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The exact mechanism and site of action of triptans in aborting migraine attacks remain under debate. We hypothesized that the clinical efficacy of triptans lies in aborting central sensitization and focused on the question of why triptans are headache specific, that is highly effective in migraine and cluster headache and ineffective in extracephalic pain.Forty healthy participants were enrolled in this double-blinded, randomized, placebo-controlled study. The effect of sumatriptan (n = 20) versus placebo (n = 20) was investigated in a trigeminal (V1) versus an extracephalic dermatome (forearm) using a topical capsaicin sensitization model. Capsaicin-induced primary and secondary hyperalgesia were evaluated using quantitative sensory testing.After capsaicin application, primary hyperalgesia developed in both the sumatriptan and placebo groups in both dermatomes. However, sumatriptan exclusively prevented secondary hyperalgesia in the V1 dermatome but not on the forearm. Placebo exerted no effects on secondary hyperalgesia in both trigeminal and extracephalic dermatomes. Additionally, sumatriptan reduced the flare size exclusively in the V1 dermatome.Our data suggest that sumatriptan reduces central sensitization (secondary hyperalgesia) without modulating peripheral sensitization (primary hyperalgesia) in a human pain model of capsaicin-induced sensitization. Moreover, despite a systemic administration of sumatriptan, the modulatory effects are trigeminal specific, echoing the clinical effect of triptans in aborting headaches, but not extracephalic pain.Our data suggest that triptans exert their efficacy by suppressing central sensitization. By revealing a dermatome-specific modulation, our study demonstrates a previously unrecognized interaction between the pharmacodynamics of triptans and the trigeminal nociceptive system that provides new insight into how triptans may work in aborting headache attacks.

Background The vasodilatory calcitonin-gene related peptide (CGRP) is understood as pivotal mediator in migraine pathophysiology. Blocking CGRP with small molecules or monoclonal antibodies (CGRP-mAb) reduces migraine frequency. However, prescription of CGRP-mAbs is still regulated and possible predictive measures of therapeutic success would be useful. Methods Using standardized capsaicin-induced dermal blood flow model, 29 migraine patients underwent a laser speckle imaging measurement before and after administration of galcanezumab. At both sessions dermal blood flow before and after capsaicin stimulation as well as flare size were analyzed over all three trigeminal branches and the volar forearm for extracranial control. Long-term measures were repeated in 14 patients after continuous treatment ranging from 6 to 12 months. Results Resting dermal blood flow remained unchanged after administration of galcanezumab. Capsaicin-induced dermal blood flow decreased significantly after CGRP-mAb in all tested areas compared to baseline and this was consistent even after 12 months of treatment. However, following galcanezumab administration, the flare size decreased only in the three trigeminal dermatomes, not the arm and was therefore specific for the trigemino-vascular system. None of these two markers distinguished between responders and non-responders. Conclusion CGRP-mAb changed blood flow response to capsaicin stimulation profoundly and this effect did not change over a 12-month application. Neither capsaicin-induced flare nor dermal blood flow can be used as a predictor for treatment efficacy. These data suggest that the mechanism of headache development in migraine is not entirely CGRP-mediated.

Recently it has become possible to de novo design high affinity protein binding proteins from target structural information alone. There is, however, considerable room for improvement as the overall design success rate is low. Here, we explore the augmentation of energy-based protein binder design using deep learning. We find that using AlphaFold2 or RoseTTAFold to assess the probability that a designed sequence adopts the designed monomer structure, and the probability that this structure binds the target as designed, increases design success rates nearly 10-fold. We find further that sequence design using ProteinMPNN rather than Rosetta considerably increases computational efficiency.

Galcanezumab, a monoclonal antibody against calcitonin gene-related peptide, is an emerging migraine preventative. We hypothesized that the preventive effects are conveyed via the modulation of somatosensory processing and that certain sensory profiles may hence be associated with different clinical responses. We recruited migraine patients (n = 26), who underwent quantitative sensory tests over the right V1 dermatome and forearm at baseline (T0), 2 to 3 weeks (T1) and 1 year (T12) after monthly galcanezumab treatment. The clinical response was defined as a reduction of ≥30% in headache frequency based on the headache diary. Predictors for clinical response were calculated using binary logistical regression models. After galcanezumab (T1 vs T0), the heat pain threshold (°C, 44.9 ± 3.4 vs 43.0 ± 3.3, P = 0.013) and mechanical pain threshold (log mN, 1.60 ± 0.31 vs 1.45 ± 0.26, P = 0.042) were increased exclusively in the V1 dermatome but not the forearm. These changes were immediate, did not differ between responders and nonresponders, and did not last in 1 year of follow-up (T12 vs T0). However, baseline heat pain threshold (OR: 2.13, 95% CI: 1.08-4.19, P = 0.029) on the forearm was a robust predictor for a clinical response 3 months later. In summary, our data demonstrated that galcanezumab modulates pain thresholds specifically in the V1 dermatome, but this modulation is short-lasting and irrelevant to clinical response. Instead, the clinical response may be determined by individual sensibility even before the administration of medication.

Purpose of Review The diagnostic criteria of new daily persistent headache (NDPH) have been revised since 2013. The current review focused on the progress of NDPH research over the last few years. Recent Findings Various new triggers and different NDPH mimics have been reported. The association with both cephalic and extracephalic pathologies suggests that NDPH is rather a syndrome with more than one disease mechanism. Recent clinical studies confirmed that migrainous headache remained the most prominent phenotype of NDPH, echoing the change of the diagnostic criteria in 2013. Diagnostic workup, including imaging studies, was unremarkable, except serving to exclude secondary etiologies. Studies on treatment options have yet shown promising targets, and randomized clinical trials are still lacking. Summary Multiple mechanisms, both cranial and systemic, may be involved synergically in the generation of NDPH-like headaches. The search for effective treatment options should base on better understanding of disease mechanisms.

Objective The presence of aura is rare in cluster headache, and even rarer in other trigeminal autonomic cephalalgias. We hypothesized that the presence of aura in patients with trigeminal autonomic cephalalgias is frequently an epiphenomenon and mediated by comorbid migraine with aura. Methods The study retrospectively reviewed 480 patients with trigeminal autonomic cephalalgia in a tertiary medical center for 10 years. Phenotypes and temporal correlation of aura with headache were analyzed. Trigeminal autonomic cephalalgia patients with aura were further followed up in a structured telephone interview. Results Seventeen patients with aura (3.5%) were identified from 480 patients with trigeminal autonomic cephalalgia, including nine with cluster headache, one with paroxysmal hemicrania, three with hemicrania continua, and four with probable trigeminal autonomic cephalalgia. Compared to trigeminal autonomic cephalalgia patients without aura, trigeminal autonomic cephalalgia patients with aura were more likely to have a concomitant diagnosis of migraine with aura (odds ratio [OR] = 109.0, 95% CI 30.9–383.0, p Interpretation In most patients with trigeminal autonomic cephalalgia, the presence of aura is mediated by the comorbidity of migraine with aura. Aura directly related to trigeminal autonomic cephalalgia attack may exist but remains rare. Our results suggest that aura may not be involved in the pathophysiology of trigeminal autonomic cephalalgia.

Oceanic islands are unique geographic systems that promote local adaptations and allopatric speciation in many of their highly endemic taxa. This is a common case in the Philippine Archipelago, where numerous unrelated taxa on islands have been inferred to have diversified in isolation. However, few cases have been reported in invertebrates especially among parasitic organisms. Here, we tested for biogeographical structure in novel populations of the “generalist" kleptoparasitic spider, Argyrodes lanyuensis Yoshida, Tso & Severinghaus, 1998 in the Philippines. Results showed that, in addition to Orchid/Lanyu Island, this species has a wide geographic distribution in the Philippine Archipelago. The estimated divergence time of this lineage using the mitochondrial cytochrome oxidase 1 (mt‐CO1) suggests that this species diverged ca 3.12 MYA, during the Pliocene. Two reciprocal monophyletic clades were elucidated in A. lanyuensis, but with limited differentiation across Pleistocene Aggregate Island Complex (PAIC) boundaries and modern‐day islands. However, in our analyses of morphological variation, we identified two phenotypically differentiated units in males (Orchid Island, Taiwan + Luzon, Philippine PAIC populations vs. Palawan + West Visayan + Mindanao PAIC populations). We infer that this species diverged in the southern portion of the Philippine Archipelago and only recently colonized Orchid Island. Our study provides new information on the extensive distribution of A. lanyuensis outside Orchid Island, Taiwan, but we documented a very limited geographically associated genetic variation. Our study points to behavioral phenomena such as foraging behavior as essential contributor to the evolutionary process of species diversification, in contrast to the traditionally invoked geographic drivers of divergence.

We explore the improvement of energy-based protein binder design using deep learning. We find that using AlphaFold2 or RoseTTAFold to assess the probability that a designed sequence adopts the designed monomer structure, and the probability that this structure binds the target as designed, increases design success rates nearly 10-fold. We find further that sequence design using ProteinMPNN rather than Rosetta considerably increases computational efficiency.

Research on migraine usually focuses on the headache; however, accumulating evidence suggests that migraine not only changes the somatosensory system for nociception (pain), but also the other modalities of perception, such as visual, auditory or tactile sense. More importantly, the multisensory changes exist beyond the headache (ictal) phase of migraine and show cyclic changes, suggesting a central generator driving the multiple sensory changes across different migraine phases. This review summarizes the latest studies that explored the cyclic sensory changes of migraine.Considerable evidence from recent neurophysiological and functional imaging studies suggests that alterations in brain activation start at least 48 h before the migraine headache and outlast the pain itself for 24 h. Several sensory modalities are involved with cyclic changes in sensitivity that peak during the ictal phase.In many ways, migraine represents more than just vascular-mediated headaches. Migraine alters the propagation of sensory information long before the headache attack starts.

Background:Monoclonal antibodies (mAbs) against calcitonin gene-related peptides (CGRP) are novel treatments for migraine prevention. Based on a previous functional imaging study which investigated the CGRP receptor mAb (erenumab), we hypothesized that (i) the CGRP ligand mAb galcanezumab would alter central trigeminal pain processing; (ii) responders to galcanezumab treatment would show specific hypothalamic modulation in contrast to non-responders; and (iii) the ligand and the receptor antibody differ in brain responses.Methods:Using an established trigeminal nociceptive functional magnetic imaging paradigm, 26 migraine patients were subsequently scanned twice: before and 2–3 weeks after administration of galcanezumab.Results:We found that galcanezumab decreases hypothalamic activation in all patients and that the reduction was stronger in responders than in non-responders. Contrasting erenumab and galcanezumab showed that both antibodies activate a distinct network. We also found that pre-treatment activity of the spinal trigeminal nucleus (STN) and coupling between the STN and the hypothalamus covariates with the response to galcanezumab.Conclusions:These data suggest that despite relative impermeability of the blood-brain barrier for CGRP mAb, mAb treatment induces certain and highly specific brain effects which may be part of the mechanism of their efficacy in migraine treatment.Funding:This work was supported by the German Ministry of Education and Research (BMBF) of ERA-Net Neuron under the project code BIOMIGA (01EW2002 to AM) and by the German Research Foundation (SFB936-178316478-A5 to AM). The funding sources did not influence study conduction in any way.Clinical trial number:The basic science study was preregistered in the Open Science Framework (https://osf.io/m2rc6).

Objective Headache disorders like migraine show geographic and ethnic differences between Asian and European/North American countries. In cluster headache, these differences are rarely mentioned and discussed. This article aimed to review the characteristics of cluster headache in Asian countries and compare the clinical features to those in European and North American populations. Methods We conducted a narrative literature review on the demographics, clinical presentations, and treatments of cluster headache in Asian countries. Results Patients with cluster headache in Asian populations showed a stronger male predominance compared to European and North American populations. Chronic cluster headache was rare in Asian countries. The clinical presentation of restlessness was not as common in Asian as it was in European and North American countries, and Asian patients with aura were extremely rare. Patients in Asian countries may have a lower circadian rhythmicity of cluster headache and a lower headache load, as demonstrated by lower attack frequencies per day, bout frequencies, and bout durations. Conclusions Regional differences in the presentation of cluster headache exist. Greater awareness for cluster headache should be raised in Asian regions, and further studies are warranted to elucidate the mechanisms behind observed differences.

Many animals improve their foraging success by producing signals that exploit the sensory biases of potential prey, but the specific properties that make these sensory traps effective remain unclear. We combine field experiments with phylogenetic comparative analyses to investigate the visual luring properties of different signal designs in web-building spiders. Our field experiments used cardboard spider models to examine the effects of area of colour patches, colour and pattern on the foraging success of the colourful giant wood spider, Nephila pilipes. These experiments revealed that both the colour (yellow) and pattern (yellow and black mosaic) are essential for luring prey in a high ambient light environment. We subsequently used phylogenetic comparative analyses to demonstrate an evolutionary association between prey viewing environment and spider ventral signal among 63 species of orb-weavers from 53 genera. Combined, our data show that (a) the colour of the bright body parts of orb-weavers is essential for both diurnal and nocturnal prey attraction, whereas the pattern and area of colour patches are important for diurnal foraging and (b) the evolution of these visual lures is associated with the viewing environment, specifically ambient light intensity. We conclude that the effectiveness of colour luring might be a major driver of the convergent evolution of yellow mosaic patterns in phylogenetically divergent orb-weavers. Our discoveries indicate that prey colour preferences and signal efficacy play a significant role in the evolution of visually mediated prey-luring systems. A free Plain Language Summary can be found within the Supporting Information of this article.

Migraine encompasses a broader spectrum of sensory symptoms than just headache. These “other” symptoms, eg, sensory phobias, cognitive and mood changes, allodynia, and many others indicate an altered sensitivity to sensory input which can be measured, in principle, by quantifying sensory threshold changes longitudinally over time. Photophobia, for example, can be quantified by investigating the discomfort thresholds towards the luminance of light. The aim of this review is to look into how thresholds change in patients with migraine. We performed a PubMed search up to June 2018 targeting all peer-reviewed articles evaluating the changes in threshold, sensory phobia, or sensitivity in patients with migraine. Migraineurs, in general, exhibit lower sensory thresholds compared with healthy controls. These threshold changes seem to follow the different phases during a migraine cycle. In general, thresholds reach a nadir when the headache starts (the ictal phase), rise after the headache ends, and then gradually descend towards the next attack. The sensory modality of measurement – mechanical, thermal, or nociceptive – and the location of measurement –trigeminal vs somatic dermatome – also influence the sensory threshold. Functional imaging studies provide evidence that the hypothalamo-thalamobrainstem network may be the driving force behind the periodic threshold changes. In summary, there is evidence in the literature that migraine could be understood as a periodic sensory dysregulation originating from the brain. Nevertheless, the interstudy discrepancy is still high due to different study designs and a lack of focus on distinct migraine phases. Further well-designed and harmonized studies with an emphasis on the cyclic changes still need to be conducted.

Orofacial pain (OFP) has recently been classified and subdivided into a number of groups, similar to headache disorders in the International Classification of Headache Disorders (ICHD). A novel group of OFP has been established whose major feature is that they resemble primary headache disorders occurring in the V2 or V3 dermatomes. These follow the clinical criteria and associated symptoms of the eponymous headache syndromes. Following the recent International Classification of Orofacial Pain (ICOP), three types are differentiated: Headache which spread into the face (type 1), facial pain which replaced headache but maintained the same characteristics and associated symptoms of the former headache (type 2), and de-novo orofacial pain that resembles primary headache types without any involvement of the ophthalmic trigeminal branch (type 3). The epidemiology is unclear: type 1 and 2 are not exactly common, they certainly exist in a notable proportion of headache patients, whereas type 3 may be rather rare. Since effective treatment options are available, it is important for clinicians to recognize such syndromes early to avoid misdiagnosis and unnecessary treatment, which most of these patients still experience. This review gives an up-to-date summary of diagnosis, pathophysiology and treatment of attack-like non-dental facial pain disorders.

Cluster headache and migraine are regarded as distinct primary headaches. While cluster headache and migraine differ in multiple aspects such as gender-related and headache specific features (e.g., attack duration and frequency), both show clinical similarities in trigger factors (e.g., alcohol) and treatment response (e.g., triptans). Here, we review the similarities and differences in anatomy and pathophysiology that underlie cluster headache and migraine, discuss whether cluster headache and migraine should indeed be considered as two distinct primary headaches, and propose recommendations for future studies. Graphical Abstract Video recording of the debate held at the 1st International Conference on Advances in Migraine Sciences (ICAMS 2022, Copenhagen, Denmark) is available at https://www.youtube.com/watch?v=uUimmnDVTTE.

Background Accumulating evidence suggests various specific triggers may lead to new daily persistent headache (NDPH)-like presentations, suggesting that new daily persistent headache is a heterogenous syndrome, and challenging the concept that new daily persistent headache is a primary headache disorder. Method We searched the PubMed database up to August 2022 for keywords including persistent daily headache with both primary and secondary etiologies. We summarized the literature and provided a narrative review of the clinical presentation, diagnostic work-ups, possible pathophysiology, treatment response, and clinical outcomes. Results and conclusion New daily persistent headache is a controversial but clinically important topic. New daily persistent headache is likely not a single entity but a syndrome with different etiologies. The issue with past studies of new daily persistent headache is that patients with different etiologies/subtypes were pooled together. Different studies may investigate distinct subsets of patients, which renders the inter-study comparison, both positive and negative results, difficult. The identification (and removal) of a specific trigger might provide the opportunity for clinical improvement in certain patients, even when the disease has lasted for months or years. Nonetheless, if there is a specific trigger, it remains unknown or unidentified for a great proportion of the patients. We need to continue to study this unique headache population to better understand underlying pathogenesis and, most importantly, to establish effective treatment strategies that hopefully resolve the continuous cycle of pain.

Noninvasive vagus nerve stimulation (nVNS) is effective in several types of headache disorders. We sought to unravel the mechanism of how nVNS exhibits this efficacy. This study used a randomized, single-blind, sham-controlled, crossover design and comprised 3 projects with 3 independent cohorts of healthy participants. Project I (n = 15) was explorative. Six quantitative sensory test parameters, including mechanical pain threshold (MPT), were measured over the left V1 dermatome and forearm and compared before and after unilateral nVNS. Projects II (n = 20) and III (n = 21) were preregistered online ( https://osf.io/r4jb9 ). Quantitative sensory test parameters were compared over the left (Project II) or bilateral V1 and V3 dermatomes (Project III), respectively, in addition to the left forearm as a control. A secondary analysis of heart rate variability (HRV) using a historical control group was used to control for systemic effects of nVNS. Verum-nVNS induced trigeminal-specific modulation of pain threshold (ie, MPT) over the left V1 in Project I, left V1 and V3 in Project II, and bilateral V1 and V3 in Project III. Data pooled from Projects II and III demonstrated a greater increase in MPT in the V1 vs V3 dermatome. There were no differences associated with sham-nVNS in any projects. Heart rate variability parameters did not change after nVNS. Our results provide functional evidence of a long hypothesized functional trigemino-vagal system in humans and may explain why nVNS is effective in some headache disorders but not in somatic pain disorders. Because unilateral nVNS modulated the trigeminal thresholds bilaterally, this effect is probably indirect through a central top-down mechanism.

Metal nanoclusters (NCs) with intrinsic dual-emission are not only significant for fundamental research but also for accurate ratiometric sensing and imaging. Using 1-dodecanethiol (DT) as protected-cum-reduced ligand, the core-shell structured Au-Ag bimetallic NCs with well-resolved dual-emission bands centered at 440 nm and at 630 nm were successfully synthesized by a facile one-pot approach.A combined characterizations of X-ray photoelectron spectroscopy(XPS), transmission rlectron microscope (TEM) and optical spectrum revealed that the Au-Ag bimetallic NCs had a core-shell structure with a metallic Au(0) core coated by a shell of Au(I)- and Ag(I)-thiolate motifs, and very interestingly, the dual-emissive Au-Ag NCs exhibited unique ratiometric pH-dependent emissions, which could be used an ideal pH ratiometric nanosensors. Most importantly, our observed Ag+ mediated pH-dependent dual-emissive behavior suggests that the metal NCs core is not real emitter center, while structural water molecules (SWs) confined at the nanoscale interface of metal core are true luminous centers, which answers that the optical properties of metal NCs are very sensitive to the delicate change of surrounding microenvironment of metal NCs, including the dosing of Ag+, pH and packing mode of surface ligands. Our discovery not only opens up new possibilities for the design of ultrasmall ratiometric pH nanoindicators, but also provides new insights on the origin of photoluminscent (PL) emission of metal NCs.

Background Migraine is associated with syncope. We investigated risk factors for syncope and burden of syncope in migraine patients. Methods Participants were recruited from a headache clinic. All participants provided information on lifestyle, co-morbidity, syncope, headache and suicide, and completed the MIDAS and HADS questionnaires. Genetic data were available for a subset of participants. Risk of syncope in relation to participant’s characteristics and migraine susceptibility loci, and risks of psychological disorders associated with syncope, were calculated using logistic regression. Results Underweight, regular tea intake, diabetes mellitus, and migraine with aura were associated with increased syncope risks, with adjusted ORs of 1.76 (95% CI 1.03–3.03), 1.84 (95% CI 1.22–2.79), 4.70 (95% CI 1.58–13.95), and 1.78 (95% CI 1.03–3.10), respectively. Preliminary results showed that rs11172113 in LRP1 was associated with syncope risks. Comorbid syncope in migraine patients was associated with increased risks of depression (OR 1.95, 95% CI 1.18–3.22) and suicide attempt (OR 2.85, 95% CI 1.48–5.48). Conclusion Our study showed the potential roles of vascular risk factors in the association between migraine and syncope. Modifiable risk factors for syncope in patients with migraine include body mass index and tea intake. The debilitating psychological impact of co-morbid syncope in migraine patients warrants clinical attention of treating physicians.

Understanding how animals interact with their environment is a fundamental ecological question with important implications for conservation and management. The relationships between animals and their habitat, however, can be scale-dependent. If ecologists work at suboptimal spatial scales, they will gain an incomplete picture of how animals respond to the landscape. Identifying the scale at which animal-landscape relationships are strongest (the "scale of effect") will improve our ability to better plan management and conservation activities. Several recent studies have greatly enhanced our knowledge about the scale of effect, and the potential drivers of interspecific variability, in particular life-history traits. However, while many marine systems are inherently multiscalar, research into the scale of effect has been mainly focussed on terrestrial taxa. As the scales of observation in fish-habitat association studies are often selected based on convention rather than biological reasoning, they may provide an incomplete picture of the scales where these associations are strongest. We examined fish-habitat associations across four nested spatial scales in a temperate reef system to ask: (a) at what scale are fish-habitat associations the strongest, (b) are habitat elements consistently important across scales, and (c) do scale-dependent fish-habitat associations vary in relation to either body size, geographic range size or trophic level? We found that: (a) the strongest fish-habitat associations were observed when these relationships were examined at considerably larger spatial scales than usually investigated; (b) the importance of environmental predictors varied across spatial scales, indicating that conclusions about the importance of habitat elements will depend on the scales at which studies are undertaken; and (c) scale-dependent fish-habitat associations were consistent across all life-history traits. Our results highlight the importance of considering how animals relate to their environment and suggest the small scales often chosen to examine fish-habitat associations are likely to be suboptimal. Developing a more mechanistic understanding of animal-habitat associations will greatly aid in predicting and managing responses to future anthropogenic disturbances.

Possible central effects of the monoclonal CGRP-antibody (CGRP-mAb) erenumab are not yet elucidated. This event-related, randomized, double-blind, placebo-controlled study aims to discover functional changes in pain processing after the administration of erenumab in migraine patients.

The current review provides a recapitulation of recent advances in pharmacological neuroimaging in headache, a promising tool to understanding of how a drug works in the brain and how it may lead to new insights of disease mechanisms of headache.Pharmacological positron emission tomography with radioligand-labeled medication may provide evidence whether and where a medication binds in the brain but is still mostly restricted to animal work. Pharmacological functional MRI using task-specific approaches identified central modulation patterns as a consequence of attack and preventative headache medication, which may be distinct to a specific drug mechanism. Pharmacological neuroimaging and specifically in combination with functional imaging is a promising tool to better understand not only certain medications but also certain disease mechanisms.Pharmacological imaging techniques have advanced over the last few years and showed great potential of providing new insights into drug pharmacodynamics and disease mechanism. There are still limitations and challenges to be overcome.

New daily persistent headache (NDPH) is a rare headache syndrome affecting both paediatric and adult populations. In the latest revision of International Classification of Headache Disorders, 3rd edition (ICHD-3 beta), it is defined by the onset of daily and unremitting headaches within 24 hours lasting for more than 3 months. Common triggers include flu-like symptoms and stressful life events; however, the pathophysiology is largely unknown. Regarding headache features, in the ICHD-3 beta, migrainous features are allowed in comparison with ICHD-2. Different triggers and heterogeneous clinical presentations suggest that NDPH is more likely a syndrome, rather than a disease entity. Secondary aetiologies must be carefully excluded, especially meningitis, high and low intracranial pressure headaches, medication overuse headache, or reversible cerebral vasoconstriction syndrome. There are no randomized placebo-controlled trials for NDPH; thus, the treatment is mostly empirical. Most patients have persistent headache despite treatment, but approximately one-quarter of them reached remission, usually within 24 months. However, a subgroup of those who reached remission initially might experience relapse after months or years free from pain.

Migraine is defined by attacks of headache with a specific length and associated symptoms such as photophobia, phonophobia and nausea. It is long recognized that migraine is more than just the attacks and that migraine should be understood as a cycling brain disorder with at least 4 phases: interictal, preictal, ictal and postictal. However, unlike the pain phase, the other phases are less well defined, which renders studies focusing on these phases susceptible to bias. We herewith review the available clinical, electrophysiological, and neuroimaging data and propose that the preictal phase should be defined as up to 48 hours before the headache attack and the postictal phase as up to 24 hours following the ictal phase. This would allow future studies to specifically investigate these migraine phases and to make study results more comparable.

Purpose: The current review provides a recapitulation of recent advances in pharmacological neuroimaging in headache, a promising tool to understanding of how a drug works in the brain and how it may lead to new insights of disease mechanisms of headache. Results: Pharmacological positron emission tomography with radioligand-labeled medication may provide evidence whether and where a medication binds in the brain but is still mostly restricted to animal work. Pharmacological functional MRI using task-specific approaches identified central modulation patterns as a consequence of attack and preventative headache medication, which may be distinct to a specific drug mechanism. Pharmacological neuroimaging and specifically in combination with functional imaging is a promising tool to better understand not only certain medications but also certain disease mechanisms. Summary: Pharmacological imaging techniques have advanced over the last few years and showed great potential of providing new insights into drug pharmacodynamics and disease mechanism. There are still limitations and challenges to be overcome.

Background: Non-dental orofacial pain disorders are not uncommon, but idiopathic or primary facial pain syndromes are rare. Inadequate recognition of these disorders usually leads to unsatisfactory and unmet treatment needs. Methods: We conducted a narrative review with a literature search in PubMed until December 2021, focusing on current guidelines and the recently published International Classification of Orofacial Pain (ICOP). Results: In this paper, we provide an updated overview of the common orofacial pain disorders following the ICOP, covering the classification, epidemiology, pathophysiology, clinical approaches, and treatment options. Additionally, we propose a pragmatic approach focusing on the attack duration to improve distinguishing orofacial disorders. Conclusion: The introduction of ICOP offers the opportunity to better coordinate and concentrate scientific efforts, which lays the foundation for the identification of the disease mechanism of facial pain disorders and the optimization of the currently still insufficient therapeutic strategies.

Migraine encompasses a broader spectrum of sensory symptoms than just headache. These "other" symptoms, eg, sensory phobias, cognitive and mood changes, allodynia, and many others indicate an altered sensitivity to sensory input which can be measured, in principle, by quantifying sensory threshold changes longitudinally over time. Photophobia, for example, can be quantified by investigating the discomfort thresholds towards the luminance of light. The aim of this review is to look into how thresholds change in patients with migraine. We performed a PubMed search up to June 2018 targeting all peer-reviewed articles evaluating the changes in threshold, sensory phobia, or sensitivity in patients with migraine. Migraineurs, in general, exhibit lower sensory thresholds compared with healthy controls. These threshold changes seem to follow the different phases during a migraine cycle. In general, thresholds reach a nadir when the headache starts (the ictal phase), rise after the headache ends, and then gradually descend towards the next attack. The sensory modality of measurement-mechanical, thermal, or nociceptive-and the location of measurement-trigeminal vs somatic dermatome-also influence the sensory threshold. Functional imaging studies provide evidence that the hypothalamo-thalamo-brainstem network may be the driving force behind the periodic threshold changes. In summary, there is evidence in the literature that migraine could be understood as a periodic sensory dysregulation originating from the brain. Nevertheless, the interstudy discrepancy is still high due to different study designs and a lack of focus on distinct migraine phases. Further well-designed and harmonized studies with an emphasis on the cyclic changes still need to be conducted.

The Five-hundred-meter Aperture Spherical radio Telescope is now in the commissioning stage. Due to its extreme sensitivity, it is a great challenge for FAST to mitigate the Radio Frequency Interference (RFI) not only from the telescope itself, but also from the transmitter outside the site. The solutions for RFI mitigation of FAST include the Electromagnetic Compatibility measures of the telescope and the maintenance of radio quiet zones around the site. The new pulsars detected by FAST have indicated the effectiveness of the solutions of RFI mitigation.