Non-Pharmacological Treatment for Chronic Migraine.

PURPOSE OF REVIEW: Chronic migraine (CM) affects a large proportion of the population and is a significant source of disability and lost productivity. Numerous non-pharmacological approaches have been attempted during the past decades. This review discusses the most recent and evidence-based advances in acute and preventive non-pharmacological therapeutic approaches for CM, offering alternatives to drug treatment. RECENT FINDINGS: A growing number of non-pharmacological treatment options, including non-invasive or invasive neuromodulation, acupuncture, psychotherapy, and physiotherapy, have shown promising efficacy in CM. There is strong evidence for the effectiveness of non-invasive neuromodulation such as transcranial magnetic stimulation, transcranial direct current stimulation, and transcutaneous electrical nerve stimulation (TENS) in CM, but less evidence for approaches such as invasive neuromodulation, physical therapy, or dietary approaches. Acupuncture for migraine remains controversial, with the main point of contention still being the placebo effect. Non-pharmacological approaches can be offered as a reliable alternative for patients with CM, and more research is being done to evaluate the efficacy of non-invasive neuromodulation with different parameters and the combination of different treatments in CM.

Abnormal Thalamo-Cortical Interactions in Overlapping Communities of Migraine: An Edge Functional Connectivity Study.

OBJECTIVE: Migraine has been demonstrated to exhibit abnormal functional connectivity of large-scale brain networks, which is closely associated with its pathophysiology and has not yet been explored by edge functional connectivity. We used an edge-centric approach combined with motif analysis to evaluate higher-order communication patterns of brain networks in migraine. METHODS: We investigated edge-centric metrics in 108 interictal migraine patients and 71 healthy controls. We parcellated the brain into networks using independent component analysis. We applied edge graph construction, k-means clustering, community overlap detection, graph-theory-based evaluations, and clinical correlation analysis. We conducted motif analysis to explore the interactions among regions, and a classification model to test the specificity of edge-centric results. RESULTS: The normalized entropy of lateral thalamus was significantly increased in migraine, which was positively correlated with the baseline headache duration, and negatively correlated with headache duration reduction following preventive medications at 3-month follow-up. Network-wise entropy of the sensorimotor network was significantly elevated in migraine. The community similarity between lateral thalamus and postcentral gyrus was enhanced in migraine. Migraine patients showed overrepresented L-shape and diverse motifs, and underrepresented forked motifs with lateral thalamus serving as the reference node. Furthermore, migraine patients presented with overrepresented L-shape triads, where the postcentral gyrus shared different edges with the lateral thalamus. The classification model showed that entropy of the lateral thalamus had the highest discriminative power, with an area under the curve of 0.86. INTERPRETATION: Our findings indicated an abnormal higher-order thalamo-cortical communication pattern in migraine patients. The thalamo-cortical-somatosensory disturbance of concerted working may potentially lead to aberrant information flow and deficit pain processing of migraine. ANN NEUROL 2023;94:1168-1181.

Dynamic changes in CGRP, PACAP, and PACAP receptors in the trigeminovascular system of a novel repetitive electrical stimulation rat model: Relevant to migraine.

Migraine is the seventh most disabling disorder globally, with prevalence of 11.7% worldwide. One of the prevailing mechanisms is the activation of the trigeminovascular system, and calcitonin gene-related peptide (CGRP) is an important therapeutic target for migraine in this system. Recent studies suggested an emerging role of pituitary adenylate cyclase-activating peptide (PACAP) in migraine. However, the relation between CGRP and PACAP and the role of PACAP in migraine remain undefined. In this study, we established a novel repetitive (one, three, and seven days) electrical stimulation model by stimulating dura mater in conscious rats. Then, we determined expression patterns in the trigeminal ganglion and the trigeminal nucleus caudalis of the trigeminovascular system. Electrical stimulation decreased facial mechanical thresholds, and the order of sensitivity was as follows: vibrissal pad >inner canthus >outer canthus (P < 0.001). The electrical stimulation group exhibited head-turning and head-flicks (P < 0.05) nociceptive behaviors. Importantly, electrical stimulation increased the expressions of CGRP, PACAP, and the PACAP-preferring type 1 (PAC1) receptor in both trigeminal ganglion and trigeminal nucleus caudalis (P < 0.05). The expressions of two vasoactive intestinal peptide (VIP)-shared type 2 (VPAC1 and VPAC2) receptors were increased in the trigeminal ganglion, whereas in the trigeminal nucleus caudalis, their increases were peaked on Day 3 and then decreased by Day 7. PACAP was colocalized with NEUronal Nuclei (NeuN), PAC1, and CGRP in both trigeminal ganglion and the trigeminal nucleus caudalis. Our results demonstrate that the repetitive electrical stimulation model can simulate the allodynia during the migraine chronification, and PACAP plays a role in the pathogenesis of migraine potentially via PAC1 receptor.

Migraine Prevention Using Different Frequencies of Transcutaneous Occipital Nerve Stimulation: A Randomized Controlled Trial.

This study's objective was to evaluate the efficacy and tolerability of transcutaneous occipital nerve stimulation (tONS) in patients with migraine, and to explore whether different tONS frequencies influenced treatment effectiveness. This was a randomized, controlled trial of tONS for prevention of migraine. Patients were randomized to 1 of 5 therapeutic groups before treatment for 1 month. Groups A through C received tONS at different frequencies (2 Hz, 100 Hz, and 2/100 Hz), group D underwent sham tONS intervention, and group E received topiramate orally. The primary outcomes were the 50% responder rate and headache characteristics. A total of 110 patients completed the study. The 50% responder rate was significantly greater in the groups undergoing active tONS and topiramate, compared with sham-treated group. A significant reduction in headache intensity was noted in each test group compared with the sham group; the groups undergoing tONS at different frequencies did not differ significantly. From baseline to the 1-month treatment period, the tONS group with 100 Hz and topiramate group exhibited significant decreases in headache duration. We conclude that tONS therapy is a new promising approach for migraine prevention. It has infrequent and mild adverse events and may be effective among patients who prefer nonpharmacological treatment. PERSPECTIVE: This article introduces a randomized, controlled trial to illustrate tONS as a new approach for prevention of migraine. It shows tONS is well tolerated and could be considered as a promising treatment for patients who prefer to nonpharmacological therapy.