In part 1 we explained the underlying cause of menstrual migraine, as it is with other chronic headache and migraine types, is an overactive part of the brainstem called the trigemino-cervical nucleus or TCN. At the heart of this over activity is the interconnection in the TCN between the nerves from the upper part of the neck, and the nerves thatsupply the head and face. Hormones simply make it easier for this overactive brainstem to cause migraines. Let me explain further.
Oestrogen plays a critical role in the production of serotonin and also helps the brainstem to absorb serotonin. When oestrogen levels drop around day 1 of the menstrual cycle the levels of serotonin drop as well.
Changes in the level of serotonin have a significant impact on headache and migraine. In fact the medications from the triptan family (e.g. Imigran, Naramig, Maxalt, Relpax, Sandomigran) are effective because they make the brainstem absorb more serotonin.
So what does serotonin do?
Increasing the levels of serotonin decreases activity in the brainstem, and stops activity “spreading” to the extent where it “switches on” the nerves of the head and face causing pain – a headache or migraine. It’s not just having more serotonin though. Too much as well as not enough will cause problems because serotonin also impacts on the blood vessels on the lining of the brain.
A decrease in Serotonin will cause these blood vessels to dilate, contributing further “information” to an already overactive brainstem. Added to the loss of control of this over activity and it is not hard to see why the nerves in the head are “lit up” causing a migraine.
Around mid cycle when oestrogen levels rise, serotonin levels rise causing blood vessels to constrict. This mechanical input from constricting vessels is enough in some people to trigger another headache, similar to the day 1 migraine, but commonly far less intense and often not migrainous in nature.
The fluctuation in oestrogen and hence, serotonin is no different in menstrual migraine sufferers and non-sufferers. This has prompted leading expert in menstrual migraine Elizabeth Loder to say:
“We must look at other factors (other than hormones)…………. Abnormal central nervous system response to normal fluctuations in hormones is the likely underlying cause of menstrual migraine”. (2001)
Menstrual migraine is treatable, not by trying to treat hormones, but trying to treat the underlying activity in the brainstem. The upper cervical spine has the most significant input into the brainstem and in 80% of cases the usual pain of migraine and headache is able to be “switched on” by selective and specific pressure applied to the upper part of the neck. If this reproduced pain eases as we sustain the pressure, then treatment will be successful in 90% of cases.
Did Elvis die with a migraine?
In the 1960's and 1970's severe headache and migraine were not well understood (some might say little has changed). Due to many of the now familiar traits we associate with migraine, many behaviours were often mis interpreted as drug related, and those seeking assistance often mistaken to be abusers of illicit drugs and often, sadly, turned away from hospitals. In fact a stigma was often attached to the disorder as it was thought to be psychosomatic by the medical profession.
In 1973 Elvis was admitted to hospital on numerous occasions for treatment of headaches and high blood pressure. In 1975 he underwent an "extensive eye examination" later discovered to be for migraine aura. Some of his other symptoms were sensitivity to light, sound, pain, slurred speech, and fatigue.
Leaked information from Elvis' autopsy revealed a number of medications in his system at the time of his death.
Demerol, Propranolol, LSD and antiemetics.
Demerol (narcotic pain relief), propranolol (beta blocker - blood pressure) and antiemetics (stop vomitting) were all fairly standard drugs prescribed at the time for intractable migraine.
The only other abortive prescription drug for migraines at the time was an ergotamine - DHE45 which is related to LSD structurally, and often tested positive as LSD.
Far from partying on hallucinogenic drugs at the time of his death, Elvis may well have been in the midst of yet another migraine attack.
Little is known about when they started as due to the stigma attached to the condition, it wasn't reported, but it is amazing to think he achieved what he did whilst carrying around the burden of migraines, especially with the medical regime available at the time.
"Abnormal central nervous system response to normal fluctuations in hormones is the likely cause of menstrual migraine. Patients with menstrual migraine do not generally have hormonal abnormalities."
Elizabeth Loder MD
Menstrual Migraine - Opinion Statement
Current Treatment Options in Neurology, 2001, Vol 3 (2)
Where is this abnormal CNS response? In the brainstem, where the upper cervical nerves mix with the trigeminal nerves.
The ability of the upper cervical spine to contribute significantly to the underlying abnormal CNS activity has been majorly underestimated, largely because traditional manual techniques have been ineffective for treating headache and migraine.
Now using techniques developed specifically for headache
Often referred to as hormonal migraine or hormonal headache it might at first seem unusual that this could be related to the neck.
Clearly it is hormonal. The timing of it dictates that there must be a direct link to the hormones, and there is.
However, as Dr Elizabeth Loder (2001) noted, “Patients with menstrual migraine do not generally have hormonal abnormalities.”
So what is happening?
Put simply the underlying problem is an overactive brainstem. The drop in oestrogen affects this underlying activity making it uncontrollable, and the result is severe headpain. The upper cervical spine is in the box seat to cause or at least significantly contribute to this over activity.
In the remainder of part 1 I will expand on the role of the brainstem and the evidence for it’s over activity in menstrual migraine. Part 2 will look more at the interaction between the brainstem and hormones, particularly oestrogen.
A small area in the brainstem of chronic headache and migraine sufferers is overactive. This is also true for menstrual migraine sufferers. This small area is called the trigemino-cervical nucleus or TCN. The TCN receives all the input (other than special senses – sight, smell, hearing, taste) from the head and face and also receives information from the upper three cervical nerves. So any information, from a scratch on the head, to the sensation of muscles in the scalp contracting, and even the pulsing of blood vessels on the lining of the brain all send their information back to the TCN where it must be relayed onto central nerves to be sent to the brain. Once this information arrives at the brain you become aware of whatever the sensation is.
If this area is overactive it means that your brain can receive information, for example “throbbing” from the blood vessels on the lining of the brain, without the nerves on those blood vessels being active. In effect your brain feels something that really isn’t there. This is called referred pain. The same is true for a vast majority of headaches. There isn’t a problem where you actually feel the pain, but it is referred from somewhere else. That somewhere else is the TCN.
Inside the TCN we have all the nerves arriving from the face and head, and they intermingle and interconnect with the upper three cervical nerves and this area is overactive. How do we know?
Two important studies confirm that the same process that is occurring in other chroninc headache and migraine types, is also occurring in Menstrual Migraine.
In 2005 Mannix and Files published a study regarding the use of triptans in menstrual migraine. Triptans are a drug that “turn down” the activity of the TCN, and by doing so turn down or switch off headaches and migraines by stopping the referral process. For these to be effective in menstrual migraine there must be over activity in the TCN.
In 2009 Varlibas and Erdemoglu studied a reflex that goes through the TCN. Reflex activity, whether they are dulled, normal or excited inform doctors and researchers about how active the central nervous system is. They found that menstrual migraine sufferers had “excited reflexes” compared to non-migraine controls, during their attack and outside of an attack. This supports research in non-menstrual migraine, Tension Type Headache, cervicogenic headache and cluster headache, indicating the TCN is always over active, and not just during a migraine attack.
These studies confirm that the underlying process in menstrual migraine IS an overactive TCN. So where is this overactivity coming from?
In a vast majority (over 80%) of cases it is a problem in the upper cervical spine that is causing constant input into the TCN and making it overactive. Using dedicated “headache specific” techniques this problem is assessable, treatable and self manageable in most people.
So how do the hormones relate then?
In Menstrual Migraine part 2 we will look at the role of oestrogen and its effect on this over activity.
To recap on the anatomy of the TCN, and the role of the trigemino-cervical nucleus in headache and migraine you may wish to read some earlier posts on this blog.
Loder, E (2001) Menstural Migraine. Current Treatment Options in Neurology, Vol 3 (2), pp 189-200.
Mannix and Files (2005) The use of triptans in the management of menstrual migraine. CNS Drugs 19 (11), pp 951-972.
Varlibas and Erdemoglu (2009) Altered trigeminal system excitability in menstrual migraine patients. Journal of Headache Pain, 10 (4), pp 277-282.
Both migraine and depression are significantly more common in women than men. Oestrogen plays a significant role in the production of, and the bodies ability to use serotonin.
Serotonin is thought to be a key player in both headache (including migraine) and depression due to the action of drugs that help boost serotonin in both conditions.
In migraine and other headache types, serotonin makes it harder for nerves from the upper cervical spine to "set off" the nerves in the trigeminal system which would give you head pain. In effect serotonin acts as a fire break, stopping the spread of the "fire" or activity in the brainstem.
Serotonin is also critical in other bodily functions and mood regulation - a depressed mood is thought to be related to abnormal serotonin levels - initially thought to be low, however this is hard to measure and there may be some suggestion for some people their serotonin might actually be high.
"Oestrogen makes both of these worse," he (Dr J Saper - Michigan Headache Institute) said describing the headaches and mood changes often triggered by the menstrual cycle. "Women are more prone to depression and more prone to migraines, and women who take oral contraceptives are often worse off."
The problem is that we can't measure serotonin in the brain of live humans so it is difficult to prove other than by association. Blood levels of serotonin can be measured and are low in people with depression, but it is not known if this is also true for the brain.
Roger O'Toole is the Director and Senior Clinician of the Melbourne Headache Clinic and has over 10 years experience as a physiotherapist.