua-Grossi

Benatto

, et al. Is the presence of neck pain associated with more severe clinical presentation in patients with migraine? A cross-sectional study. Cephalalgia 2019; 39: 1500–1508.

11.

Özer

Benlier

Neck pain: is it part of a migraine attack or a trigger before a migraine attack?

Acta Neurol Belg 2020; 120: 289–293.

12.

Luedtke

Starke

May

Musculoskeletal dysfunction in migraine patients. Cephalalgia 2018; 38: 865–875.

13.

Luedtke

May

Stratifying migraine patients based on dynamic pain provocation over the upper cervical spine. J Headache Pain 2017; 18: 97.

14.

Watson

Drummond

PD.

Head pain referral during examination of the neck in migraine and tension-type headache. Headache 2012; 52: 1226–1135.

15.

Watson

Drummond

PD.

Cervical referral of head pain in migraineurs: effects on the nociceptive blink reflex. Headache 2014; 54: 1035–1045.

16.

Bartsch

Goadsby

PJ.

The trigeminocervical complex and migraine: Current concepts and synthesis. Curr Pain Headache Rep 2003; 7: 371–376.

17.

Basedau

Nielsen

Asmussen

, et al. Experimental evidence of a functional relationship within the brainstem trigeminocervical complex in humans. Pain 2022; 163: 729–734.

18.

Falsiroli Maistrello

Rafanelli

Turolla

(2019). Manual therapy and quality of life in people with headache: systematic review and meta-analysis of randomized controlled trials. Curr Pain Headache Rep 2019; 23: 78.

19.

Luedtke

Starke

von Korn

, et al. (2020) Neck treatment compared to aerobic exercise in migraine: A preference-based clinical trial. Cephalalgia Reports 2020; 3: 251581632093068

20.

Andreou

Edvinsson

Mechanisms of migraine as a chronic evolutive condition. J Headache Pain 2019; 20: 117.

21.

Chronic migraine: A process of dysmodulation and sensitization. Mol Pain 2018; 14: 1744806918767697.

22.

Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd Edition. Cephalalgia 2018; 38: 1–211.

23.

Treede

Rief

Barke

, et al. Chronic pain as a symptom or a disease: the IASP Classification of Chronic Pain for the International Classification of Diseases (ICD-11). Pain 2019; 160: 19–27.

24.

Di Antonio

Castaldo

Ponzano

, et al. Trigeminal and cervical sensitization during the four phases of the migraine cycle in patients with episodic migraine. Headache 2022; 62: 176–190.

25.

Mungoven

Henderson

Meylakh

Chronic migraine pathophysiology and treatment: a review of current perspectives. Front Pain Res 2021; 2: 705276.

26.

Luedtke

Adamczyk

Mehrtens

, et al. Upper cervical two-point discrimination thresholds in migraine patients and headache-free controls. J Headache Pain 2018; 19: 47.

27.

Nahman-Averbuch

Shefi

Schneider

2nd , et al. Quantitative sensory testing in patients with migraine: a systematic review and meta-analysis. Pain 2018; 159: 1202–1223.

28.

Szikszay

Adamczyk

Carvalho

, et al. Offset analgesia: somatotopic endogenous pain modulation in migraine. Pain 2020; 161: 557–564.

29.

Pancheri

Maraone

Roselli

, et al. The role of stress and psychiatric comorbidities as targets of non-pharmacological therapeutic approaches for migraine. Riv Psichiatr 2020; 55: 262–268.

30.

Tiseo

Vacca

Felbush

, et al. Migraine and sleep disorders: a systematic review. J Headache Pain 2020; 21: 126.

31.

Szabo

Green

Karunakaran

, et al. Migraine: Interactions between brain’s trait and state. CNS Spectrums 2022; 27: 561–569.

32.

National Institute for Health and Care Excellence. Chronic pain (primary and secondary) in over 16s: assessment of all chronic pain and management of chronic primary pain. (NICE Guideline, No. 193.), https://www.ncbi.nlm.nih.gov/books/NBK569960/ (accessed 7 April 2021).

33.

Barbari

Storari

Maselli

, et al. Applicability of pain neuroscience education: Where are we now? J Back Musculoskelet Rehabil 2021; 34: 511–520.

34.

Moseley

Butler

DS.

Fifteen years of explaining pain: the past, present, and future. J Pain 2015; 16: 807–813.

35.

Wijma

van Wilgen

Meeus

, et al. Clinical biopsychosocial physiotherapy assessment of patients with chronic pain: The first step in pain neuroscience education. Physiother Theory Pract 2016; 32: 368–384.

36.

Kindelan-Calvo

Gil-Martínez

Paris-Alemany

, et al. Effectiveness of therapeutic patient education for adults with migraine. A systematic review and meta-analysis of randomized controlled trials. Pain Med 2014; 15: 1619–1636.

37.

Minen

Kaplan

Akter

, et al. Neuroscience education as therapy for migraine and overlapping pain conditions: a scoping review. Pain Med 2021; 22: 2366–2383.

38.

Moher

Hopewell

Schulz

, et al. CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. Int J Surg 2012; 10: 28–55.

39.

Luedtke

Boissonnault

Caspersen

, et al. International consensus on the most useful physical examination tests used by physiotherapists for patients with headache: A Delphi study. Man Ther 2016; 23: 17–24.

40.

Butler

Moseley

LG.

Schmerzen Verstehen. Berlin-Heidelberg: Springer Verlag, 2016.

41.

Louw

Puentedura

Therapeutic Neuroscience Education: Teaching Patients about Pain: A Guide for Clinicians. First Edition. United States: International Spine and Pain Institute, 2013.

42.

Louw

Puentedura

Zimney

Teaching patients about pain: It works, but what should we call it?

Physiother Theory Pract 2016; 32: 325–331.

43.

Moseley

Butler

DS.

Explain Pain Supercharged. First edition. Adelaide, Australia: Noigroup Publications, 2017.

44.

Benz

Lehmann

Gantenbein

, et al. Translation, cross-cultural adaptation and reliability of the German version of the migraine disability assessment (MIDAS) questionnaire. Health Qual Life Outcomes 2018; 16: 42.

45.

Luedtke

Basener

Bedei

, et al. Outcome measures for assessing the effectiveness of non-pharmacological interventions in frequent episodic or chronic migraine: a Delphi study. BMJ Open 2020; 10: e029855.

46.

Houts

McGinley

Nishida

, et al. Systematic review of outcomes and endpoints in acute migraine clinical trials. Headache 2021; 61: 263–275.

47.

Rendas-Baum

Bloudek

Maglinte

, et al. The psychometric properties of the Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ) in chronic migraine patients. Qual Life Res 2013; 22: 1123–1133.

48.

Löwe

Unützer

Callahan

, et al. Monitoring depression outcomes with the PHQ-9. Responsiveness and reliability. Med Care 2004; 42: S1194–1201.

49.

Cramer

Lauche

Langhorst

Dobos

Michalsen

Validation of the German version of the Neck Disability Index (NDI).

BMC Musculoskelet Disord 2014; 15: 91.

50.

Lipton

Bigal

Ashina

, et al. Cutaneous allodynia in the migraine population. Ann Neurol 2008; 63: 148–158.

51.

Catley

O'Connell

Moseley

GL.

How good is the neurophysiology of pain questionnaire? A Rasch analysis of psychometric properties. J Pain 2013; 14: 818–827.

52.

Richter

Maurus

Moog

, et al. (2019). Die deutsche Version des Neurophysiology of Pain Questionnaire. Schmerz 2019; 33: 244–252.

53.

Vaughan

Mulcahy

Fitzgerald

, et al. (2019). Evaluating Patient’s Understanding of Pain Neurophysiology. Clin J Pain 2019; 35: 133–139.

54.

Kamper

Maher

Mackay

Global rating of change scales: a review of strengths and weaknesses and considerations for design. J Man Manip Ther 2009; 17: 163–170.

55.

Hedborg

Muhr

Multimodal behavioral treatment of migraine: An Internet-administered, randomized, controlled trial.

Upsala J Med Sci 2011; 116: 169–186.

56.

Lemstra

Stewart

Olszynski

WP.

Effectiveness of multidisciplinary intervention in the treatment of migraine: a randomized clinical trial. Headache 2002; 42: 845–854.

57.

Thalheimer

Cook

How to calculate effect sizes from published research: A simplified methodology. Work-Learning Res 2002; 1: 1–9.

58.

Carvalho

Luedtke

Braun

Minimal important change and responsiveness of the Migraine Disability Assessment Score (MIDAS) questionnaire. J Headache Pain 2021; 22: 126.

59.

Aguirrezabal

Pérez de San Román

Cobos-Campos

, et al. Effectiveness of a primary care-based group educational intervention in the management of patients with migraine: a randomized controlled trial. Prim Health Care Res Dev 2019; 20: e155.

60.

Sharpe

Dudeney

Williams

ACC

, et al. Psychological therapies for the prevention of migraine in adults. Cochrane Database Syst Rev 2019; 7: CD012295. [31264211]

61.

Bodes Pardo

Lluch Girbés

Roussel

, et al. Pain neurophysiology education and therapeutic exercise for patients with chronic low back pain: a single-blind randomized controlled trial. Arch Phys Med Rehabil 2018; 99: 338–347.

62.

Galan-Martin

Montero-Cuadrado

Lluch-Girbes

, et al. Pain neuroscience education and physical therapeutic exercise for patients with chronic spinal pain in Spanish physiotherapy primary care: A pragmatic randomized controlled trial. J Clin Med 2020; 9: 1201.

63.

Beltran-Alacreu

López-de-Uralde-Villanueva

Fernández-Carnero

, et al. Manual therapy, therapeutic patient education, and therapeutic exercise, an effective multimodal treatment of nonspecific chronic neck pain: a randomized controlled trial. Am J Phys Med Rehabil 2015; 94: 887–897.

64.

Louw

Zimney

Puentedura

, et al. The efficacy of pain neuroscience education on musculoskeletal pain: A systematic review of the literature. Physiother Theory Pract 2016; 32: 332–355.

65.

Louw

Nijs

Puentedura

EJ.

A clinical perspective on a pain neuroscience education approach to manual therapy. J Man Manip Ther 2017; 25: 160–168.

66.

Benedetti

Thoen

Blanchard

, et al. Pain as a reward: changing the meaning of pain from negative to positive co-activates opioid and cannabinoid systems. Pain 2013; 154: 361–367.

Additional effects of pain neuroscience education combined with physiotherapy on the headache frequency of adult patients with migraine: A randomized controlled trial

Abstract

Keywords

Introduction

Methods

Study design

Participants

Interventions

Outcome measures

Statistical methods

Results

Patient characteristics

Primary outcomes

Secondary outcomes

Discussion

Limitations

Conclusion

Article highlights

Footnotes

Declaration of conflicting interests

Funding

Other information

ORCID iDs

References