Neuromodulation for Migraine

Professor Stephen Silberstein

Professor, Director of the Headache Center, Thomas Jefferson University

Prof. Silberstein completed his medical degree at the University of Pennsylvania and finished his medical internship at the National Institutes of Health (NIH). During his neurology residency, he found himself happier when working at a free clinic and taking care of patients, so he decided that his role was in clinical medicine and making it better. He got particularly interested in headache medicine and he devoted his entire career to this area. He eventually moved from private practice to academic practice and he is currently the director of the Headache Center at Thomas Jefferson University Hospitals.

How Common Is It and How Complex Is the Diagnosis of Migraine?

If you got a cold or the flu, you’re going to get a headache as a side effect or “secondary headache”. But if you have an event where you have head pain that throbs, you feel sick to your stomach – the overwhelming odds are that it’s migraine. A headache that keeps you from doing things more often than not is a migraine and a low-grade mild headache usually is a tension headache. Most of the other headache types, like secondary to another medical illness, are very rare. So it’s not that hard to diagnose migraines if you say it’s a disabling headache and life bothers you or you’re sick to your stomach, as opposed to trying to get every single piece of the puzzle together. One of my friends did a study in a GP’s office, and they found out that 90% of the patients who come with a headache complaint, do in fact have a migraine. If you think about it, 12% of the population of the United States have a migraine.

How Did We Arrive at Using Neuromodulation as a Treatment for Headaches?

If we go back 2,000 years, one of the physicians from the roman theatres, took a live torpedo, put it on the head and shot his head to make headaches go away. So neuromodulation has been around for a long time and with the development of electricity, there’s electroshock therapy, which eventually led to an interesting observation. There were patients who had intractable epilepsy who had an implanted vagal nerve stimulator, and those patients who had it their headaches got better. There were also people with “occipital neuralgia” who had implants, and their migraine headaches got better. 

So it began that way, and it led to the development of non-invasive vagal nerve stimulation, which stimulates the vagus nerve. There are multiple different devices for this stimulation. There’s a device that fits on the forehead, called the cephalic device, that stimulates like tens unit the nerves. This led to the development of auricular vagal nerve stimulator and to the ceramic device which fits on the arm and stimulates it. There’s also another device that just came back, which is a magnetic stimulator that stimulates the brain’s surface. There is also a sphenopalatine ganglion stimulator that I believe has just come back to treat cluster headaches. So there’s a lot of different approaches for neuromodulation; all are different, but what they are really doing is changing the behaviour of the brain and the pain pathways.

What Are the Principles Underlying Neuromodulation for the Treatment of Pain?

Let me give you an example. have you ever stubbed your toe and then massage your leg? This is called “conditioned pain modulation”, information from the other side goes up into the brain stem and turns off the descending pain control system in your leg. One of the tricks I’ve learned is when I go to a dentist, which I find very uncomfortable, I take my nail and put it against the finger to create a semi-painful stimulus, and I don’t feel what the dentist is doing – that’s called conditioned pain modulation. The second principle of the tens unit is that you stimulate with a low frequency in the same area of the pain, and by the principle that pain inhibits pain at the same spinal cord or brain stem level, it turns the pain off locally. Vagal nerve stimulation is a different principle; the information goes into the brain, the vagus is quieting parasympathetic, which shuts off the whole chain reaction of pain-relieving things.

What Is a Medication-Induced Headache and Is There an Equivalent for Neuromodulation?

There’s something called analgesic induced or medication overuse headache. If you take too much of certain drugs or medicines, as they wear off the headache comes back. That’s a drug-induced or medication headache. It’s not the analgesic itself, it’s the fact that you’ve taken so much of it that you become used to it, and you need to keep taking it. The interesting thing about neuromodulation is that it doesn’t do the same thing. You use neuromodulation – the more you use it, it acts as prevention, keeps headaches from occurring and doesn’t produce withdrawal headaches. However, we know from some of the basic science work, that if you have electrical stimulation, it changes the neurochemicals inside of the brain and that if you give it repeatedly, it can act quite the entire system down.

How Much Personalisation Does Vagal Stimulation Require for Optimal Therapeutic Effect?

If you look at invasive stimulation, like occipital nerve stimulation, it has to be fine-tuned for the patient. In the cephalic device, you have the ability to increase the volume up and down on a personal level. Same with the vagus nerve stimulation and the ceramic device. But many of the devices have a “volume control frequency and duration” – everything of the impulse is fixed. Still, skin resistance is different in people and the same volume may produce more input. So you can all adjust it on an individual basis, but the shape of the waveform and the duration are fixed. All of these waveforms have been tested and checked in animal models to get the optimal form. That’s what we know.

We also know that you can actually do the opposite by modifying the waveform to prevent it from working. I’ve learned a lot about it – I used to think that a slow up and a slow down would be better, but the people who are in physics sharp up and down, because you need a certain level of activity. Also, if you’re an electroneurophysiologist, you know the best waveform to get an impulse and specifically stimulate the nerve types you want. So my point of view and my bias is that people who’ve invented these devices have found that the only thing you need to do is adjust the intensity, not the waveform.

When you change the waveform – if you’re doing a clinical trial, for example, you adjust the waveform to a point where you can feel it, but it doesn’t do anything positive for you. I’m pretty impressed with that, and I think that with the invasive dry lysis it’s a different animal. You’re actually in tissue, and what surrounds the electrodes is probably important and not as stable as applying an external device. That’s been my practical experience with doing both invasive and non-invasive. Invasive devices need to be individually adjusted because they’re not an atmosphere of moisture and tissue.

The Big Changes on the Horizon for Neuromodulation for Headache

An important point is miniaturisation of devices. However, the most important one from a public health point of view is to let or make insurance companies pay for these devices. For example, we now have tablets for the treatment of migraine, and it costs about a hundred dollars a pill. You can buy the ceramic device for 12 treatments for the same amount. The question really is, that we need to be able to give the right device to the right patient for the right reason. Until that happens, we’re not going to get anybody better.

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