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.

Headache onset after vaccination against SARS-CoV-2: a systematic literature review and meta-analysis.

BACKGROUND: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are used to reduce the risk of developing Coronavirus Disease 2019 (COVID-19). Despite the significant benefits in terms of reduced risk of hospitalization and death, different adverse events may present after vaccination: among them, headache is one of the most common, but nowadays there is no summary presentation of its incidence and no description of its main features. METHODS: We searched PubMed and EMBASE covering the period between January 1st 2020 and August 6th, 2021, looking for record in English and with an abstract and using three main search terms (with specific variations): COVID-19/SARS-CoV-2; Vaccination; headache/adverse events. We selected manuscript including information on subjects developing headache after injection, and such information had to be derived from a structured form (i.e. no free reporting). Pooled estimates and 95% confidence intervals were calculated. Analyses were carried out by vaccine vs. placebo, by first vs. second dose, and by mRNA-based vs. "traditional" vaccines; finally, we addressed the impact of age and gender on post-vaccine headache onset. RESULTS: Out of 9338 records, 84 papers were included in the review, accounting for 1.57 million participants, 94% of whom received BNT162b2 or ChAdOx1. Headache was generally the third most common AE: it was detected in 22% (95% CI 18-27%) of subjects after the first dose of vaccine and in 29% (95% CI 23-35%) after the second, with an extreme heterogeneity. Those receiving placebo reported headache in 10-12% of cases. No differences were detected across different vaccines or by mRNA-based vs. "traditional" ones. None of the studies reported information on headache features. A lower prevalence of headache after the first injection of BNT162b2 among older participants was shown. CONCLUSIONS: Our results show that vaccines are associated to a two-fold risk of developing headache within 7 days from injection, and the lack of difference between vaccine types enable to hypothesize that headache is secondary to systemic immunological reaction than to a vaccine-type specific reaction. Some descriptions report onset within the first 24 h and that in around one-third of the cases, headache has migraine-like features with pulsating quality, phono and photophobia; in 40-60% of the cases aggravation with activity is observed. The majority of patients used some medication to treat headache, the one perceived as the most effective being acetylsalicylic acid.

Variables associated with use of symptomatic medication during a headache attack in individuals with tension-type headache: a European study.

BACKGROUND: Pharmacological treatment of patients with tension-type headache (TTH) includes symptomatic (acute) and prophylactic (preventive) medication. No previous study has investigated variables associated to symptomatic medication intake in TTH. Our aim was to assess the association of clinical, psychological and neurophysiological outcomes with the use and timing of the use of symptomatic medication in TTH. METHODS: A longitudinal observational study was conducted. One hundred and sixty-eight (n = 168) patients with TTH participated. Pain features of the headache (intensity, frequency, duration), burden of headache (Headache Disability Inventory), sleep quality (Pittsburgh Sleep Quality Index), anxiety/depression (Hospital Anxiety and Depression Scale), trait/state anxiety levels (State-Trait Anxiety Inventory), and bilateral pressure pain thresholds on the temporalis, C5-C6 joint, second metacarpal and tibialis anterior were assessed. Symptomatic medication intake was also collected for a 6-months follow-up period. Differences between patients using or not using symptomatic medication, depending on self-perceived effectiveness, and time (early during an attack, i.e., the first 5 min, or when headache attack is intense) when the symptomatic medication was taken were calculated. RESULTS: One hundred and thirty-six (n = 136, 80%) reported symptomatic medication intake for headache (73% NSAIDs). Sixteen (12%) reported no pain relief, 81 (59%) experienced moderate relief and 39 (29%) total pain relief. Fifty-eight (43%) took 'early medication' whereas 78 (57%) took 'late medication'. Patients taking symptomatic medication in general showed lower headache frequency and lower depressive levels than those patients not taking medication. Symptomatic medication was more effective in patients with lower headache history, frequency, and duration, and lower emotional burden. No differences in pressure pain sensitivity were found depending on the self-perceived effectiveness of medication. Patients taking 'late symptomatic' medication exhibited more widespread pressure pain sensitivity than those taking 'early medication'. CONCLUSIONS: This study found that the effectiveness of symptomatic medication was associated with better headache parameters (history, frequency, or duration) and lower emotional burden. Further, consuming early symptomatic medication at the beginning of a headache attack (the first 5 min) could limit widespread pressure pain sensitivity.

Gender differences in clinical and psychological variables associated with the burden of headache in tension-type headache.

Our aim was to assess gender differences in variables associated with the emotional and physical burdens of tension-type headache (TTH). Participants with TTH diagnosed according to the ICHD-III were recruited from three university-based hospitals (in Spain, Italy, Denmark) between January 2015 and June 2017. The physical/emotional headache burden was assessed with the Headache Disability Inventory (HDI-P/HDI-E, respectively). Headache features were collected with a four-week diary. Sleep quality was assessed with Pittsburgh Sleep Quality Index. The Hospital Anxiety and Depression Scale evaluated anxiety and depressive symptom levels. Trait and state anxiety levels were evaluated with the State-Trait Anxiety Inventory. Two hundred and twelve (28% men) participants (aged 41-48 years old) participated. Multiple regression models revealed that sleep quality explained 36.7% of the variance of HDI-E and 31.1% of the variance of HDI-P in men, whereas headache intensity, depressive levels, and younger age explained 37.5% of the variance of HDI-E and 32.8% of the variance of HDI-P in women (all p < .001). This study observed gender differences in variables associated with headache burden in TTH. Management of men with TTH should focus on interventions targeting sleep quality, whereas the management of women with TTH should combine psychological approaches and interventions targeting pain mechanisms.

Widespread Pressure Pain Hypersensitivity, Health History, and Trigger Points in Patients with Chronic Neck Pain: A Preliminary Study.

BACKGROUND: Pain sensitivity in chronic neck pain patients may be influenced by health conditions related to higher levels of widespread pressure pain hypersensitivity (sensitization). Trigger points have also been reported to play a role in the sensitization process. OBJECTIVES: To investigate the association between pressure pain thresholds, trigger points, and health conditions in patients with chronic neck pain. DESIGN: Original research, preliminary study. SETTING: A private clinic. SUBJECTS: Thirty-four chronic mechanical neck pain patients and 34 chronic whiplash-associated neck pain patients, giving a final sample of 68 chronic neck pain patients. METHODS: Patients underwent an assessment of pressure pain thresholds over the upper trapezius, extensor carpi radialis longus, and tibialis anterior muscles and were screened for the presence of trigger points in the upper trapezius muscle. Further, information about health history conditions was obtained and collected in a form. RESULTS: Significantly negative correlations between all pressure pain thresholds and duration of health history conditions were found (all P < 0.02). Significantly lower pressure pain thresholds (all P < 0.01) were found in patients with active trigger points as compared with those with latent trigger points. CONCLUSION: Widespread pressure pain hypersensitivity was associated with duration of health history conditions, suggesting that long-lasting health complaints may act as a triggering/perpetuating factor, driving sensitization in individuals with chronic neck pain. Active trigger points may be associated with higher widespread pressure hypersensitivity.

Trigger points are associated with widespread pressure pain sensitivity in people with tension-type headache.

Objective To investigate the association between trigger points (TrPs) and widespread pressure pain sensitivity in people with tension-type headache (TTH) and to determine if this association is different between frequent episodic (FETTH) or chronic (CTTH) headache. Design A cross-sectional study. Methods One hundred and fifty-seven individuals (29% male) with TTH participated. Clinical features of headache, i.e., intensity, duration, and frequency, were recorded in a headache diary. Active and latent TrPs were bilaterally explored in the temporalis, masseter, suboccipital, upper trapezius, sternocleidomastoid, and splenius capitis muscles. Pressure pain thresholds (PPT) were assessed over the trigeminal area (i.e., temporalis muscle), extra-trigeminal (i.e., C5/C6 zygapophyseal joint), and two distant pain-free points (i.e., second metacarpal and tibialis anterior muscle). Results Eighty (51%) patients were classified as FETTH, whereas 77 (49%) were classified as CTTH. No differences in the number of either active or latent TrPs (all p > 0.171) or widespread pressure pain sensitivity (all p > 0.351) were observed between FETTH and CTTH groups. The number of active and latent TrPs was significantly and negatively associated with PPTs: The higher the number of active or latent TrPs, the lower the widespread PPT, and the more generalized sensitization. This association was stronger within the FETTH group than the CTTH group. Conclusions This study found that the number of TrPs in head and neck/shoulder muscles was associated with widespread pressure hypersensitivity independently of the frequency of headache.

Widespread Pressure Pain Hypersensitivity Is Similar in Women With Frequent Episodic and Chronic Tension-Type Headache: A Blinded Case-Control Study.

OBJECTIVE: To investigate differences in widespread pressure pain hyperalgesia in the trigemino-cervical and extra-trigeminal (distant pain-free) regions in women with frequent episodic (FETTH) and chronic (CTTH) tension-type headache. BACKGROUND: It seems that people with tension-type headache exhibit central sensitization. No study has investigated differences between FETTH and CTTH in terms of widespread pressure pain hypersensitivity. METHODS: Forty-three women with FETTH, 42 with CTTH, and 45 women without headache diagnosis were recruited. Pressure pain thresholds (PPTs) were bilaterally assessed over trigeminal area (ie, temporalis muscle), extra-trigeminal (ie, C5/C6 zygapophyseal joint), and two distant points (ie, second metacarpal and tibialis anterior muscle) by a blinded assessor. Clinical features of the headache were collected with a 4-week headache diary. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). RESULTS: The ANCOVA revealed that PPTs were significantly decreased bilaterally over trigeminal (mean differences ranging from 97.5 to 101.5 kPa), extra-trigeminal (from 94.3 to 114.5 kPa), and distant points (from 99.4 to 208.6 kPa) in both FETTH and CTTH groups compared with controls (all, P < .001). No differences between FETTH and CTTH were observed (all points, P > .217). Anxiety (all, P > .803) or depression (P > .206) did not influence pressure pain hyperalgesia. No associations between widespread pressure hypersensitivity and headache features were observed (all, P > .110). CONCLUSIONS: Current results suggest the presence of similar local and widespread pressure hyperalgesia, not associated with anxiety or depression, in women with FETTH and CTTH supporting that localized and central manifestations are involved in both the episodic and chronic forms of tension-type headache.

Do Subjects with Whiplash-Associated Disorders Respond Differently in the Short-Term to Manual Therapy and Exercise than Those with Mechanical Neck Pain?

Objective: To compare the short-term effects of manual therapy and exercise on pain, related disability, range of motion, and pressure pain thresholds between subjects with mechanical neck pain and whiplash-associated disorders. Methods: Twenty-two subjects with mechanical neck pain and 28 with whiplash-associated disorders participated. Clinical and physical outcomes including neck pain intensity, neck-related disability, and pain area, as well as cervical range of motion and pressure pain thresholds over the upper trapezius and tibialis anterior muscles, were obtained at baseline and after the intervention by a blinded assessor. Each subject received six sessions of manual therapy and specific neck exercises. Mixed-model repeated measures analyses of covariance (ANCOVAs) were used for the analyses. Results: Subjects with whiplash-associated disorders exhibited higher neck-related disability ( P = 0.021), larger pain area ( P = 0.003), and lower pressure pain thresholds in the tibialis anterior muscle ( P = 0.009) than those with mechanical neck pain. The adjusted ANCOVA revealed no between-group differences for any outcome (all P > 0.15). A significant main effect of time was demonstrated for clinical outcomes and cervical range of motion with both groups experiencing similar improvements (all P < 0.01). No changes in pressure pain thresholds were observed in either group after treatment ( P > 0.222). Conclusions: The current clinical trial found that subjects with mechanical neck pain and whiplash-associated disorders exhibited similar clinical and neurophysiological responses after a multimodal physical therapy intervention, suggesting that although greater signs of central sensitization are present in subjects with whiplash-associated disorders, this does not alter the response in the short term to manual therapy and exercises.

Identification of subgroups of patients with tension type headache with higher widespread pressure pain hyperalgesia.

BACKGROUND: Identification of subgroups of patients with different levels of sensitization and clinical features can help to identify groups at risk and the development of better therapeutic strategies. The aim of this study was to identify subgroups of patients with tension type headache (TTH) with different levels of sensitization, clinical pain features, and psychological outcomes. METHODS: A total of 197 individuals with TTH participated. Headache intensity, frequency, and duration and medication intake were collected with a 4-weeks diary. Pressure pain thresholds were assessed bilaterally over the temporalis muscle, C5-C6 joint, second metacarpal and tibialis anterior muscle to determine widespread pressure pain hyperalgesia. The Hospital Anxiety and Depression Scale assessed anxiety and depression. The State-Trait Anxiety Inventory evaluated the state and trait levels of anxiety. The Headache Disability Inventory evaluated the burden of headache. Health-related quality of life was determined with the SF-36 questionnaire. Groups were considered as positive (three or more criteria) or negative (less than three criteria) on a clinical prediction rule: headache duration <8.5 h/day; headache frequency <5.5 days/week; bodily pain <47 and vitality <47.5. RESULTS: The ANCOVA revealed that subjects in group 1 (positive rule, n = 89) exhibited longer headache history, shorter headache duration, lower headache frequency, higher widespread pressure hyperalgesia, higher anxiety trait levels, and lower quality of life (all, P < 0.01) than those subjects within group 2 (negative rule, n = 108). Differences were similar between men and women. CONCLUSIONS: This study identified a subgroup of patients with TTH with higher sensitization, higher chronicity of headaches and worse quality of life but lower frequency and duration of headache episodes. This subgroup of individuals with TTH may need particular attention and specific therapeutic programs for avoiding potential chronification.

The association of headache frequency with pain interference and the burden of disease is mediated by depression and sleep quality, but not anxiety, in chronic tension type headache.

BACKGROUND: A better understanding of potential relationship between mood disorders, sleep quality, pain, and headache frequency may assist clinicians in determining optimal therapeutic programs. The aim of the current study was to analyze the effects of sleep quality, anxiety, depression on potential relationships between headache intensity, burden of headache, and headache frequency in chronic tension type headache (CTTH). METHODS: One hundred and ninety-three individuals with CTTH participated. Headache features were collected with a 4-weeks headache diary. The Hospital Anxiety and Depression Scale was used for assessing anxiety and depression. Headache Disability Inventory evaluated the burden of headache. Pain interference was determined with the bodily pain domain (SF-36 questionnaire). Sleep quality was assessed with Pittsburgh Sleep Quality Index. Path analyses with maximum likelihood estimations were conducted to determine the direct and indirect effects of depression, anxiety, and sleep quality on the frequency of headaches. RESULT: Two paths were observed: the first with depression and the second with sleep quality as mediators. Direct effects were noted from sleep quality, emotional burden of disease and pain interference on depression, and from depression to headache frequency. The first path showed indirect effects of depression from emotional burden and from sleep quality to headache frequency (first model R 2 = 0.12). Direct effects from the second path were from depression and pain interference on sleep quality and from sleep quality on headache frequency. Sleep quality indirectly mediated the effects of depression, emotional burden and pain interference on headache frequency (second model R 2 = 0.18). CONCLUSIONS: Depression and sleep quality, but not anxiety, mediated the relationship between headache frequency and the emotional burden of disease and pain interference in CTTH.

The burden of headache is associated to pain interference, depression and headache duration in chronic tension type headache: a 1-year longitudinal study.

BACKGROUND: To investigate variables associated at one year (longitudinal design) with the physical or emotional component of burden in chronic tension type headache (CTTH). METHODS: One hundred and thirty (n = 130) individuals with CTTH participated in this longitudinal study. Clinical features were collected with a 4-weeks headache diary at baseline and 1-year follow-up. The burden of headache was assessed at baseline and one -year follow-up with the Headache Disability Inventory (HDI), physical (HDI-P) or emotional (HDI-E) component. Sleep quality (Pittsburgh Sleep Quality Index), anxiety and depression (Hospital Anxiety and Depression Scale-HADS), and quality of life (SF-36) were also assessed at baseline. Hierarchical regression analyses were conducted to determine the associations between the baseline variables and the headache burden at 1-year. Simple mediation models were also applied to determine the potential mediation effect of any intermediary variable. RESULTS: Regression analyses revealed that baseline pain interference and depression explained 32% of the variance in the emotional burden of headache, whereas baseline emotional burden of the headache, pain interference, and headache duration explained 51% of the variance in the physical burden of headache (P < .01) at 1-year. The mediation models observed that the effect of baseline pain interference on emotional burden of headache at 1-year was mediated through baseline depression, whereas the effect of baseline pain interference on the physical burden of headache at 1-year was mediated through baseline emotional burden of headache (both P < .05). CONCLUSIONS: The current study found a longitudinal interaction between pain interference and depression with the burden of headache in individuals with CTTH.

Topographical Pressure Pain Sensitivity Maps of the Temporalis Muscle in People with Frequent Episodic and Chronic Tension-Type Headache.

BACKGROUND: Previous pilot studies suggest the presence of heterogeneous sensitivity to pressure in primary headaches without considering the frequency of headache episodes. OBJECTIVE: To investigate the differences in topographical pressure pain sensitivity maps in the temporalis muscle between individuals with frequent episodic (FETTH) and chronic (CTTH) tension-type headache by controlling the presence of anxiety and depression. METHODS: oPressure pain thresholds (PPTs) were assessed bilaterally from 9 points distributed over the temporalis muscle (3 points in the anterior portion, 3 in the middle portion, and the remaining 3 in the posterior portion of the muscle belly) in 113 patients with FETTH and 91 with CTTH in a blinded design. Topographical pressure pain sensitivity maps based on interpolation of the PPTs were constructed. Clinical features of headache were collected in a 4-week headache diary. Anxiety and depression (Hospital Anxiety and Depression Scale) were also assessed. RESULTS: The multilevel analysis of covariance found significant difference in PPT levels between points (F = 47.649; P < 0.001), but not between groups (F = 0.801; P = 0.602) or sides (F = 0.331; P = 0.565). No significant effect of gender (F = 0.785; P = 0.667), depression (F = 0.515; P = 0.846), or anxiety (F = 0.639; P = 0.745) was observed. Post hoc comparisons revealed: (1) no differences between FETTH and CTTH; (2) no side-to-side differences; and (3) anterior-to-posterior gradient with the most sensitive points located in the anterior column, followed by those located in the central column and the posterior column of the muscle (all, P < 0.001). CONCLUSIONS: This study confirmed an anterior-to-posterior gradient of sensitivity to pressure in both groups, with the highest sensitivity at the anterior part of the muscle. Further, we found similar pressure pain sensitivity in the trigeminal area in people with FETTH or CTTH with no association with depressive or anxiety levels.

Myofascial trigger points in patients with whiplash-associated disorders and mechanical neck pain.

OBJECTIVE: The aim of this study was to investigate pain patterns and the distribution of myofascial trigger points (MTPs) in whiplash-associated disorders (WADs II and III) as compared with mechanical neck pain (MNP). METHODS: Manual examination of suboccipital, upper trapezius, elevator scapula, temporalis, supraspinatus, infraspinatus, deltoid, and sternocleidomastoid muscles, was done to search for the presence of both active or latent MTPs in 49 WAD patients and 56 MNP patients. Local pain and referred pain from each active MTP was recorded on an anatomical map. RESULTS: The mean number of active MTPs was significantly greater in the WAD group (6.71 ± 0.79) than in the MNP group (3.26 ± 0.33) (P < 0.001), but this was not found for the latent MTPs (3.95 ± 0.57 vs. 2.82 ± 0.34; P > 0.05). In the WAD group, the current pain intensity (visual analogue scale) of the patients was significantly correlated with the number of active MTPs (rs = 0.03, P = 0.03) and the spontaneous pain area (rs = 0.25, P = 0.07), and the number of active MTPs was significantly correlated with the spontaneous pain area (rs = 0.3, P = 0.03). In the MNP group, significant correlation was found only between pain duration and spontaneous pain area (rs = 0.29, P = 0.02). CONCLUSIONS: Active MTPs are more prominent in WAD than MNP and related to current pain intensity and size of the spontaneous pain distribution in whiplash patients. This may underlie a lower degree of sensitization in MNP than in WAD.

Prevalence and Risk Factors of Multitype Post-COVID Pain in a Cohort of Previously Hospitalized COVID-19 Survivors: A Danish Cross-Sectional Survey.

This population-based study investigated the prevalence of de novo, multitype, post-coronavirus disease (COVID) pain and its associated risk factors in previously hospitalized coronavirus disease 2019 (COVID-19) survivors. The nationwide, cross-sectional study included a cohort of Danish residents previously hospitalized due to severe acute respiratory syndrome coronavirus-2 infection between March 2020 and December 2021. Demographic data, preexisting medical comorbidities, previous pain-related symptoms, medication use for pain management, pain intensity (4-point scale), and development of de novo, multitype, post-COVID pain were collected by a self-reported survey distributed via e-Boks (a secured national digital mail system used in Denmark to provide public information to residents). The sample comprised 4,712 previously hospitalized COVID-19 survivors (48.6% women, mean age: 60.1 ± 15.6 years). At the time of the study (21 ± 6 months after hospitalization), 18.0% (847) reported the presence of de novo, multitype, post-COVID pain, and 38.6% of any pain. A multivariate analysis revealed that female sex (Odds Ratio (OR) 1.711, 95% Confidence Interval (CI) 1.444-2.023), higher body mass index (OR 1.032, 95% CI 1.019-1.045), intensive care unit admission (OR 1.597, 95% CI 1.324-1.926), previous history of whiplash (OR 2.471, 95% CI 1.004-6.081), anxiety (OR 3.626, 95% CI 1.335-9.708), and younger age (OR .982, 95% CI .976-.987) were factors associated with development of de novo, multitype, post-COVID pain. High income (OR .635, 95% CI .494-.817) and high educational level (OR .774, 95% CI .609-.984) were protective factors. In conclusion, multitype pain as a de novo post-COVID symptom was present in 18.0% of previously hospitalized COVID-19 survivors more than 1 year after hospital discharge and as such can be considered as adding to the global burden of chronic pain. PERSPECTIVE: The study investigates the prevalence of de novo, multitype, post-COVID pain in previously hospitalized COVID-19 survivors. This article presents potential risk factors associated with developing new pain symptoms. The results will contribute to understanding the possibility of predicting postinfectious pain from COVID-19 for future analysis.