TRANSCRIPT

Molly O’Brien: Hello, and welcome to Spotlight on Migraine. I am your host, Molly O’Brien. Today, we are discussing migraine and neck pain. Is neck pain a symptom or a cause of a migraine attack? To help us answer this question and many more, I’d like to welcome our guest, Dr. Richard Lipton. Dr. Lipton is a neurologist and an epidemiologist with a longstanding interest in migraine. He is the Edwin S. Lowe professor and vice chair of neurology, professor of epidemiology and population health, and professor of psychiatry and behavioral sciences at the Albert Einstein College of Medicine. He’s practiced headache medicine for more than 30 years and has directed the Montefiore Headache Center for 2 decades. Dr. Lipton, thank you for joining us.

Richard Lipton, MD: I’m very happy to be here.

O’Brien: So when we’re talking about neck pain and migraine, is neck pain a cause of migraine, or is it an effect of a migraine attack, or both?

Lipton: Yeah, so it really can be both. So neck pain is one of the most common features associated with migraine. The migraine attack is divided into four phases – the prodrome, the aura, the headache phase, and the postdrome. So the prodrome is a set of warning symptoms that let people know that headache pain is coming. And perhaps 60% of people with migraine have neck pain as a warning symptom of impending headache, and about the same number continue to have neck pain after the headache begins. 

And in that context, the neck pain is actually a manifestation of migraine. And we know very well how the anatomy of that works, because the nerves that mediate pain from the neck and the nerves that mediate pain from the back of the head converge at the base of the brain in an area called the brainstem. And then the lines that go up into the brain to give us the conscious experience of pain converge. So if what you have is migraine pain, you can sometimes first experience that in the neck, and neck pain is often a manifestation of migraine.

On the other hand, if you activate the nerves at the back of the head – like, let’s say you have disease in your cervical spine, or let’s say you have disease of the nerves at the back of the head that are called the occipital nerves – input from those nerves can lower the threshold for having migraine and make your migraine attacks more frequent and more severe. 

So the challenge is to figure out really is neck pain part of the migraine attack, or is neck pain a symptom of a different disorder that may make migraine worse?

O’Brien: And with that, how do we tell?

Lipton: The best approach is based on the timing of the neck pain. So if the neck pain comes as a warning, say, within 24 hours that the headache is coming, or if the neck pain always comes with migraine, then chances are the neck pain is actually a feature of migraine. And that’s really very common. If on the other hand, you have ongoing neck pain, or neck pain that’s triggered by head turning or extending your neck, then that could be a separate feature which may still be an exacerbating factor for migraine. 

And the reason it’s important is many physicians who don’t recognize neck pain as a manifestation of migraine may order MRIs of the spine when there’s no symptom coming from the spin and may even do interventions directed to the spine which don’t really help much for migraine. On the other hand, if there is a problem in the neck, addressing the neck problem can be extremely helpful if it’s making migraine more frequent or more severe. 

The other thing I’ll point out. There was a recent study called the PRODROME study, where for a 2-month period we had people keep diaries where they would write down if they thought a headache was coming and how they knew, and then whether or not the headache came. And we found a large group of people for whom the onset of headache was very predictable, and we found that neck pain was one of the strongest predictive features of impending headache. 

We then took those people and put them in a randomized trial where they treated one attack with a drug called ubrogepant, and treated the next attack with placebo, or vice versa. And we showed that in people who have neck pain or other warning symptoms, treating with ubrogepant actually prevents headache. So it’s also important, because if neck pain regularly heralds the onset of your headache, you can use that as a clue to give yourself early treatment and prevent the headache from coming on altogether. 

O’Brien: Let’s talk a little bit more about neck pain as a symptom of migraine, or kind of a precursor to the headache portion of the attack coming. You mentioned that it’s fairly common. But do we know if anyone is actually more likely to have that neck pain as a symptom of migraine, and if that’s the case why do we know?

Lipton: The fact that people with migraine so often have neck pain is a reflection of the normal anatomy that even people who don’t have migraine have. And why it is that most people with migraine have neck pain, but some people don’t? I really don’t know. We know that neck pain travels with a set of migraine features. So we did a study called CaMEO-I, where we looked at people who had migraine with neck pain and people who had migraine without neck pain. And we found those with neck pain had more frequent, more severe, more disabling attacks, and greater reduction in health-related quality of life on the one hand.

And on the other hand, if you pick any migraine features – migraine with nausea, migraine with aura – and you ask how do people who have migraine with aura and migraine without aura compare? If you have aura you also have more severe migraine. 

So it may just be that the more symptoms you have the worse you do. We’re not really sure. But certainly, the group with neck pain does suffer more and has more frequent attacks, more severe attacks, and more disability than those who don’t have neck pain. 

O’Brien: It’s really interesting to note that. And I also think that’s really good context that you provided, just reading the study. I hadn’t really thought of that, that most people with more symptoms are probably going to experience the disease in a more severe state. That makes a lot of sense. And I think the context is important, that we’re not just looking at it from the scope of if you have migraine and you have neck pain, everything’s worse. So that’s really important context.

I want to talk a little bit more about some of those findings from the CaMEO-I study, and you looked specifically at neck pain with headache. Can you just tell us about some of those other takeaways and conclusions? You just mentioned quality of life; disability is more. What else did we learn, some of the things you didn’t highlight already? 

Lipton: For people living with migraine, the point I want to emphasize is this. First of all, there is a belief that the presence of neck pain is not just an incremental burden of migraine, but it’s also an opportunity. And so many clinicians believe – and this is not incredibly well studied in specifically designed randomized trials – but many clinicians believe that onabotulinumtoxinA may be a particularly appropriate preventive treatment for people who have chronic migraine with neck pain. And, of course, chronic migraine is primarily defined by migraine on 15 or more headache days per month. 

And we don’t know that onabotulinumtoxinA works in episodic migraine, the evidence on that issue is not in yet. But we know it works in chronic migraine. And many clinicians, including myself, are more likely to treat people with neck pain and chronic migraine with Botox.

And then, of course, the other thing is if you keep a diary and notice that on a regular basis you get neck pain before your headache begins, and that most of the time neck pain heralds an impending headache, then that creates an opportunity to use ubrogepant to treat during the prodrome before headache begins. 

Now, my expectation would be that maybe other drugs in that same class of gepants would work, but that has not been studied. Gepants like ubrogepant work by binding CGRP receptors. The receptors are there all the time; the target is there, so you would predict they might work during prodrome. And, in fact, that was the prediction that led to the PRODROME study. 

But really, having evidence that you can treat before a headache begins really is a whole new paradigm of acute treatment, but it’s part of a trend in the following way. Early in the triptan era, we said what’s great about triptans is you can treat anytime during the attack, they work for moderate or severe pain, and all our studies were of people who were instructed to wait until their pain was moderate or severe before they treated. 

Then we discovered that basically all classes of acute treatment work best if you treat early in the attack while pain is still mild. And that’s true for triptans, and it’s true for gepants. And it’s true for aspirin and metoclopramide, and it’s true for nonsteroidal anti-inflammatories. And treating during the prodrome is the next step in that trend of treating earlier and earlier, but if you’re going to treat during the prodrome you have to select the drug that’s correct for that target. 

And then the final step which is still emerging is what I call situational prevention. So when you treat during the prodrome, the patient is symptomatic; they have neck pain, or cognitive disturbance, or sensitivity to light, or sensitivity to sound, or some feature or combination of features that lets them know a headache is coming. But they’re symptomatic. The still next step in the trend towards earlier treatment again is situational prevention where you treat not because you have symptoms, but because you’re in a situation where the probability of headache over the next little while is very likely. 

And examples of that might be… well, it’s Ramadan this month, so if you’re fasting during Ramadan, fasting may trigger a headache. If you’re a woman who has headaches associated with your menstrual cycle, you may know a headache is coming because it’s just that time of the month. If you always get headaches when you travel, you could treat it in anticipation of boarding the airplane. If you always wake up with Saturday morning headaches either because you drank on Friday night or because you slept through your cup of coffee, or because you’re relaxing after a stressful week, that’s an opportunity for situational prevention. 

And that’s become an area of very active study now. But it’s all a trend towards earlier and earlier treatment with an eye towards preventing headache. And the reason that’s so important is that if you take a triptan or a gepant after your pain develops, you may wait a couple hours or sometimes longer for the treatment effects to kick in. And that may mean you can’t go to work. Or you’re deciding should I go to work or not; I’ve got this terrible headache, maybe I feel too sick to drive. So the possibility of completely preventing headache with medications you take only when you need them really is incredibly attractive to a lot of people if they hear about it. 

O’Brien: I don’t know why I’m so blown away with that. I think it’s just so exciting that we now have the research and knowledge to back it up, and there’s more on the way. But it make so much sense now that we know more about the anatomy and how migraine works and the mechanism. So to know, okay, this seems to work, it seems to stop it before it comes and taking it earlier and earlier. It just all makes so much sense and it’s fascinating. So I appreciate all your insight on that. 

Do we know if any other treatments seem to be effective for people who have neck pain associated with migraine, like trigger point injections, like occipital nerve blocks, or nerve blocks in general? Do we know if any of those seem to be effective?

Lipton: We use a lot of other treatments with, honestly, variable amounts of evidence. So if somebody has neck pain and a lot of trigger points, we’ll inject their trigger points. If somebody has neck pain or pain at the back of the head, and I can press on their occipital nerve and replicate their headache pain, we certainly do occipital nerve blocks. The rigorous evidence that trigger point injections and occipital nerve blocks work is not strong, but the anecdotal evidence is very strong. And at the end of the day, as a scientist I want to use only proven therapies, as a clinician I want to make my patient’s life better today or tomorrow. And so we do a lot of things that are safe, waiting for the compelling double-blind evidence that they work. 

I should also say that when headaches occur in the setting of traumatic brain injury, there’s a disorder of headaches that begin in close proximity to a head injury that are simply called post-traumatic headache. Those headaches often remit on their own after a few months. But particularly in people with antecedent migraine, or in people with a family history of migraine, those headaches may persist, and neck pain may be part of it. And in that context, the flexion-extension injury of the neck may be part of the cause. In those settings, sometimes a cervical collar can be helpful on a short-term basis, but you don’t want to use it so much that the neck muscles weaken and atrophy. 

So those are all options. And something emerging that’s very interesting are the use of devices. So sometimes stimulating the supraorbital nerves with a device called Cefaly can actually help with neck pain, because you stimulate at the front, but it blocks the input from the back. There are devices that stimulate the occipital nerves, and that can be helpful in people with posterior pain. And these are all external devices, you stick them on or apply them when you need them. But there are a couple of implantable devices that are currently in clinical trials which may become an important option for people whose headaches are refractory to the other usually effective alternatives. 

O’Brien: Amazing. Dr. Lipton, it’s been such a pleasure speaking with you today. And such incredible insight and knowledge, we really appreciate you sharing it with our audience.

Lipton: My pleasure. Thank you so much for inviting me. 

O’Brien: It’s been a fun chat; we really do appreciate your time. And to all of our followers out there, thank you for listening. This podcast is made possible by supporters like you. If you enjoy our content and would like to hear more, make a tax deductible donation today at migrainedisorders.org. That’s Spotlight on Migraine. I’m Molly O’Brien. We’ll see you next time.

---

*The contents of this podcast are intended for general informational purposes only and does not constitute professional medical advice, diagnosis, or treatment. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical condition. AMD and the speaker do not recommend or endorse any specific course of treatment, products, procedures, opinions, or other information that may be mentioned. Reliance on any information provided by this content is solely at your own risk.