Mohammad Al-Mahdi Al-Karagholi

Danish Institute for Health Services Research · Danish headache center

Background Adenosine is a purinergic signaling molecule with a wide range of physiological functions including anti- and pronociceptive properties. Adenosine receptors are expressed in the trigeminovascular system, and adenosine receptor antagonist, caffeine, relieves migraine headache. We performed a systematic review of the literature of preclini...

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 rev...

Migraine is a common disabling disease with a complex pathophysiology. Headache is a frequent side effect after intravenous adenosine administration, while adenosine receptor antagonist, caffeine, relieves migraine headache. These observations suggest a possible involvement of adenosine signaling in headache and migraine pathophysiology.In a random...

Migraine is a common, neurovascular headache disorder with a complex molecular interplay. The involvement of ion channels in the pathogenesis of migraine gathered considerable attention with the findings that different ion channels subfamilies are expressed in trigeminovascular system, the physiological substrate of migraine pain, and several ion c...

Background The present case contributes to the limited literature on central nervous system involvement of blastic plasmacytoid dendritic cell neoplasm (BPDCN). Case presentation A 63-year-old male presented to the department of neurology with a three-day history of rapidly progressing headache, fatigue, and confusion. Physical examination revea...

A 30-year-old male diagnosed three years previously with reversible cerebral vasoconstriction syndrome (RCVS) presented to the department of neurology with an accumulation of attacks mimicking previous RCVS attacks and fulfilling the diagnostic criteria for RCVS after receiving the first Pfizer COVID-19 vaccine. The neurologic exam, blood samples,...

Introduction The activation of perivascular fibers and the consequent release of vasoactive peptides, including the vasoactive intestinal polypeptide (VIP), play a role in migraine pathogenesis. A 2-h infusion of VIP provoked migraine, but the mechanisms remain unknown. We investigated whether 2-h infusion of VIP caused alterations in plasma levels...

Objective: To determine whether glibenclamide, a non-selective adenosine 5'-triphosphate-sensitive K+ (KATP) channel blocker, attenuates pituitary adenylate cyclase-activating polypeptide-38 (PACAP38)-induced headache and vascular changes in healthy volunteers. Methods: In a double-blind, randomized, placebo controlled and crossover design, 22 h...

Objective: To systematically review clinical studies investigating the involvement of adenosine and its receptors in migraine pathophysiology. Background: Adenosine is a purinergic signaling molecule, clinically used in cardiac imaging during stress tests. Headache is a frequent adverse event after intravenous adenosine administration. Migraine...

Background To describe and discuss the association between COVID-19 vaccination and RCVS attacks in a patient with RCVS and whether targeting angiotensin 2 receptor could be a preventive option. Case presentation A 30-year-old male previously diagnosed with reversible cerebral vasoconstriction syndrome (RCVS), presented to the department of neurol...

Glucagon-like-peptide-1 (GLP-1) is an incretin hormone implicated in several metabolic and neurological disorders. GLP-1 induces vasodilation and increases blood flow in the peripheral circulation. Whether GLP-1 alters cerebral hemodynamics in humans is yet to be elucidated. In a crossover, double-blind, placebo-controlled, and randomized design, 2...

Background Structural imaging has revealed changes in cortical thickness in migraine patients compared to healthy controls is reported, but presence of dynamic cortical and subcortical changes during migraine attack versus inter-ictal phase is unknown. The aim of the present study was to investigate possible changes in cortical thickness during spo...

Importance Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptides (PACAPs) are structurally and functionally related, yet different in their migraine-inducing properties. It remains unclear whether the lack of migraine induction can be attributed to the only transient vasodilatory response after a 20-minute...

Background Calcitonin gene-related peptide (CGRP) dilates cranial arteries and triggers headache. The CGRP signaling pathway is partly dependent on activation of ATP-sensitive potassium (K ATP ) channels. Here, we investigated the effect of the K ATP channel blocker glibenclamide on CGRP-induced headache and vascular changes in healthy volunteers....

Background Structural imaging has revealed changes in cortical thickness in migraine patients compared to healthy controls is reported, but presence of dynamic cortical and subcortical changes during migraine attack versus inter-ictal phase is unknown. The aim of the present study was to investigate possible changes in cortical thickness during spo...

Objective To determine whether the intravenous infusion of adrenomedullin, a potent vasodilator belonging to calcitonin family of peptides, provokes attacks of migraine in patients. Methods Twenty migraine without aura patients participated in a placebo-controlled and double-blinded clinical study. In a randomized and crossover design the patients...

Migraine afflicts more than one billion individuals worldwide and is a leading cause of years lived with disability. In about a third of individuals with migraine aura occur in relation to migraine headache. The common pathophysiological mechanisms underlying migraine headache and migraine aura are yet to be identified. Based on recent data, we hyp...

The kynurenine pathway (KP) is the main path for tryptophan metabolism, and it represents a multitude of potential sites for drug discovery in neuroscience, including pain, stroke, and epilepsy. L-kynurenine (LKYN), the first active metabolite in the pathway, emerges to be a prodrug targeting glutamate receptors. The safety, tolerability, pharmacok...

Migraine is a disabling neurological disorder, diagnosis of which is based on clinical criteria. A shortcoming of these criteria is that they do not fully capture the heterogeneity of migraine, including the underlying genetic and neurobiological factors. This complexity has generated momentum for biomarker research to improve disease characterisat...

Objective Migraine is a prevalent and disabling neurological disease. Its genesis is poorly understood and there remains unmet clinical need. We aimed to identify mechanisms and thus novel therapeutic targets for migraine using human models of migraine and translational models in animals, with emphasis on amylin, a close relative of calcitonin gene...

Migraine is a common and frequently disabling neurological disorder, but the initiating migraine mechanisms are still poorly understood. Potassium channel opening may cause migraine, and we therefore examined the migraine-inducing effect of MaxiPost, a large (big)-conductance calcium-activated potassium (BKCa) channel opener, on migraine induction...

Objective: To determine whether early treatment with sumatriptan can prevent PACAP38-induced migraine attacks. Methods: A total of 37 patients with migraine without aura were enrolled between July 2018 to December 2019. All patients received an intravenous infusion of 10 picomole/kg/min of PACAP38 over 20 min followed by an intravenous infusion...

Background: Erenumab has recently been approved as a pharmacological treatment for the prevention of migraine. However, the incidence estimates of adverse drug reactions (ADRs) were not consistent among studies. Consequently, pooled measures of the incidences of ADRs that accounts for inter-study heterogeneity are desirable. In addition, little is...

Purpose of Review Migraine remains a challenging condition to treat, thus highlighting the need for a better understanding of its molecular mechanisms. This review intends to unravel a new emerging target in migraine pathophysiology, the adenosine 5′-triphosphate-sensitive K⁺ (KATP) channel. Recent Findings KATP channel is a common denominator in...

Background Human models of migraine have been used for the past 30 years to test putative ‘trigger’ molecules and ascertain whether they induce migraine attacks in humans. However, nocebo effects using this model have never been systematically explored. Objective To assess the nocebo response rate in randomised clinical trials conducted at the Dan...

Glibenclamide inhibits sulfonylurea receptor (SUR), which regulates several ion channels including SUR1-transient receptor potential melastatin 4 (SUR1-TRPM4) channel and ATP-sensitive potassium (K ATP ) channel. Stroke upregulates SURl-TRPM4 channel, which causes a rapid edema formation and brain swelling. Glibenclamide may antagonize the formatio...

Introduction Preclinical data implicate large conductance calcium-activated potassium (BK Ca ) channels in the pathogenesis of headache and migraine, but the exact role of these channels is still unknown. Here, we investigated whether opening of BK Ca channels would cause headache and vascular effects in healthy volunteers. Methods In a randomized...

Introduction Administration of ATP-sensitive potassium channel opener levcromakalim triggers headache in healthy volunteers and migraine attacks in migraine patients. Here, we investigated the effect of ATP-sensitive potassium channel blocker glibenclamide on levcromakalim-induced headache in healthy volunteers. Methods In a randomized, double-bli...

Lanfranco Pellesi,1 Roberto De Icco,2,3 Mohammad Al-Mahdi Al-Karagholi,1 Messoud Ashina1,4 1Danish Headache Center, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; 2Headache Science Center, IRCCS Mondino Foundation, Pavia, Italy; 3Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy;...

Background In recent years, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptides (PACAPs) have gained special interest in headache science. VIP and PACAPs (two isoforms, PACAP27 and PACAP38) are related in structure and function, as are their receptors, but they show differences in vasodilating- and headache-i...

Background: Pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) induces headache in healthy volunteers but the precise mechanisms by which PACAP38 leads to headache are unclear. We investigated the headache preventive effect of sumatriptan and ketorolac on PACAP38-induced headache in healthy volunteers. In addition, we explored contrib...

Large (big)-conductance calcium-activated potassium (BKCa) channels are expressed in migraine-related structures such as the cranial arteries, trigeminal ganglion and trigeminal spinal nucleus, and they play a substantial role in vascular tonus and neuronal excitability. Using synthetic BKCa channels openers was associated with headache as a freque...

Introduction Levcromakalim opens ATP-sensitive potassium channels (K ATP channel) and induces head pain in healthy volunteers and migraine headache in migraine patients, but no pain in other parts of the body. K ATP channels are expressed in C- and Aδ-fibers, and these channels might directly activate nociceptors and thereby evoke pain in humans....

Objective To systematically review the vascular effects of glibenclamide. Background Infusion of adenosine triphosphate (ATP)-sensitive potassium (K ATP ) channel opener (KCO) levcromakalim dilates cranial arteries and induces headache and migraine attacks. Recent data show that levcromakalim-induced vasodilation is associated with headache. Glibe...

Background: ATP-sensitive potassium (KATP ) channel opener levcromakalim induces migraine attacks in migraine patients. Underlying mechanisms responsible for headache and migraine induction after levcromakalim infusion are unknown. Objective: To investigate the effect of levcromakalim on the cranial arteries and to explore the possible relations...

Introduction Non-invasive vagus nerve stimulation (nVNS; gammaCore®) has the potential to prevent migraine days in patients with migraine on the basis of mechanistic rationale and pilot clinical data. Methods This multicentre study included a 4-week run-in period, a 12-week double-blind period of randomised treatment with nVNS or sham, and a 24-we...

Pituitary adenylate cyclase-activating polypeptide (PACAP) has emerged as an important signaling peptide in migraine pathogenesis. Recently, we have shown that the less-abundant PACAP isoform, PACAP27, induced migraine and headache in patients equipotently to PACAP38. The present study examined the effect of PACAP27 on cerebral hemodynamics in heal...

Introduction Pituitary adenylate cyclase-activating polypeptide (PACAP) is found in two functional isoforms, namely PACAP38 and PACAP27. The migraine-inducing properties of PACAP38 are well studied. However, it is not known whether the lesser-known and under-studied protein isoform, PACAP27, can also induce migraine attacks. Here, we studied the ef...

Migraine is one of the most disabling and prevalent of all disorders. To improve understanding of migraine mechanisms and to suggest a new therapeutic target, we investigated whether opening of ATP-sensitive potassium channels (KATP) would cause migraine attacks. In this randomized, double-blind, placebo-controlled, crossover study, 16 patients age...

Background To review the distribution and function of KATP channels, describe the use of KATP channels openers in clinical trials and make the case that these channels may play a role in headache and migraine. Discussion KATP channels are widely present in the trigeminovascular system and play an important role in the regulation of tone in cerebra...