Profiling migraine patients according to clinical and psychophysical characteristics: clinical validity of distinct migraine clusters.

AIMS: Investigate if different clinical and psychophysical bedside tools can differentiate between district migraine phenotypes in ictal/perictal (cohort 1) and interictal (cohort 2) phases. METHOD: This observational study included two independent samples in which patients were subgrouped into distinct clusters using standardized bedside assessment tools (headache frequency, disability, cervical active range of motion, pressure pain threshold in different areas): (A) cohort 1-ictal/perictal migraine patients were subgrouped, based on previous studies, into two clusters, i.e., Cluster-1.1 No Psychophysical Impairments (NPI) and Cluster-1.2 Increased Pain Sensitivity and Cervical Musculoskeletal Dysfunction (IPS-CMD); (B) cohort 2-interictal migraine patients were subgrouped into three clusters, i.e., Cluster-2.1 NPI, Cluster-2.2 IPS, and Cluster-2.3 IPS-CMD. Clinical characteristics (multiple questionnaires), somatosensory function (comprehensive quantitative sensory testing (QST)), and cervical musculoskeletal impairments (cervical musculoskeletal assessment) were assessed and compared across headache clusters and a group of 56 healthy controls matched for sex and age. RESULTS: Cohort 1: A total of 156 subjects were included. Cluster-1.2 (IPS-CMD) had higher headache intensity (p = 0.048), worse headache-related (p = 0.003) and neck-related disability (p = 0.005), worse quality of life (p = 0.003), and higher symptoms related to sensitization (p = 0.001) and psychological burden (p = 0.005) vs. Cluster-1.1(NPI). Furthermore, Cluster-1.2 (IPS-CMD) had (1) reduced cervical active and passive range of motion (p < 0.023), reduced functionality of deep cervical flexors (p < 0.001), and reduced values in all QST(p < 0.001) vs. controls, and (2) reduced active mobility in flexion, left/right lateral flexion (p < 0.045), and reduced values in QST (p < 0.001) vs. Cluster-1.1 (NPI). Cohort 2: A total of 154 subjects were included. Cluster-2.3 (IPS-CMD) had (1) longer disease duration (p = 0.006), higher headache frequency (p = 0.006), disability (p < 0.001), and psychological burden (p = 0.027) vs. Cluster-2.2 (IPS) and (2) higher headache-related disability (p = 0.010), neck-related disability (p = 0.009), and higher symptoms of sensitization (p = 0.018) vs. Cluster-2.1 (NPI). Cluster-2.3(IPS-CMD) had reduced cervical active and passive range of motion (p < 0.034), and reduced functionality of deep cervical flexors (p < 0.001), vs. controls, Custer-2.1 (NPI), and Cluster-2.2 (IPS). Cluster-2.2 (IPS) and 2.3 (IPS-CMD) had reduced QST values vs. controls (p < 0.001) and Cluster-2.1 (p < 0.039). CONCLUSION: A battery of patient-related outcome measures (PROMs) and quantitative bedside tools can separate migraine clusters with different clinical characteristics, somatosensory functions, and cervical musculoskeletal impairments. This confirms the existence of distinct migraine phenotypes and emphasizes the importance of migraine phases of which the characteristics are assessed. This may have implications for responders and non-responders to anti-migraine medications.

Profiling migraine patients according to clinical and psychophysical characteristics: a cluster analysis approach.

AIM: This study aims to profile migraine patients according clinical and psychophysical characteristics. METHOD: In this observational study, two cohorts of migraine patients(episodic/chronic) were included. Cohort-1: ictal/perictal phase; Cohort-2: interictal phase.The following variables were assessed: headache frequency; disability; cervical active range of motion(AROM) in flexion, extension, right/left lateral flexion, right/left rotation; pressure-pain threshold(PPT) over: temporalis, two cervical areas(C1/C4 vertebral segments), and two distal pain-free areas(hand/leg). Cluster analysis was performed using the K-means algorithm. Differences across clusters were investigated. RESULTS: Cohort-1: 100 patients were included, and two clusters were identified. Cluster-1.1 (19%), Cluster-1.2 (81%). Cluster 1.1 had a higher percentage of men (P = .037) and higher disability (P = .003) compared to Clusters 1.2. Cluster 1.2 had reduced AROM in flexion, extension, and left/right lateral flexion (P < .037), and lower PPT value in all areas (P < .001) compared to Cluster 1.1. Cohort-2: 98 patients were included and three clusters were identified. Cluster-2.1(18%), Cluster-2.2(45%), and Cluster-2.3(37%). Cluster-2.1 had a higher percentage of men compared to clusters-2.2 and 2.3 (P = .009). Cluster-2.3 had higher headache frequency, and disability compared to Cluster-2.2 (P < .006), and higher disability compared to Cluster-2.1 (P = .010). Cluster-2.3 had reduced AROM in all directions compared to Clusters-2.1 and 2.2 (P < .029). Clusters-2.2 and 2.3 have lower PPT values in all areas compared to Cluster-1.1 (P < .001). CONCLUSION: In the Ictal/perictal phase, two clusters were identified according to clinical and psychophysical characteristics, with one group showing no psychophysical impairment and one with increased pain-sensitivity and cervical musculoskeletal-dysfunctions.In the interictal phase, three clusters could be identified, with one group showing no psychophysical impairment, one increased pain-sensitivity, and one increased pain sensitivity and cervical musculoskeletal-dysfunctions.

Trigeminocervical pain sensitivity during the migraine cycle depends on headache frequency.

OBJECTIVE: This experimental study aimed to assess pain sensitivity in low-frequency episodic migraine (LFEM), high-frequency episodic migraine (HFEM), and chronic migraine (CM) patients across the different phases of the migraine cycle. METHOD: In this observational, experimental study, clinical characteristics (diary and time from the last/next headache attack), and quantitative sensory testing (QST) (wind-up pain ratio (WUR) and pressure pain threshold (PPT) from the trigeminal area and PPT from the cervical spine) was performed. LFEM, HFEM, and CM were assessed in each of the 4 migraine phases (HFEM and LFEM: interictal, preictal, ictal, and postictal; CM: interictal and ictal) and compared vs. each other's (matched for the phase) and controls. RESULTS: A total of 56 controls, 105 LFEM, 74 HFEM, and 32 CM were included. No differences in QST parameters were observed between LFEM, HFEM, and CM in any of the phases. During the interictal phase and when comparing with controls the following were found: 1) LFEM had lower trigeminal PPT (p = 0.001) and 2) lower cervical PPT (p = 0.001). No differences were observed between HFEM or CM and healthy controls. During the ictal phase and when comparing with controls the following were found: HFEM and CM had 1) lower trigeminal PPTs (HFEM p = 0.001; CM = p < 0.001), 2) lower cervical PPT s (HFEM p = 0.007; CM p < 0.001), and 3) higher trigeminal WUR (HFEM p = 0.001, CM p = 0.006). No differences were observed between LFEM and healthy controls. During the preictal phase and when comparing with controls the following were found: 1) LFEM had lower cervical PPT (p = 0.007), 2) HFEM had lower trigeminal (p = 0.013) and 3) HFEM had lower cervical (p = .006) PPTs. During the postictal phase and when comparing with controls the following were found: 1) LFEM had lower cervical PPT (p = 0.003), 2) HFEM had lower trigeminal PPT (p = 0.005), and 3) and HFEM had lower cervical (p = 0.007) PPTs. CONCLUSION: This study suggested that HFEM patients have a sensory profile matching CM better than LFEM. When assessing pain sensitivity in migraine populations, the phase with respects to headache attacks is of utmost importance and can explain the inconsistency in pain sensitivity data reported in the literature.

Cervical musculoskeletal impairments in the 4 phases of the migraine cycle in episodic migraine patients.

OBJECTIVE: To assess cervical musculoskeletal impairments during the 4 phases of a migraine cycle in episodic migraine patients, controlling for the presence of concomitant neck pain. METHODS: Differences in cervical musculoskeletal impairments were assessed during the 4 migraine phases in episodic migraine patients and compared with healthy controls controlling for concomitant neck pain. Cervical musculoskeletal impairments were assessed as follow: cervical active range of motion; flexion rotation test; craniocervical flexion test and calculation of activation pressure score; the total number of myofascial trigger points in head/neck muscles; the number of positivevertebral segments (headache's reproduction) during passive accessory intervertebral movement; pressure pain thresholds over C1, C2, C4, C6 vertebral segments bilaterally, trigeminal area, hand, and leg. Signs of pain sensitization were assessed by evaluating mechanical pain threshold over trigeminal area and hand, pressure pain thresholds, and the wind-up ratio. The Bonferroni-corrected p-value (05/4 = 0.013) was adopted to assess the difference between groups, while a p-value of 0.05 was considered significant for the correlation analysis. RESULTS: A total of 159 patients and 52 controls were included. Flexion rotation test and craniocervical flexion test were reduced in all 4 phases of the migraine cycle versus healthy controls (p < 0.001). The number of myofascial trigger points and positive vertebral segments was increased in all 4 phases of the migraine cycle versus healthy controls (p < 0.001). Flexion, extension, and total cervical active range of motion and cervical pressure pain thresholds were reduced in episodic migraine in the ictal phase versus controls (p < 0.007) with no other significant differences. Outside the ictal phase, the total cervical active range of motion was positively correlated with trigeminal and leg pressure pain threshold (p < 0.026), the number of active myofascial trigger points and positive positive vertebral segments were positively correlated with higher headache frequency (p=0.045), longer headache duration (p < 0.008), and with headache-related disability (p = 0.031). Cervical pressure pain thresholds were positively correlated with trigeminal, hand, and leg pressure pain threshold (p < 0.001), and trigeminal and leg mechanical pain thresholds (p < 0.005), and negatively correlated with the wind-up ratio (p < 0.004). CONCLUSION: In all phases of the migraine cycle, independent of the presence of concomitant neck pain, episodic migraine patients showed reduced flexion rotation test and craniocervical flexion test and an increased number of myofascial trigger points and passive accessory vertebral segments. These impairments are correlated with enhanced headache duration, headache-related disability, and signs of widespread pain sensitization. Reduction in active cervical movement and increased mechanical hyperalgesia of the cervical was consistent in ictal episodic migraine patients and the subgroups of episodic migraine patients with more pronounced widespread sensitization.

Trigeminal and cervical sensitization during the four phases of the migraine cycle in patients with episodic migraine.

OBJECTIVE: Assessing mechanical pain thresholds from trigeminal, cervical, and distal pain-free areas during the four phases of a migraine cycle in patients with episodic migraine (EM). METHODS: This multicenter, cross-sectional, observational study conducted in Parma and Genoa's Headache Centers assessed quantitative sensory tests during the four migraine phases in patients with EM compared to controls. Temporal summation of pain (TSP), static pressure pain threshold (sPPT), and mechanical pinprick pain threshold (MPT) were assessed from the trigeminal area, sPPT and dynamic PPT (dPPT) from the cervical area, sPPT and MPT over the hand, and sPPT from the tibialis anterior. RESULTS: A total of 135 patients and 46 controls were included. TSP was facilitated in ictal EM (EM vs. controls: mean [standard deviation] 2.7 [2.0] vs. 1.4 [1.8]; p = 0.004); trigeminal sPPT and MPT were reduced in interictal (sPPT: 198.5 [79.3] kPa; p = 0.021; MPT: 12.6 [15.7] g; p = 0.001), preictal (sPPT: 200.6 [71.6] kPa; p = 0.033; MPT: 10.7 [12.4] g; p < 0.001), ictal (sPPT: 171.4 [95.9] kPa; p < 0.001; MPT: 7.3 [12.0] g; p < 0.001), and postictal EM (sPPT: 182.2 [76.3] kPa; p = 0.006; MPT: 10.1 [14.9] g; p = 0.001), compared to controls (sPPT: 238.3 [73.8] kPa; MPT: 21.9 [17.3] g). Cervical sPPTs and dPPT were reduced in interictal (sPPT upper cervical spine: 420.5 [176.7] kPa; p = 0.031; sPPT lower cervical spine: 458.6 [207.3] kPa; p = 0.002; dPPT: 4826.5 [2698.0] g; p < 0.001), preictal (sPPT upper cervical spine: 389.3 [133.4] kPa; p = 0.006; sPPT lower cervical spine: 450.8 [174.3] kPa; p = 0.005; dPPT: 4184.2 [2628.3] g; p < 0.001), ictal (sPPT upper cervical spine: 379.9 [205.6] kPa p = 0.003; sPPT lower cervical spine: 436.3 [271.1] kPa; p = 0.001; dPPT: 3838.3 [2638.7] g; p < 0.001), and postictal EM (sPPT upper cervical spine: 385.5 [131.6] kPa; p = 0.020; sPPT lower cervical spine: 413.0 [150.3] kPa; p = 0.002; dPPT: 4679.6 [2894.9] g; p = 0.001), compared to controls (sPPT upper cervical spine: 494.9 [171.5] kPa; sPPT lower cervical spine: 586.9 [210.8] kPa; dPPT: 7693.9 [2896.8] g). Preictal EM had reduced hand sPPT and MPT (sPPT: 248.8 [96.6] kPa vs. 319.8 [112.3] kPa; p = 0.006; MPT: 23.6 [12.2] g vs. 32.5 [14.4] g; p = 0.035), while EM in the other phases showed reduction in hand MPT (interictal: 22.3 [15.6] g vs. 32.5 [14.4] g; p = 0.002; ictal: 22.4 [17.0] g vs. 32.5 [14.4] g; p = 0.004; postictal: 24.2 [18.8] g vs. 32.5 [14.4] g; p = 0.003) without significant reduction in hand sPPT. No difference in sPPT over the tibialis anterior was found. Hand MPT was negatively correlated with longer disease duration (r = -0.25; p = 0.011) and hand sPPT was negatively correlated with higher drug usage (r = -0.31; p = 0.002). TSP during the ictal phase was positively correlated with the physical (r = 0.38; p = 0.040) and emotional headache-related disability (r = 0.53; p = 0.003). CONCLUSION: In all phases of the migraine cycle, patients with EM show signs of sensitization in the trigeminocervical area, with patients with the most prominent sensitization in the ictal phase. Signs of widespread sensitization were consistent in the preictal phase in patients with EM and in the subgroups of patients with EM with the longest disease duration and more usage of symptomatic drugs.

Cervical musculoskeletal impairments and pain sensitivity in migraine patients.

INTRODUCTION: Currently, examination of migraine patients relies on a clinical interview investigating symptoms characteristics. Despite this, to help identify distinct migraine subtypes and allow a personalized treatment approach, biomarkers to profile distinct migraine subtypes should be utilized in clinical and research settings. Therefore, there is a need to include physical and psychophysical examinations aimed at assessing migraine features quantitatively. PURPOSE: This paper aimed to discuss if increased pressure pain sensitivity and impaired cervical musculoskeletal function could be considered 1) as quantitative features of migraine and 2) if they could be used as biomarkers to profile migraine patients in distinct subtypes. IMPLICATION: Increased pain sensitivity and cervical musculoskeletal impairments have been suggested as quantitative biomarkers to phenotype and subgroup migraine patients in clinical and research settings. This could provide the first step for a mechanistically-driven and personalized treatment approach according to migraine phenotypes.

Migraine patients with and without neck pain: Differences in clinical characteristics, sensitization, musculoskeletal impairments, and psychological burden.

AIMS: This study aims to assess differences in clinical characteristics across healthy controls and migraine patients with (MNP) and without (MwoNP) neck pain. METHOD: This study assessed: headache frequency; headache disability index (HDI); central sensitization inventory (CSI); Hospital Anxiety (HADS-A) and Depression (HADS-D) scale; active range of motion (AROM); flexion rotation test (FRT); activation pressure score (APS); number of active/latent myofascial trigger points (MTrPs) in head/neck muscles; number of positive cervical vertebral segments (C1/C2) who reproduce migraine pain; wind-up ratio (WUR); mechanical pain threshold (MPT) and static pressure pain threshold (sPPT) over the trigeminal area; sPPT and dynamic PPT (dPPT) over the cervical area; sPPTs and MPT over the hand. RESULTS: Compared to controls, MNP had: worse CSI, HADS-A, and HADS-D (all, p < 0.002); reduced AROM (flexion, extension, left lateral-flexion, and right-rotation), FRT, APS, and a higher number of MTrPs and positive cervical vertebral segments (all, p < 0.020); reduced trigeminal MPT and sPPT, cervical sPPT and dPPT, hand MPT and sPPT (all, p < 0.006). Compared to controls, MwoNP had: worse CSI, and HADS-A (all, p < 0.002); reduced AROM (flexion, and left lateral-flexion), FRT, APS, and a higher number of MTrPs and positive cervical vertebral segments (all, p < 0.017); reduced trigeminal MPT and cervical dPPT (all, p < 0.007). Compared to MwoNP, MNP had higher headache frequency, worse HDI and CSI (all, p < 0.006); reduced AROM (flexion, and right rotation) (all, p < 0.037); reduced cervical dPPT (all, p < 0.002). CONCLUSION: MNP had worse headache characteristics, more pronounced cervical musculoskeletal impairments, enhanced signs and symptoms related to sensitization, and worse psychological burden compared to MwoNP.

Pressure Pain Threshold of the Upper Trapezius Trigger Point: A Systematic Review with Meta-Analysis of Baseline Values and Their Modification after Physical Therapy.

BACKGROUND: Myofascial trigger points (TrP) are diagnosed upon the presence of clinical signs among which hypersensitivity is considered one of the most important. The detection of the pressure pain threshold (PPT) is used to quantify the degree of hypersensitivity. However, there is a lack of normative data about how hypersensitive a TrP is. Therefore, the objective was to quantify the PPT for myofascial TrP in the upper trapezius muscle and its modification after manual or instrumental physical therapy interventions. METHODS: A systematic review and meta-analysis were conducted among three databases (MEDLINE, Cochrane Library, and PEDro). Two independent reviewers conducted the electronic search and assessed the methodological quality of the included studies. RESULTS: Eleven studies with a high-risk bias indicated that the PPT at TrP sites was 105.11 kPa lower (95% CI: -148.93; -61.28) at active TrP sites (Chi-squared = 1.07, df = 1 (p = 0.30), I2 = 7%) compared to the PPT of the upper trapezius muscles of healthy subjects. In addition, the PPT of TrP was also lower than the reference values coming from the pain-free population. Moreover, the PPT increased after both manual and instrumental treatment by 28.36 kPa (95% CI: 10.75; 45.96) and 75.49 kPa (95% CI: 18.02; 132.95), respectively. CONCLUSIONS: The results of the present study show that TrP has a decreased PPT when compared to healthy muscles and that physical therapy may increase the PPT. However, the clinical relevance of this decreased PPT needs to be further elucidated. Further, the high risk of bias in all the retrieved studies undermines the validity of the results.

Disability, burden, and symptoms related to sensitization in migraine patients associate with headache frequency.

OBJECTIVES: This observational study aimed to assess the difference in disability, burden, and sensitization between migraine patients with low-frequency headache attack (1-8 headache days/month), high-frequency headache attack (9-14 headache days/months), and patients with chronic migraine (>14 headache days/months). METHODS: Migraine patients with or without aura were divided into three groups according to headache frequency (low-frequency episodic migraine; high-frequency episodic migraine; chronic migraine). Questionnaires were used to assess the burden of headache, quality of life, phycological burden, and symptoms related to sensitization (estimated by the Central Sensitization Inventory). Differences among migraine groups were assessed using Chi-Quadro test, ANOVA, or Kruskal-Wallis as appropriate. RESULTS: 136 patients were included (68 low-frequency episodic migraine, 45 high-frequency episodic migraine, 23 chronic migraine). Patients with high frequency episodic migraine and chronic migraine differed from patients with low frequency episodic migraine showing a worse burden of headache (p=0.002; p=0.002), worse level of physical (p=0.001; p<0.001) and mental (p=0.002; p=0.001) quality of life, worse level of depression (p=0.008; p=0.003), and increase presence of symptoms related to sensitization (p<0.001; p=0.003). No differences were found in any variables between patients with high-frequency episodic migraine and patients with chronic migraine (p>0.05). CONCLUSIONS: Patients with high-frequency episodic migraine and chronic migraine could be considered in the same segment of the migraine population, with similar degrees of disability and sensitization related symptoms.