Advances in the Management of Acute Treatment of Migraine - Episode 9

Role of Neuromodulation for Acute Treatment of Migraine

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Current devices and mechanisms available for neuromodulation for acute treatment of migraine.

Peter J. Goadsby, MD, PhD: We’re going to transition to the next section. In this section, we’re going to be talking about neuromodulation. Neuromodulation has been the poor cousin of pharmaceutical development because the beauty of a specific receptor is that you can talk about it and you have a target. Neuromodulation is a step back because it effectively takes advantage of nerve neurotransmitter change in a much broader fashion. It’s much harder to design good-quality clinical trials because of the nature of the stimulus and the problem of unblinding. 

That said, we’ve had progress, and things are available. Jelena, can you set out some of the things physicians might be interested in regarding neuromodulation? 

Jelena Pavlovic, MD, PhD: Sure, Peter. As you said, the question is, can we manipulate central and peripheral pain pathways? Can we use ways to modulate the activity of nerve pathways? There are attractive alternatives, though they have been a stepchild to the medication revolution that we have had in the past few years. They’re quite attractive because it is hard for us to predict which patients will be most responsive to various medical treatments. 

Given the adverse effects, comorbidity profiles, and so on, it is very attractive to have a treatment that presumably doesn’t have adverse effects and can be used with many comorbidities of migraine. It is also useful in patients who are worried about medication overuse in headache, specifically with triptans and even with lasmiditan, with which there’s a warning that there may be that potential. 

With gepants, we don’t think there is, but at this point we don’t have enough evidence to fully assess that. The overall goals of neurostimulation can be summarized in 3 parts. One goal is to wind down the central sensitization that we know drives migraine. Another is to block processes for attack duration. The third is to enhance pain inhibitory networks, so potentiating. Inhibiting networks, downplaying the central sensitization, and preventing propagation of attack are the goals of neurostimulation. 

We have 3 principal devices that have been studied and have FDA approval for migraine. The first is transcutaneous supraorbital neurostimulation. Simply put, that is the stimulation of the supratrochlear supraorbital branches of the trigeminal nerve. It is a device that’s placed right here. It works by modulating trigeminal nerve nociception and gradual neuromodulation of central pain processing areas. 

There have been several trials of it. They’re relatively small, and as you mentioned, there’s an issue with devising a good sham control, because the feeling is electrical. It’s a small stimulus, which a majority of patients tolerate quite well, but there are patients who cannot tolerate it, particularly patients who tend to have chronic allodynia in that area. It does have a good safety profile, but some patients do report such things as fatigue and insomnia. Very rarely, some patients have reported activation of headache and worsening of local pains and paresthesia. 

That’s something to be aware of, and it’s contraindicated in patients who have metal implants or electronic devices in their heads. It is also contraindicated in patients with cardiac defibrillators and pacemakers. I don’t know if I mentioned that in the United States, it was first approved as a preventive treatment for migraine. Currently, it is approved as both treatment for acute and chronic migraine, and the same device can have both modes of treatment. 

The second device of interest is the noninvasive vagal nerve stimulation, which is a device that’s placed over the area of the vagus nerve in the neck. It has received FDA approval for both acute and preventive treatment of migraine and also for episodic cluster headache, in which it has some interesting data. What is good is that while the supratrochlear and supraorbital stimulation takes at least 20 minutes for preventive and acute treatment, the acute treatment via stimulation of the vagus nerve is 2 minutes. That can be repeated after 20 minutes and 2 hours as needed. The preventive treatment is 2 minutes, 3 times a day. 

The mechanism of action is possibly to decrease glutamate and suppress neuronal firing in the trigeminal cervical complex, as with everything else. It also further modulates the trigeminal autonomic reflex through the vagus nerve. There are contraindications in people who have implanted medical devices, especially metallic devices in the neck. Carotid atherosclerosis, which generally happens in older patients, a history of cervical vagotomy, significant hypertension, and bradycardia are also contraindications. 

Finally, the most recently approved neurostimulation mechanism is the remote electrical neuromodulation, which is a placement of an electrical stimulus on the deltoid area of the upper arm. It’s a single 45-minute treatment within 1 hour of migraine onset. 

All the publication materials from the manufacturer make it look like the most relaxing migraine attack ever. The mechanism of action is believed to be through a conditioned pain modulation by stimulating C- and A-delta nociceptive sensory fibers in the upper arm and musculoskeletal nerves. That stimulation then activates descending pain inhibitory pathways that originate in the periaqueductal gray and rostroventromedial medulla. That down-regulates the activation of the trigeminal cervical complex. 

Peter J. Goadsby, MD, PhD: We have quite a range of options and some detailed understanding.

Jelena Pavlovic, MD, PhD: Yes, and how long we have had these treatments available to us varies. The supraorbital neurostimulation has been available for the longest time. I would say that most of us have had the most extensive experience with it. The transcutaneous option is somewhat newer. It was FDA approved more recently, so there is somewhat limited experience with it.