Pain sensitivity in men who have never experienced a headache: an observer blinded case control study.

BACKGROUND: Headache affects 90-99% of the population. Based on the question "Do you think that you never ever in your whole life have had a headache?" 4% of the population say that they have never experienced a headache. The rarity of never having had a headache suggests that distinct biological and environmental factors may be at play. We hypothesized that people who have never experienced a headache had a lower general pain sensitivity than controls. METHODS: We included 99 male participants, 47 headache free participants and 52 controls, in an observer blinded nested case-control study. We investigated cold pain threshold and heat pain threshold using a standardized quantitative sensory testing protocol, pericranial tenderness with total tenderness score and pain tolerance with the cold pressor test. Differences between the two groups were assessed with the unpaired Student's t-test or Mann-Whitney U test as appropriate. RESULTS: There was no difference in age, weight or mean arterial pressure between headache free participants and controls. We found no difference in pain detection threshold, pericranial tenderness or pain tolerance between headache free participants and controls. CONCLUSION: Our study clearly shows that freedom from headache is not caused by a lower general pain sensitivity. The results support the hypothesis that headache is caused by specific mechanisms, which are present in the primary headache disorders, rather than by a decreased general sensitivity to painful stimuli. TRIAL REGISTRATION: Registered at ClinicalTrials.gov ( NCT04217616 ), 3rd January 2020, retrospectively registered.

Increased neck muscle stiffness in migraine patients with ictal neck pain: A shear wave elastography study.

BACKGROUND: Ictal neck pain is a frequent symptom reported by half of migraine patients. It is unknown if neck pain is caused by peripheral or central mechanisms. Neck muscle stiffness can be investigated with ultrasound shear wave elastography. OBJECTIVES: To determine if migraine patients with ictal neck pain have stiffer neck muscles interictally compared with patients without ictal neck pain and controls. METHODS: This was a cross-sectional study investigating neck muscle stiffness, pressure pain thresholds and neck pain symptoms in 100 migraine patients recruited from a tertiary headache center and 46 controls. RESULTS: Patients with ictal neck pain had increased mean neck muscle stiffness interictally compared to both migraine patients without ictal neck pain (p = 0.018) and controls (p = 0.036). Muscle stiffness was negatively correlated with pressure pain thresholds in the neck in migraine patients with ictal neck pain (r = -0.292, p = 0.042). There were no differences in mean pressure pain thresholds between migraine subgroups. CONCLUSIONS: Migraine patients with ictal neck pain have stiffer neck muscles interictally compared with migraine patients without ictal neck pain and controls measured with ultrasound shear wave elastography. The increased stiffness could be due to local alterations in the neck muscles. Trial registration: clinical-trials.gov, identifier: NCT03626805.

Ictal neck pain investigated in the interictal state - a search for the origin of pain.

BACKGROUND: Neck pain is reported in more than 50% of migraine patients during migraine attacks and may be an important source to migraine pain. OBJECTIVES: To investigate phenotypical differences between migraine patients with and without ictal neck pain in the interictal phase. Additionally, to prospectively examine the association between pericranial muscle tenderness and the impending migraine attack. METHODS: Migraine patients (n = 100) and controls (n = 46) underwent a semi-structured interview and sensory testing interictally. Pericranial muscle tenderness was determined using total tenderness score and local tenderness score. The occurrence of migraine attacks was then prospectively recorded for the following seven days. RESULTS: Patients with ictal neck pain had increased tenderness of pericranial neck muscles compared to migraine patients without (p = 0.023). Ictal neck pain was not associated with migraine localization, tension-type headache, or markers of central sensitization. Prospective data of 84 patients showed that tenderness of trigeminal sensory innervated muscles increased the migraine attack rate (p = 0.035). CONCLUSION: The distinction of migraine patients based on the occurrence of ictal neck pain could indicate migraine subtypes and possible involvement of peripheral tissue in the pathophysiology. Whether treatment responses differ among these groups would be fascinating. Additionally, we found that cephalic muscle tenderness is a risk factor for an impending migraine attack.

Volume of the rectus capitis posterior minor muscle in migraine patients: a cross-sectional structural MRI study.

BACKGROUND: Neck pain in migraine patients is very prevalent between and during migraine attacks, but the underlying mechanism behind neck pain in migraine is unknown. The neck muscle rectus capitis posterior minor muscle (RCPmi) may be important since it is connected to the occipital dura mater. In this study, we examined the RCPmi volume in migraine patients and compared with controls. METHODS: We conducted a cross-sectional MRI study examining muscle volume in 40 episodic migraine patients and 40 controls in preexisting images from prior studies. Three-dimensional T1 weighted sequences were collected with a 3.0 T MRI Scanner. The volume of RCPmi was examined by manually tracing the muscle circumference with Horos medical image viewer. The observer was blinded to participant information. No information regarding neck pain status during or between migraine attacks were available. RESULTS: The mean RCPmi volume was 1.22cm3 in migraine patients and 1.17cm3 in controls (p = 0.549). We found no differences in RCPmi volume on the pain side vs. the non-pain side (p = 0.237) in patients with unilateral migraine. There were no association between the muscle volume and years with migraine, headache or migraine frequency, age or BMI. CONCLUSIONS: We found no difference in RCPmi volume between migraine patients and controls, suggesting no structural RCPmi pathology in migraine.

Myofascial trigger points in migraine and tension-type headache.

BACKGROUND: A myofascial trigger point is defined as a hyperirritable spot in skeletal muscle that is associated with a hypersensitive palpable nodule in a taut band. It has been suggested that myofascial trigger points take part in chronic pain conditions including primary headache disorders. The aim of this narrative review is to present an overview of the current imaging modalities used for the detection of myofascial trigger points and to review studies of myofascial trigger points in migraine and tension-type headache. FINDINGS: Different modalities have been used to assess myofascial trigger points including ultrasound, microdialysis, electromyography, infrared thermography, and magnetic resonance imaging. Ultrasound is the most promising of these modalities and may be used to identify MTrPs if specific methods are used, but there is no precise description of a gold standard using these techniques, and they have yet to be evaluated in headache patients. Active myofascial trigger points are prevalent in migraine patients. Manual palpation can trigger migraine attacks. All intervention studies aiming at trigger points are positive, but this needs to be further verified in placebo-controlled environments. These findings may imply a causal bottom-up association, but studies of migraine patients with comorbid fibromyalgia syndrome suggest otherwise. Whether myofascial trigger points contribute to an increased migraine burden in terms of frequency and intensity is unclear. Active myofascial trigger points are prevalent in tension-type headache coherent with the hypothesis that peripheral mechanisms are involved in the pathophysiology of this headache disorder. Active myofascial trigger points in pericranial muscles in tension-type headache patients are correlated with generalized lower pain pressure thresholds indicating they may contribute to a central sensitization. However, the number of active myofascial trigger points is higher in adults compared with adolescents regardless of no significant association with headache parameters. This suggests myofascial trigger points are accumulated over time as a consequence of TTH rather than contributing to the pathophysiology. CONCLUSIONS: Myofascial trigger points are prevalent in both migraine and tension-type headache, but the role they play in the pathophysiology of each disorder and to which degree is unclarified. In the future, ultrasound elastography may be an acceptable diagnostic test.

Pericranial Muscle Stiffness, Pain Thresholds, and Tenderness during a Treatment Cycle of OnabotulinumtoxinA for Chronic Migraine Prevention.

BACKGROUND: Treatment with OnabotulinumtoxinA (BoNT-A) is effective as a preventive treatment for chronic migraine (CM). Preclinical studies suggest that the mechanism of action of BoNT-A in migraine is based on blocking unmyelinated C fibers. We aimed to investigate whether the muscle-relaxing effect of BoNT-A is associated with the preventive mechanism in patients with chronic migraine by measuring the stiffness, pain thresholds, and tenderness of the BoNT-A-applied muscles. METHODS: A total of 22 patients with CM who were already in BoNT-A treatment participated in this longitudinal prospective study. Pericranial muscle stiffness was measured using ultrasound shear wave elastography, which measures the speed of shear waves propagating through the muscle. Pressure pain thresholds (PPT) were obtained via algometry, and muscle tenderness was measured via manual palpation. Measurements were made before BoNT-A injections and six weeks after the treatment. The measurements were performed while the muscles were maximally relaxed. The patients also completed daily diaries on headache and neck pain. RESULTS: No change was observed in muscle stiffness (p = 0.737) or pericranial muscle tenderness (p = 0.400). The PPT over the trapezius muscles increased from 250 kPa before treatment to 304 kPa six weeks after treatment (p = 0.027). No change was observed on the temporalis muscles (p = 0.200) nor the non-dominant index finger (p = 0.067). BoNT-A decreased neck pain (p = 0.008) and headache (p = 0.007). CONCLUSIONS: The findings suggest that BoNT-A leads to the desensitization of cutaneous and muscle nociceptors in the head and neck regions, whereas muscle relaxation might not be an important part of the anti-migraine effect.

Evaluating Headache and Facial Pain in a Headache Diagnostic Laboratory: Experiences from the Danish Headache Center.

BACKGROUND: Diagnostic tests are not routinely used for the diagnosis of primary headaches. It is possible that laboratory tests could be developed and implemented at tertiary headache centers to be an integrated part of the diagnosis and management of headache patients, and laboratory tests that can be used on-site at headache centers could help in evaluating patients with secondary headache disorders. METHODS: In this narrative review, we present some of the studies that have been made so far at the Headache Diagnostic Laboratory at the Danish Headache Center that aim to investigate and phenotype primary headaches and investigate secondary headaches as well as improve management. RESULTS: Semi-structured interviews and deep phenotyping, quantitative sensory testing, and provocation studies have been shown to be valuable in categorizing primary and secondary headache subtypes, possible pathophysiology, and defining needs for further research. In patients suspected of increased intracranial pressure, transorbital ultrasound with measurement of the optic sheath diameter may be useful in monitoring patients. The management of headache patients needs to be critically evaluated to optimize treatment continuously. CONCLUSION: A Headache Diagnostic Laboratory is very useful and should be an integrated part of headache care and management at tertiary headache centers.

Validation of a Digital Headache Calendar at a Tertiary Referral Center.

BACKGROUND: Headache calendars are essential tools in monitoring changes in headache frequency and type. They are used in clinical practice for long-term monitoring, but their validation remains limited. The aim of this study was to validate the use of a digital calendar in monitoring single migraine and tension-type headache attacks. METHODS: From July 2022 to February 2023, patients diagnosed with migraine and tension-type headache were enrolled. The validation of the digital calendar involved the comparison of self-reported single headache attacks in the digital calendar with the diagnostic headache diary based on the ICHD-3 criteria for migraine and tension-type headache. Sensitivity and specificity were calculated to assess reliability, and the level of agreement was calculated using kappa statistics. RESULTS: This study included 30 patients (87% women) diagnosed with migraine and tension-type headache. The level of agreement in the classification of a single migraine attack revealed a sensitivity of 82% and a specificity of 78%, representing a substantial level of agreement (κ = 0.60). The classification of a single tension-type headache attack revealed a sensitivity of 84% and a specificity of 72%, with a moderate level of agreement (κ = 0.54). CONCLUSIONS: The digital calendar proves effective in monitoring single headache attacks in patients with migraine and tension-type headache. In clinical practice, we recommend using the digital calendar as a monitoring tool for headache patients, as they can accurately identify true migraine and tension-type headache days.

Intracranial Pressure: A Comparison of the Noninvasive HeadSense Monitor versus Lumbar Pressure Measurement.

OBJECTIVE: To compare a new method of noninvasive intracranial pressure (nICP) measurement with conventional lumbar puncture (LP) opening pressure. METHODS: In a prospective multicenter study, patients undergoing LP for diagnostic purposes underwent intracranial pressure measurements with HeadSense, a noninvasive transcranial acoustic device, and indirectly with LP. Noninvasive measurements were conducted with the head in a 30° tilt and in supine position before and after LP. The primary endpoint was the correlation between nICP measurement in supine position before LP and the LP opening pressure. RESULTS: There was no correlation between supine nICPs before LP and the LP opening pressures (r = -0.211, P = 0.358). The 30° head-tilt nICPs correlated with the supine nICPs before LP (r = 0.830, P < 0.01). There was no correlation between supine nICPs before and after LP (r = 0.056, P = 0.831) or between 30° head-tilt nICPs and LP opening pressures (r = -0.038, P = 0.861). CONCLUSIONS: There was no correlation between nICPs and LP opening pressures. Further development is warranted before transcranial acoustic HeadSense can become a clinical tool for investigating patients with neurologic conditions.

Validity and reliability of grade scoring in the diagnosis of exercise-induced laryngeal obstruction.

The current gold-standard method for diagnosing exercise-induced laryngeal obstruction (EILO) is continuous laryngoscopy during exercise (CLE), with severity classified by a visual grade scoring system. We evaluated the precision of this approach, by evaluating test-retest reliability of CLE and both inter- and intra-rater variability. In this prospective case-control study, subjects completed four consecutive treadmill CLE tests under identical conditions. Laryngoscopic video recordings were anonymised and graded by three expert raters. 2 months following initial scoring, videos were re-randomised and rating repeated to assess intra-rater agreement. 20 subjects (16 cases and four controls) completed four CLE tests. The time to exhaustion increased by 30 s (95% CI 0.02-57.8, p<0.05) in the second CLE compared with the first test, but remained identical in the subsequent tests. Only one-third of subjects retained their initial diagnosis in the subsequent three tests. Inter-rater agreement on grade scores (weighted Cohen's ϰ) was 0.16-0.45, while intra-rater agreement ranged from 0.30 to 0.67. The CLE test is key in the diagnostic assessment of patients with EILO. However, the widely adopted visual grade scoring system does not appear to be a robust means for reliably classifying severity of EILO.