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Voice-over: Welcome to Spotlight in Migraine hosted by the Association of Migraine Disorders. Join us for fresh perspectives by medical experts and advocates as we explore the spectrum of migraine and dig deeper into this complex disease. Thank you to our 2023 education sponsors. What is allodynia, and why does it happen? In this episode, Dr. Gretchen Tietjen answers these questions and more, diving into the nuances of this symptom that is often associated with migraine.

Gretchen Tietjen, MD: Okay, thank you. All right. I have nothing to disclose as it pertains to this presentation. So, one of the things that I want you to get out of it, by the time we’re done with this presentation, one is what exactly is allodynia. And I always like to say the answers before I actually go over it, but it’s pain. It’s a special kind of pain, but it’s pain. So why does it happen? We’ll discuss that. How’s it associated with migraine ,and is it associated with other conditions, and what’s the risk if you have migraine, which probably many of you do here, what are the risk factors for developing allodynia? And are there complications of having allodynia, and how is it diagnosed, and is there a treatment for it?

So allodynia, simply, it’s an experience of pain, but it’s from a stimulus that doesn’t normally cause pain, and we’ll go over sort of what type of stimuli those are. In some people, that allodynia like is restricted to the head. If they touch their hair or brush their hair or take a shower, that causes pain, even though that’s a nonpainful stimulus. Sometimes, though, people can have allodynia over any part of their body. You know, they touch a few drops of cold water on their arm, and it’s very painful. I know the first time I saw allodynia I knew the patient well enough to know she didn’t fake things. But I’ll tell you, I went to examine her, and she’d gotten much worse in her migraine from the time before I had seen her, and I just touched very lightly over the shoulders. I was going to press and I hadn’t even started yet, and she just recoiled in horrible pain and started crying and said I was hurting her. And I was shocked. I thought what in the world causes that kind of experience?

So, as I mentioned, things like brushing hair, washing one’s face, taking a shower, putting the head on the pillow. You can imagine if you have to sleep, that would be difficult, tight clothing, pulling the sheets up, exposure to hot or cold temperatures on the skin. Now, what is it not? And, you know, I always previously thought of it as this sort of they’re super sensitive to pain. It’s not that exactly. It’s more like it’s a dysregulation of how they process the pain signals. And I’ll show you a picture that I think really helps explain that, because it’s not pain that they’re feeling. So it’s not a painful stimulus and they’re just sensitive to that painful stimulus. It’s not an increased response to pain because they’re not given a painful stimulus. And it’s not the result of physical damage. If you were actually able to biopsy a body part that had a lot of pain sensitivity, like over the trapezius or something, there’s nothing that looks wrong with it.

Now, it’s put in a category of two different phenomenon, and they’re called neuropathic pain. And one is allodynia, which is the topic of this. The other is hyperalgesia, and they sort of tend to go together. So what’s hyperalgesia? It’s when you have an exaggerated response to something that is normally painful. So you’ve experienced, let’s say, menstrual cramps in the past and you have them, but it’s like it hurts much, much, much worse. Or somebody gives you a slight little punch on the arm and normally that makes you feel a little sore, but this was excruciating. So it’s a heightened pain response. Now allodynia, as I mentioned, was a type of pain due to a stimulus that does not normally cause pain. And so, as I said, it seems like it’s an abnormal processing disorder of that nonpainful stimulus.

So there’s three types of allodynia that I’ve alluded to in the examples that I’ve given you. When I talked about touch, that’s also called tactile allodynia. So, you know, you get a little tap on the shoulder and that hurts or, as with my patient, I touched over a muscle, just laid my hands on her neck and that was very painful. There’s mechanical allodynia and that’s oftentimes movement related. So, brush your hair, pull up sheets over your body, that type of thing. And then there’s thermal allodynia and those are the ones with temperature-related changes, even very mild, that can cause pain.

So why does it happen? Well, as I mentioned, it seems like it’s a pain processing dysfunction in the central and also can be in the peripheral nervous system, but we oftentimes refer to something called central sensitization, and you might have heard that term before, especially if you have a number of different pain disorders that seem to be tied together possibly through this mechanism. And that’s an amplification of nerve pain signaling. It can be due to things like you could get it because there was some damage to a peripheral nerve certainly, but it’s a dysregulation of brain chemicals. And one of those neurotransmitters, it could be substance P/glutamate, that they’re increased and those cause some of the problems with how the brain is processing what they’re experiencing. And there also could be inflammation. It could be due to abnormal stress responses and autonomic nervous system things. It can have a lot of different causes of them. And also it could be related to some difference in brain structure and function.

Now, I wanted to just show this picture because I think it helps explain it. You have two parallel systems of sensory nerves, one is if you get a high intensity stimulus, and those are the nociceptors. And so this is an afferent, it’s carrying it into the nervous system, and you experience a painful stimulus through your nociceptors carrying that signal, and then you experience pain. That’s what normally happens. But the parallel tract – and there’s not much interaction between these tracts in a normal person – is where you get a low intensity signal, so touch, and it stimulates the low threshold mechanoreceptors, and then you experience it as touch.

Now, this one’s a little bright, so I hope I don’t set off anybody’s migraine. But anyway. So what happens when it’s abnormal? You get that high intensity stimulus, but you don’t just feel pain, you feel super pain, you feel hyperalgesia. And algesia’s just a word for the pain symptom that you have. Then a low intensity signal, what happens is this parallel tract that normally doesn’t interconnect you can see…let me see if I can point to where I’m talking about right here. Normally those two run and it just goes to touch. But with central sensitization, that connection suddenly becomes important because it now connects you to this nociceptive pain system, and you get allodynia, which is the pain.

Okay. So what are some disorders? Well, some of the things that I referred to as central sensitization disorders are things like postherpetic neuralgia. It’s a type of pain you would get after shingles. So the shingles have healed, but you still have sensitivity in that, and that’s mostly from maybe some peripheral nerve damage. Diabetes, complex regional pain syndrome, also formally called reflex sympathetic dystrophy. But what we’re going to talk about today is migraine and some of the painful syndromes that can be seen in persons with migraine at a higher level than normal. And these can be things like fibromyalgia (I’m not going to read all those for you) but irritable bowel, osteoarthritis, TMJ, chronic fatigue.

And a number of years ago, a group of headache clinics in the US and Canada, we got together about 1,400 patients, I think, in this. And so they all had migraine because it was a migraine clinic, but we divided those into those that had symptoms of allodynia and those that did not. And what we found is those that had allodynic symptoms, like when you brush your hair does it hurt, that kind of thing, they were more likely to have these other central sensitivity syndromes like IBS, fibromyalgia, chronic fatigue, depression. But what we also found (and it’s a little hard to see here) but what you have there on the Y axis is how many allodynic symptoms did they have and we said oh you only have one, oh you have two, you have three, you have four or more. And when we stratified it by how many symptoms they had, we noticed a big difference in the number of pain syndromes they also had. So if somebody, for instance, had only one symptom, 13% of that population had two or more pain syndromes, like fibromyalgia or irritable bowel. But if they had four or more, it was 46% that had two or more pain syndromes. So the number of other pain syndromes rose with the number of allodynic symptoms they correlated.

So, they think that up to 70, even 80%, of people that have migraine, at some time, experience allodynia. A lot of times it may be just during the attack initially if you take a medication, and it doesn’t work or you don’t have any medication, you don’t treat it. But 10 to 20% of people that have allodynia have it, and it’s very severe for them. So what are some of the risk factors? One would be developing…well, if you had high frequency, high intensity of attacks if all of a sudden your attacks are getting worse, you’re more likely to get allodynia. And I would mention that if you develop allodynia, that doesn’t go away with an attack, that’s a sign that your migraines may be worsening and getting more severe.

Migraine with aura. In some studies and the one we did was associated with allodynia. Premenopausal status, so where you have female reproductive hormones like estrogen in the system that fluctuate. Obesity. You know, we know there’s a lot about fat that has inflammatory factors related to it. Maybe that has some role. Smoking, if a person’s a cigarette smoker. And then one thing that I’ve done research on is history of adverse childhood experiences, things like abuse or neglect, but it also could be just parent dying, separated, being sick and in the hospital for a while. A lot of stressful things could predispose a person to migraine. There’s been a lot of studies on association, but also predispose them to having allodynia with migraine.

So what are some of the complications? Well, you can imagine if you can’t even rest your head on a pillow and get sleep at night, you’re going to develop sleep disturbances, fatigue that might go along with that, depression, and anxiety. And anxiety is something that sort of always amplifies pain, so you can kind of see this as a vicious cycle. And how do you diagnose it? Like if you’re wondering do I have allodynia? Over the years since the time I first did my research on it there’s been some really nice checklists that are much more thorough and have been validated in a way for a clinical disorder, but it’s a clinical diagnosis based on the history and examination, a lot of it from questions. And there are some nerve sensitivity tests, like EMG, nerve conduction studies, but those are usually to rule out other causes. There is not a test that you can do objectively to find that yes, this is allodynia.

Now this is something that you can find that’s called a 12-item allodynia symptom checklist, and I’m not going to read all those off, but they’re a lot of the ones I’ve mentioned. Some of them are things like wearing earrings, wearing a necklace, wearing tight clothing, contact lenses, eyeglasses, shaving your face, you know, these type of things. And then do you get it never, rarely, you don’t get any points for that, but if it’s less than 50%, but more than rarely or more than 50% of the time. And then you sort of sum up all your things and it sort of stratifies you as to whether it’s mild, moderate, or severe. And some of them you get two points for it if it’s more than 50% of the time that you’re getting some of those symptoms.

So is there a treatment? Well, the treatment is just really to treat the underlying condition. If migraine, for instance, maybe starting or adjusting preventive medication or other strategies that you’re using. If you’re taking an acute medication, let’s say it’s a triptan, you want to take it sort of, if you can, before the headache starts to throb because that’s sort of the sign of peripheral sensitization and it may tell you that you’re leading into allodynia. Gabapentin and pregabalin are medications that have been used to treat nerve pain. Sometimes they are used in people that have this, it may make it a little better. Tricyclic antidepressants are the same thing. They’ve been used in things like migraine, fibromyalgia, irritable bowel even, and, you know, maybe they have some effect on the allodynia, but they’re also treating the underlying condition, at least as far as pain.

Topical medications have been tried. Nonsteroidal. And then there’s some literature on people that have lessened their allodynia and maybe treated the underlying condition with this, but when they try to alter their pain responses through cognitive behavioral therapy, mindfulness, that type of thing. Acupuncture’s also been studied, as has the role of exercise. But none of these are really full proof and they’re not necessarily just treating the allodynia. They’re sort of involved in the whole treatment of the underlying condition.

So, to just summarize, it’s pain that’s caused by nonpainful stimulus. As I said at the beginning, it’s a pain processing problem. In people that have allodynia, I mean it’s very common in migraine and related pain conditions, as a number of the one’s I’ve mentioned and had on the slides, that its risk factors are severe migraine. So, if you have severe migraine, you’re probably going to get worsening. And other things like aura, female sex, smoking, obesity, those things that I had mentioned, early life stress. And it can cause the sleep problems, fatigue, depression, anxiety. The diagnosis is based on the clinical symptoms, and you can find that 12-item checklist. And then, treating things, nothing specific for it, but that list of things I had on the prior slide are all things that have been done and sometimes can definitely help the migraine and that usually helps the allodynia. And it’s nothing that I found, as a physician, more rewarding than to treat somebody and have that symptom go away because that was very bothersome and disabling in some cases. All right. Thank you very much.

Voice-over: Thank you for tuning into Spotlight on Migraine. For more information on migraine disease, please visit MigraineDisorders.org.

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