Treating Chronic Migraine With Neuromodulation: The Role of Neurophysiological Abnormalities and Maladaptive Plasticity

Abstract

Chronic migraine (CM) is the most disabling form of migraine, because pharmacological treatments have low efficacy and cumbersome side effects. New evidence has shown that migraine is primarily a disorder of brain plasticity and migraine chronification depends on a maladaptive process favoring the development of a brain state of hyperexcitability. Due to the ability to induce plastic changes in the brain, researchers started to look at Non-Invasive Brain Stimulation (NIBS) as a possible therapeutic option in migraine field. On one side, NIBS techniques induce changes of neural plasticity that outlast the period of the stimulation (a fundamental prerequisite of a prophylactic migraine treatment, concurrently they allow targeting neurophysiological abnormalities that contribute to the transition from episodic to CM. The action may thus influence not only the cortex but also brainstem and diencephalic structures. Plus, NIBS is not burdened by serious medication side effects and drug–drug interactions. Although the majority of the studies reported somewhat beneficial effects in migraine patients, no standard intervention has been defined. This may be due to methodological differences regarding the used techniques (e.g., transcranial magnetic stimulation, transcranial direct current stimulation), the brain regions chosen as targets, and the stimulation types (e.g., the use of inhibitory and excitatory stimulations on the basis of opposite rationales), and an intrinsic variability of stimulation effect. Hence, it is difficult to draw a conclusion on the real effect of neuromodulation in migraine. In this article, we first will review the definition and mechanisms of brain plasticity, some neurophysiological hallmarks of migraine, and migraine chronification-related (dys)plasticity. Secondly, we will review available results from therapeutic and physiological studies using neuromodulation in CM. Lastly we will discuss the results obtained in these preventive trials in the light of a possible effect on brain plasticity.

Cathodal tDCS Guided by Thermography as Adjunctive Therapy in Chronic Migraine Patients: A Sham-Controlled Pilot Study

“…Also, we applied a extracephalic montage, instead of cephalic, which limits the confounding factors related to the stimulation of different brain areas (35). In addition, outside the motor cortex, the excitatory or inhibitory effects of anodal and cathodal tDCS are debatable (7).…”

“…tDCS is not the only NIBS technique applied in migraine. Repetitive transcranial magnetic stimulation (rTMS) was applied in large trials with encouraging results [for review, see (7)]. However, other potential targets may be taken into account, such as Non-invasive Vagus Nerve Stimulation [nVNS, (36)], Transcutaneous Supraorbital and Occipital Electrical Neurostimulation [tSNS and tONS, (37,38)], as well as the cerebellum (39).…”

“…In particular, recent data suggest that migraine is characterized, at the network level, by metaplasticity-like mechanisms that, grounding on abnormal cortical excitability, lead to defective long-term potentiation (LTP) and longterm depression (LTD) mechanisms (5). For this reason in the last decade there has been an increasing interest for non-invasive brain stimulation (NIBS) techniques inducing excitability changes for migraine treatment (6,7), which have been shown to produce metaplasticity-like patterns in migraine patients (5) and in visual cortex and associative areas (8).…”

“…Both monocephalic (active electrode on the scalp, reference electrode on the shoulder) and bicephalic (both electrodes on the scalp) were used, in different locations, such as anodal stimulation on V1 (16), anodal stimulation on M1 (17), frontal anodal stimulation (18), anodal stimulation on chronic pain affected patients (19). The available evidence on migraine patients is currently limited by the number of subjects treated (7,17,(20)(21)(22) In addition, both single-application settings and multiple-application settings were tested, thus introducing another bias that prevents from a full comparability between the study results (15).…”

The fifth cranial nerve in headaches

“…The initial use of VNS to treat headaches first came from the epilepsy field, following several anecdotal reports of migraine improvement in patients with comorbid epilepsy who had been implanted with the device [205]. The vagal nerve is a mixed motor and sensory nerve that is important in controlling autonomic responses; it projects to several higher centres that are important in pain regulation [108].…”