Exploring Novel Therapeutic Targets in the Common Pathogenic Factors in Migraine and Neuropathic Pain.

Migraine and neuropathic pain (NP) are both painful, disabling, chronic conditions which exhibit some symptom similarities and are thus considered to share a common etiology. The calcitonin gene-related peptide (CGRP) has gained credit as a target for migraine management; nevertheless, the efficacy and the applicability of CGRP modifiers warrant the search for more effective therapeutic targets for pain management. This scoping review focuses on human studies of common pathogenic factors in migraine and NP, with reference to available preclinical evidence to explore potential novel therapeutic targets. CGRP inhibitors and monoclonal antibodies alleviate inflammation in the meninges; targeting transient receptor potential (TRP) ion channels may help prevent the release of nociceptive substances, and modifying the endocannabinoid system may open a path toward discovery of novel analgesics. There may exist a potential target in the tryptophan-kynurenine (KYN) metabolic system, which is closely linked to glutamate-induced hyperexcitability; alleviating neuroinflammation may complement a pain-relieving armamentarium, and modifying microglial excitation, which is observed in both conditions, may be a possible approach. Those are several potential analgesic targets which deserve to be explored in search of novel analgesics; however, much evidence remains missing. This review highlights the need for more studies on CGRP modifiers for subtypes, the discovery of TRP and endocannabinoid modulators, knowledge of the status of KYN metabolites, the consensus on cytokines and sampling, and biomarkers for microglial function, in search of innovative pain management methods for migraine and NP.

Cluster headache and kynurenines.

BACKGROUND: The glutamatergic neurotransmission has important role in the pathomechanism of primary headache disorders. The kynurenine metabolites derived from catabolism of tryptophan (Trp) have significant involvement not only in glutamatergic processes, but also in the neuroinflammation, the oxidative stress and the mitochondrial dysfunctions. Previously we identified a depressed peripheral Trp metabolism in interictal period of episodic migraineurs, which prompted us to examine this pathway in patients with episodic cluster headache (CH) as well. Our aims were to compare the concentrations of compounds both in headache-free and attack periods, and to find correlations between Trp metabolism and the clinical features of CH. Levels of 11 molecules were determined in peripheral blood plasma of healthy controls (n = 22) and interbout/ictal periods of CH patients (n = 24) by neurochemical measurements. FINDINGS: Significantly decreased L-kynurenine (KYN, p < 0.01), while increased quinolinic acid (QUINA, p < 0.005) plasma concentrations were detected in the interbout period of CH patients compared to healthy subjects. The levels of KYN are further reduced during the ictal period compared to the controls (p < 0.006). There was a moderate, negative correlation between disease duration and interbout QUINA levels (p < 0.048, R = - 0.459); and between the total number of CH attacks experienced during the lifetime of patients and the interbout KYN concentrations (p < 0.024, R = - 0.516). Linear regression models revealed negative associations between age and levels of Trp, kynurenic acid, 3-hdyroxyanthranilic acid and QUINA in healthy control subjects, as well as between age and ictal level of anthranilic acid. CONCLUSIONS: Our results refer to a specifically altered Trp metabolism in CH patients. The onset of metabolic imbalance can be attributed to the interbout period, where the decreased KYN level is unable to perform its protective functions, while the concentration of QUINA, as a toxic compound, increases. These processes can trigger CH attacks, which may be associated with glutamate excess induced neurotoxicity, neuroinflammation and oxidative stress. Further studies are needed to elucidate the exact functions of these molecular alterations that can contribute to identify new, potential biomarkers in the therapy of CH.

[Sumatriptan-naproxen sodium fix-dose combination for acute migraine treatment, a review]. / Szumatriptán­naproxén-nátrium fix dózisú kombinációja a migrén akut kezelésében ­ irodalmi áttekintés.

Migraine as a common primary headache disorder has a significant negative effect on quality of life of the patients. Its pharmacotreatment includes acute and preventative therapies. Based on the shared therapeutic guideline of the European Headache Federation and the European Academy of Neurology for acute migraine treatment a combination of triptans and non-steroidal anti-inflammatory drugs is recommended for acute migraine treatment in triptan-nonresponders. In this short review we summarized the results of the randomized controlled clinical trials evaluating the effectiveness and safety of sumatriptan (85 mg)/naproxen sodium (500 mg) fix-dose combination. It was revealed that the fix-dose combination was better than placebo for the primary outcomes of exemption of pain and headache relief at 2 hours. Furthermore the combination showed beneficial effect on accompanying symptoms of migraine attack (i.e. nausea, photo- and phonophobia). Adverse events were mild or moderate in severity and rarely led to withdrawal of the drug.
It can be concluded that sumatriptan (85 mg)/naproxen sodium (500 mg) fix-dose combination is effective, safe and well-tolerated in the acute treatment of migraine. 

[Headache registry in Szeged: Experiences regarding to migraine patients]. / Fejfájásregiszter kialakításával szerzett szegedi tapasztalataink migrénes betegek vonatkozásában.

Background and purpose:

Using patient registries is essential both in clinical research and in medical practice. Headaches, more specifically migraines are one of the most common complaints that can detract the quality of a patient’s life and these complaints also have a significant socio-econo­mic effect. Our goal is to create a national Headache Registry and to also provide the pre-analysis of the registry’s database.

Our research is based on the national Multiple Sclerosis Registry, which we modified using the latest version of diagnostic criteria published by the International Headache Society. This clinical study contains data collected from patients suffering from migraines and currently receiving care at the Headache Outpatient Department at the Neurologic Clinic of the University of Szeged.

The data of 412 patients (363 wo­men and 49 men) suffering from migraine (migraine without aura: n = 313 and migraine with aura: n = 99) were added to the Headache Registry. The average age of participants was 44.1 ± 12.5 SD years. Regarding the attributes of migraine headaches we examined the following characteristics: localization, quality and intensity (based on the Visual Analogue Scale) of the pain, frequency (the number of headache days per month), medications (acute or prophylactic), comorbidities (depression, anxiety, hypertension, asthma, epilepsy and others), family history and the occurrence of stroke among patients.

Based on international expe­rience, patient registries are the most optimal systems for structured patient mo­nitoring. For high level management and long-term follow up of the patients the application of registries is essential. The registries include the detailed medical history and the diagnostic and therapeutic data of the patients, and they trace the changes during the follow up medical visits. Registries are able to record the entire course of the disease in digital way. The numerous data can be set out any time from the digital database. Extensive spread of patients’ registries is fundamental not only in every day clinical practice, but also in clinical research.

[Neurosyphilis or not - a case of a differential diagnostic challenge]. / Neurosyphilis vagy nem ­ egy differenciáldiagnosztikai kihívás esete.

We report the case of a 42-year-old woman with paraparesis associated with transverse myelitis. For differential diagnostics detailed microbiological, cerebrospinal fluid (CSF) and neuroimaging examinations were performed. Syphilis was confirmed, but diagnosis of neurosyphilis was only probable based on the CSF microbiological test results. The beneficial treatment response to application of the therapeutic protocol for syphilis supported the supposed diagnosis of syphilis-associated myelitis in our case. In this case report we reviewed the differential diagnostic tools of myelopathies/myelitis.
Nowadays regarding to growing prevalence of syphilis worldwide physicians should face on its presence and medical consequences.

[COVID-19 and chronic pain: online survey in the domestic population]. / Covid-19 és krónikus fájdalom: online felmérés a pandémia alatt fájdalommal élo, ellátásban nem részesülo személyek körében.

Background and purpose: The problems caused by the COVID-19 epidemic have the worst impact on chronic patient populations. People with chronic pain are one of the most vulnerable groups due to stress, disruption of daily routine, family problems, illness and difficulty in hospital care. It is therefore essential to assess the situation and mental well-being of this group. The aim of this survey was to assess chronic pain patients during the COVID-19 pandemic, addressing psychological background factors that might affect pain symptoms, such as depression, emotion regulation, alexithymia, well-being, health literacy and social support. Methods: 158 people participated in the survey, reporting pain for at least 3 months but had not received medical treatment. Data was collected at two dates: February and December 2021. Participants completed an online questionnaire due to the pandemic situation. The following six psychological questionnaires were used in the survey: Toronto Alexithymia Scale, Beck Depression Inventory 9-item version, Difficulty in Emotion Regulation Scale, Multidimensional Scale of Perceived Social Support, Chew-questions measuring health literacy, WHO Well-being Index. Results: The participants ranged from 20 to 80 years in age, of whom 140 (88%) were female. 42 participants (27%) achieved severe alexithymia. 118 people (75%) had depression, of which 72 people (46%) had mild depression, 26 (16%) had moderate depression, and 20 (13%) had severe depression. The degree of pain and alexithy-mia (r(158) = 0.16, p = 0.004), depression (r(158) = 0.41, p < 0.001), difficulties in emotion regulation (r(158) = 0.26, p = 0.004), and health literacy, and difficulties in emotion regulation (r(158) = 0.25, p = 0.001) were positively and significantly related. Conclusion: In addition to the characteristic comorbidities of people living with pain (e.g. anxiety, emotion disorder, sleep disorder), the epidemic-induced prolonged social isolation, stress and fear of illness may explain the proportion of high depression, emotion regulation difficulties or health literacy problems in the study sample which exacerbate alexithymia and the degree of pain. Based on these results it is important to draw the attention of professionals to the appropriate health care and educational needs of those affected.

A clinical study of an online educational programme for chronic pain patients.

BACKGROUND AND PURPOSE: Background - The research of alexithymia - the inability to express or understand emotions - has recently become of great importance in clinical practice, mainly in the field of doctor-patient and psychologist patient communication. Many studies have proven the correlation between alexithymia and the development of functional somatic symptoms, i.e. somatization. Purpose - The aim of this clinical study was to examine the emotion-recognition and emotion communication patterns of patients suffering from chronic pain (e.g., headache, low back pain, arthralgia, neuropathy). Moreover, the participants received access to the Hungarian adaptation of a new international online educational site (www.retrainpain.org) dealing with pain management. METHODS: Data were collected from the Headache and Chronic Pain Outpatient Clinic, Department of Neurology, Faculty of Medicine, University of Szeged, Hungary (tertiary care - Group 1) and from a general practice in district 2, Budapest, Hungary (primary care - Group 2) from March, 2017 to April, 2018. Patients received a test package containing a pain-specific questionnaire, then the Difficulties in Emotion Regulation Scale (DERS), the Toronto Alexithymia Scale (TAS-20), and the shortened Hungarian version of the WHO-Well-being (WBI-5) had to be completed. After filling out the questionnaires, all patients got access to the Hungarian adaptation of the www.retrainpain.org website. RESULTS: Altogether 92 patients participated in the study (Group 1 n=50; Group 2 n=42). Based on the TAS-20 re-sults, 35 patients reached a pathological score (≥60 points), which indicates the diagnosis of alexithymia. The mean TAS-score was lower in Group 2 (primary care) than in Group 1 (tertiary care) (p=0.003). The DERS disclosed pathological results in 19 cases (p=0.009). As regards the www.retrainpain.org chapters, we received feedback only from 25 out of 92 patients (27%) (Group 1 n=20; Group 2 n=5). CONCLUSION: Although the examined patients have been suffering from different chronic pain syndromes for years and 50% of them confirmed that symptoms placed at least moderate or heavy burden on their everyday life, the available educational programme was studied only by a smaller proportion of patients than expected. Additionally, those who surveyed the Hungarian adaptation of the www.retrainpain.org website were mainly patients from primary care (Group 2), in spite of the fact that patients from specialized medical care (Group 1) had worse subjective conditions. Our future objective is to extend our database with follow-up results and to improve patients' response willingness.

Macro- and microstructural alterations of the subcortical structures in episodic cluster headache.

Background Previous functional and structural imaging studies have revealed that subcortical structures play a key a role in pain processing. The recurring painful episodes might trigger maladaptive plasticity or alternatively degenerative processes that might be detected by MRI as changes in size or microstructure. In the current investigation, we aimed to identify the macro- and microstructural alterations of the subcortical structures in episodic cluster headache. Methods High-resolution T1-weighted and diffusion-weighted MRI images with 60 gradient directions were acquired from 22 patients with cluster headache and 94 healthy controls. Surface-based segmentation analysis was used to measure the volume of the subcortical nuclei, and mean diffusion parameters (fractional anisotropy, mean, radial and axial diffusivity) were determined for these structures. In order to understand whether the size and diffusion parameters could be investigated in a headache lateralised manner, first the asymmetry of the size and diffusion parameters of the subcortical structures was analysed. Volumes and diffusion parameters were compared between groups and correlated with the cumulative number of headache days. To account for the different size of the patient and control group, a bootstrap approach was used to investigate the stability of the findings. Results A significant lateralisation of the size (caudate, putamen and thalamus) and the diffusion parameters of the subcortical structures were found in normal controls. In cluster headache patients, the mean fractional anisotropy of the right amygdalae, the mean axial and mean diffusivity of the right caudate nucleus and the radial diffusivity of the right pallidum were higher. The mean anisotropy of the right pallidum was lower in patients. Conclusion The analysis of the pathology in the subcortical structures in episodic cluster headache reveals important features of the disease, which might allow a deeper insight into the pathomechanism of the pain processing in this headache condition.

Ipsilateral Alteration of Resting State Activity Suggests That Cortical Dysfunction Contributes to the Pathogenesis of Cluster Headache.

The pathomechanism of cluster headache (CH) is not entirely understood, but central and peripheral components were suggested. A recent report showed that transcranial magnetic stimulation measured cortical excitability was increased in the hemisphere ipsilalteral to the pain. In the current study we set out to investigate the amplitude of resting brain fMRI activity to find signatures of the increased excitability. High resolution T1 weighted and resting state functional MRI images were acquired from seventeen patients with CH in pain free period and from twenty-six healthy volunteers. Patients' data were normalized (e.g. inverted along the midsagittal axis) according to the headache side. Independent component analysis and a modified dual regression approach were used to reveal the differences between the resting state networks. Furthermore, the timecourses were decomposed into five frequency bands by discrete wavelet decomposition and were also re-regressed to the original data to reveal frequency specific resting activity maps. Two of the identified resting state networks showed alterations in CH. When the data were inverted to have patients' headaches on the left, the ipsilateral attention network showed increased connectivity in 0.08-0.04 Hz frequency band in the in CH group. In the same dataset, cerebellar network showed higher functional connectivity in 0.02-0.01 Hz range in the ipsilateral cerebellum. When the data of patients having headache on the left were inverted to the right, similar increased signal was found in the ipsilateral attention network in 0.08-0.04 Hz band. The cerebellar network showed increased connectivity in the cerebellum in 0.02-0.01 Hz band in patients. The Fourier analysis of these area revealed increased power in CH at all cases. Our results showed alterations of brain functional networks in CH. The alterations of resting state activity were found in the hemisphere ipsilateral to the pain, signifying the altered cortical processing in the pathomechanism of CH.

Interictal brain activity differs in migraine with and without aura: resting state fMRI study.

BACKGROUND: Migraine is one of the most severe primary headache disorders. The nature of the headache and the associated symptoms during the attack suggest underlying functional alterations in the brain. In this study, we examined amplitude, the resting state fMRI fluctuation in migraineurs with and without aura (MWA, MWoA respectively) and healthy controls. METHODS: Resting state functional MRI images and T1 high-resolution images were acquired from all participants. For data analysis we compared the groups (MWA-Control, MWA-MWoA, MWoA-Control). The resting state networks were identified by MELODIC. The mean time courses of the networks were identified for each participant for all networks. The time-courses were decomposed into five frequency bands by discrete wavelet decomposition. The amplitude of the frequency-specific activity was compared between groups. Furthermore, the preprocessed resting state images were decomposed by wavelet analysis into five specific frequency bands voxel-wise. The voxel-wise amplitudes were compared between groups by non-parametric permutation test. RESULTS: In the MWA-Control comparison the discrete wavelet decomposition found alterations in the lateral visual network. Higher activity was measured in the MWA group in the highest frequency band (0.16-0.08 Hz). In case of the MWA-MWoA comparison all networks showed higher activity in the 0.08-0.04 Hz frequency range in MWA, and the lateral visual network in in higher frequencies. In MWoA-Control comparison only the default mode network revealed decreased activity in MWoA group in the 0.08-0.04 Hz band. The voxel-wise frequency specific analysis of the amplitudes found higher amplitudes in MWA as compared to MWoA in the in fronto-parietal regions, anterior cingulate cortex and cerebellum. DISCUSSION: The amplitude of the resting state fMRI activity fluctuation is higher in MWA than in MWoA. These results are in concordance with former studies, which found cortical hyperexcitability in MWA.

Prophylactic Drug Treatment of Migraine in Children and Adolescents: An Update.

Migraine as a highly disabling pain condition influences the daily activities of those affected, including children and adolescents. The pathomechanism of migraine is not fully understood, and the different types of prophylactic antimigraine drugs that are applied are not specific for migraine. There is a need for preventive treatment in the event of frequent migraine attacks, an impairment of the quality of life, severe accompanying or aura symptoms, and the failure of acute drug treatment. The following pharmacological classes are recommended: antidepressants, antiepileptics, antihistamines, beta-adrenergic receptor blockers, and calcium ion channel antagonists, besides onabotulinum toxin A and nutraceuticals (butterbur). The most urgent goal as concerns pharmaceutical innovation is the development of pathomechanism-based antimigraine drugs and personalized therapy tailored to the children and adolescents.

Release of PACAP-38 in episodic cluster headache patients - an exploratory study.

BACKGROUND: Activation of the trigeminal-autonomic reflex, involving the trigeminal ganglion, the superior salivatory nucleus and the sphenopalatine ganglion (SPG) is crucial in the pathophysiology of cluster headache (CH). Since pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) is present both in the SPG and the trigeminal ganglion (TG) and its role in migraine has been described, our aim was to determine the plasma PACAP-38 levels in different phases of episodic CH (ECH). Peripheral cubital fossa blood samples were taken during the ictal and inter-bout periods of male ECH patients and from age-matched healthy controls (n = 9). Plasma PACAP-38-like immunoreactivity (LI) was measured with specific and sensitive radioimmunoassay. FINDINGS: Significantly lower plasma PACAP-38-LI was detected in the inter-bout period of ECH patients than in healthy controls. However, PACAP-38 was significantly elevated in the plasma during CH attacks as compared to the inter-bout phase in the same subjects (n = 5). CONCLUSIONS: This exploratory study suggests that PACAP-38 may be released during the attacks of ECH. Further patients and long-term follow-up are necessary to reveal its function.

[Diagnosis and treatment of stroke during pregnancy]. / A stroke diagnózisa és kezelése terhesség alatt.

Stroke, the sudden onset of brain dysfunction from a vascular cause, is one of the most common causes of long-term disability. Although rare during childbearing years, stroke is even more devastating when it occurs in a young woman trying to start a family. Pregnancy and the postpartum period are associated with an increased risk of ischemic stroke and intracerebral hemorrhage, although the incidence estimates have varied. There are several causes of stroke that are in fact unique to pregnancy and the postpartum period, such as preeklampszia and eklampszia, amniotic fluid embolus, postpartum angiopathy and postpartum cardiomyopathy. The purpose of this article is to summarize existing data regarding incidence, risk factors and potential etiologies, as well as treatment strategies for stroke in pregnancy.

[Preconceptional and perinatal challenges of pregnancy in women with epilepsy]. / Epilepsziával szövodött terhesség preconceptionalis és perinatalis kihívásai.

Reproductive-aged women with epilepsy may present a number of specific issues to be managed in daily clinical practice. The impact of epileptic seizures and antiepileptic therapy on pregnancy outcome and the risk of teratogenicity should be minimized, which require careful attention and cooperation between obstetric gynecologyst and neurologist. The aim of the present paper is to review the impact of epilepsy attack on fetus and the pathomechanism and teratogenic effect of antiepileptic drugs.

EFFECTS OF MATERNAL EPILEPSY AND ANTIEPILEPTIC THERAPY IN WOMEN DURING PREGNANCY.

OBJECTIVE: The aim of this study was to analyse the effects of epilepsy and antiepileptic drug (AED) treatment on pregnancy and the perinatal outcome, retrospectively. METHODS: We examined the obstetric and fetal outcomes among women with epilepsy (WWE), who were followed-up at the Department of Neurology, and who delivered at the Department of Obstetrics and Gynaecology (n=91) between 31th December 2000 and 31th March 2014. Statistical comparisons of different obstetric and fetal parameters on a sample of 91 WWE and 182 non-WWE were assessed by the chi-square-test, the independent sample t-test. RESULTS: The rate of major congenital malformations (MCMS) among the newborns of all AEDs exposed mothers was 7.69%. There were three peaks of seizures: during the third trimester, during delivery and in the puerperium. The prevalence of miscarriages, post-term birth and the rate of caesarean section were significantly higher among the WWE than among the non-WWE (p=0.001; p<0.001; p=0.02). Parameters of neonates (birth weight, birth length, head-, and chest circumference) were significantly different between the WWE group and the non-WWE group (p=0.003, p<0.001, p<0.001, p<0.001) CONCLUSIONS: In contrast with recent publications, there were significant differences in the parameters of neonates between the two groups. Our results are in accordance with those of previous studies from the aspect of AED-related MCM, the elevated risk of miscarriages and pre-existing hypertension.

Internet Addiction and COVID-19 Misbeliefs Among Hungarian Online Gamers: A Cross-Sectional Study.

Introduction: The internet has become a part of everyday life, and during the COVID-19 pandemic the rate of internet use has raised even higher, which increases the possibility of compulsive and problematic use leading to the acceptance of online misbeliefs and conspiration theories. This cross-sectional study aimed to explore the relationship between COVID-19-related misconceptions and internet addiction among adult recreational online gamers. Methods: A sample of 1671 recreational video game users completed the online survey (male: n = 1522 (91.08%), mean age = 21.83, SD = 4.18; female: n = 149 (8.91%), mean age = 24.33, SD = 8.38). Demographic questions, risk factors and health-related questions, internet use and addiction were measured alongside a short questionnaire about common COVID-19-related topics, such as its origin and risk of infection. Results: Out of all participants 248 (14.8%) answered all the COVID-19-related questions properly, thus having no misconceptions, while 545 (32.6%) had one wrong answer, 532 (31.8%) had 2 wrong answers, 251 (15.0%) had 3 wrong answers, 78 (4.7%) had 4 wrong answers and 17 (1.0%) had 5 wrong answers. Significant factors to a higher number of COVID-misconceptions were time spent studying (χ2 (35,1671) = 63.86, p = 0.002), marital status (χ2 (15,1671) = 30.65 p = 0.01) and secondary employment (χ2 (51,671) = 14.88, p = 0.01). Although 17.1% of the participants reached the threshold score for internet addiction, the predictors of COVID-19 misconceptions were marital status (ß = -0.06, p = 0.01) and time spent studying (ß = 0.05, p = 0.03), while neither daily internet use, internet addiction scores or risk factors predicted these misconceptions in a linear regression model. Discussion: Our study concludes that Internet addiction did not directly influence misconceptions about the COVID-19 pandemic in this population despite the surprisingly high rate of problematic users.

White matter disintegration in cluster headache.

BACKGROUND: Previous studies in primary headache disorders showed microstructural alterations in the white matter as measured by diffusion imaging. However these investigations are not in full agreement and some of those, especially in cluster headache, restricted the analysis to only a limited number of diffusion parameters. Therefore, in the current study we examined white matter microstructure in cluster headache patients. METHODS: Diffusion weighted MRI images with 60 directions were acquired from thirteen patients with cluster headache and sixteen age-matched healthy controls. Tract based spatial statistics were used to compare white matter integrity in the core of the fibre bundles. Correlation of the diffusion parameters with cumulative number of headache days was examined. RESULTS: There was a significant increment of the mean, axial and perpendicular diffusivity in widespread white matter regions in the frontal, parietal, temporal and occipital lobes. Reduced fractional anisotropy was found in the corpus callosum and some frontal and parietal white matter tracts mainly in the contralateral side of the pain. Axial diffusivity showed negative correlation to the number of the headache attacks. CONCLUSIONS: The in vivo analysis of microstructural alterations in cluster headache provides important features of the disease, which might offer a deeper insight into the pathomechanism of the disease.

[New data for the pathomechanism of neuropathic pain: therapeutic evidences]. / Új adatok a neuropátiás fájdalom patomechanizmusához: terápiás evidenciák.

The present work is based on literature data from PubMed. Neuropathic pain is caused by a lesion or disease of the somatosensory system. Peripheral and central sensitization play a crucial role in its pathomechanism. The clinical symptoms are mainly characterized by burning and throbbing pain and sensory disturbances like hyperalgesia and allodynia. Therapeutic recommendations are antidepressants, antiepileptics, opioids and neuro-stimulation methods.

Chronic Migraine as a Primary Chronic Pain Syndrome and Recommended Prophylactic Therapeutic Options: A Literature Review.

Chronic pain conditions have a high socio-economic impact and represent a burden for patients, and their management is a challenge for healthcare professionals. Chronic migraine is one of the chronic primary headache disorders, which belong to chronic primary pain syndromes as per the new concept of multiple parenting. The aims of this review were to provide an overview of the latest classification systems involving both entities, the epidemiological data, and the currently recommended prophylactic treatment options for chronic migraine. Randomized controlled clinical trials, meta-analyses, real-world data, and review articles were analyzed. Chronic migraine is a prevalent and highly burdensome disease and is associated with high headache-related disability and worsening health-related quality of life. Treatment of chronic migraine includes pharmacological or, in drug-refractory cases, non-pharmacological (e.g., neuromodulatory) approaches. Among pharmacological treatment options, injectable botulinum toxin type A and calcitonin gene-related peptide-targeting human and fully humanized monoclonal antibodies (i.e., eptinezumab, erenumab, fremanezumab, and galcanezumab) are highly recommended in the preventive treatment of chronic migraine. Novel migraine-specific therapies offer a solution for this devastating and difficult-to-treat chronic pain condition.

The pharmacotherapeutic management of episodic and chronic migraine with gepants.

INTRODUCTION: The small molecule non-peptide calcitonin gene-related peptide (CGRP) receptor antagonists named gepants offer a breakthrough novel approach in migraine acute and prophylactic drug treatment. This review aimed to determine the place of gepants in the treatment of episodic and chronic migraine. AREAS COVERED: The new generation gepants are ubrogepant, atogepant, rimegepant, and zavegepant. Ubrogepant is ratified for acute migraine treatment, atogepant is validated for preventive therapy, whereas rimegepant is ratified for both indications, all via oral administration and while zavegepant is administered intranasally for migraine attacks. Gepants are effective, safe, and well-tolerated in acute or prophylactic therapy. The PubMed literature search included randomized controlled trials, meta-analyses, real-world data, and review articles published in English until January 2023. EXPERT OPINION: Whether gepants will be real game changers in the acute treatment of migraine compared to triptans and ditans or in the prophylactic therapy compared to standard-of-care preventive drugs or CGRP-targeting monoclonal antibodies cannot be answered yet based on the available literature data.