Today in Neurobiology the topic of migraines and headaches was brought up. There was a question raised that wasn’t able to be answered adequately, and that question was, “Why do we experience the sensation of pain inside our skulls during a headache despite the fact that there are no nerves there?” Is there any primary research on this subject?


  1. Rieux says

    Is there a setting you can change so that the text of this post shows up in the same font and font size as the other posts on Pharyngula? (Or is it only on my Windoze/Internet Explorer configuration that this one looks out of sync?)

  2. Barn Owl says

    I have one word for you: meninges.

    a. inside the skull
    b. innervated (afferents via meningeal branches of the trigeminal, vagus, and first two cervical nerves)

    Meningeal innervation accounts for the headache and reflex nuchal (neck) stiffness associated with meningitis.

  3. CJO says

    The phantom limb phenomenon has been studied. Similar perhaps? Of course, in that case, there not only are no neurons, there’s no nuthin’. So clearly, nerves need not exist at a particular location in order for us to have sensation there.
    Here’s a list of articles on phantom pain from Google Scholar

  4. Christian Burnham says

    It’s an evolutionary defense mechanism.

    Migraine pain is nature’s way of telling us that we should perform trepanation on our skulls so that we can do elementary self-brain surgery to get to the root of the problem.

  5. David Marjanović says

    (Or is it only on my Windoze/Internet Explorer configuration that this one looks out of sync?)

    Nope, Safari and Mac OS X here.

  6. David Marjanović says

    (Or is it only on my Windoze/Internet Explorer configuration that this one looks out of sync?)

    Nope, Safari and Mac OS X here.

  7. Bob L says

    The pressure on the outside of the scull from the brain parasite larva that have just hatched.

    Who says biology can’t be fun?

  8. Barn Owl says

    harderkid has a legitimate neurobiology question. Why not help him or her out, rather than invoking phantom limb pain or sky fairies?

    harderkid- Try entering “migraine” and “meninges” as search terms in PubMed. That gave me numerous hits when I tried it just now. Here’s a relevant sentence from a 2007 abstract by Zhang XC et al. (in J. Pharmacol. Exp. Ther.):

    Intracranial headaches such as migraine are thought to result from activation of sensory trigeminal pain neurons that supply intracranial blood vessels and the meninges, also known as meningeal nociceptors.

  9. Mike says

    From Wikipedia:

    Migraine was once thought to be initiated by problems with blood vessels. This theory is now largely discredited. Current thinking is that a phenomenon known as cortical spreading depression is responsible for the disorder. In cortical spreading depression, neurological activity is depressed over an area of the cortex of the brain. This situation results in the release of inflammatory mediators leading to irritation of cranial nerve roots, most particularly the trigeminal nerve, which conveys the sensory information for the face and much of the head.

    This view is supported by neuroimaging techniques, which appear to show that migraine is primarily a disorder of the brain (neurological), not of the blood vessels (vascular). A spreading depolarization (electrical change) may begin 24 hours before the attack, with onset of the headache occurring around the time when the largest area of the brain is depolarized. The effects of migraine may persist for some days after the main headache has ended. Many sufferers report a sore feeling in the area where the migraine was, and some report impaired thinking for a few days after the headache has passed.

  10. says

    Rieux, I think harderkid13 is the one who’s chosen a different font from the standard Pharyngula settings. If you think it’s too small you could always change the settings on your own browser to increase the size (holding ctrl and using the scroll wheel, if you have one, should do it).

    Oh and change to Firefox! :P

  11. says

    Felicia, looks like he’s hard-coded the font, probably by copy-pasting from a word processing program (for future reference, don’t do that–it messes with your HTML). The scroll wheel won’t do the trick.

    On topic: what Barn Owl said. Try PubMed–if you are a student, I would guess you could get access via your library’s database links.

  12. Big Dave says

    Meninges quite correctly cause headaches – for example the dehydration from a hangover can be felt very accutely there (though not by sickening people like me. Any way, I digress).

    As for phantom limbs, I can remember watching something on (I think) the BBC ages ago. Am sure Susan Greenfield was involved in it some how.

    One of the treatments shown used mirrors. A person was placed in front of a box. The mirrors were set up, so that their one arm was reflected, and appeared in their vision to be where their old arm used to be, this helped releive the symptoms.

    I’m afraid I forget when I saw this. It may well have been the BBC’s Horizon series, Equinox on Channel 4 is another possibility. These are both British channels.

    Hope that helps as a basis for a search.

    Either way, good question!

  13. mothworm says

    I have terrible migraines, and never had any success with migraine medicine until a new doctor gave me Relpax, which, if I remember correctly, is actually an anti-seizure drug. I forget how this was supposed to work, but I do remember him saying that the old model was that blood vessels swelled and pressed on a nerve (or something), causing pain, whereas they were now thinking of migraine as something akin to epilepsy.

  14. LM says

    I have heard something similar, mothworm. I have epilepsy and the only times I’ve ever had migraines were either immediately preceding or immediately after a tonic clonic seizure. Of course, not everyone with a seizure disorder experiences migraines, and not everyone with migraines has seizures. The brain is a funny, funny thing.

  15. says

    So to oversimplify, it’s your skull, not your brain, that hurts. For example, maybe the blood vessels in your brain are swollen and it gets a little cramped in there.

    #10 (at #2):

    Firefox for Windows works fine.

    Odd – everyone else in every other platform and browser (including me: Ubuntu/Firefox) sees the body text formatted differently from PZ’s usual style. I’d be tempted to go with majority rule and assume the kid did something wrong, but I looked closer for proof. Usually, PZ has

    tags around his paragraphs. The kid doesn’t. So at least that rules out a browser issue.

    #12 (at #2):

    Oh and change to Firefox!

    While you’re at it, make sure to upgrade to Ubuntu!

  16. Xerxes1729 says

    I’m pretty sure that the cell bodies of the afferent (sensory) neurons are in the dorsal root ganglia. Amputation of a limb would sever one of their axons, but they would still be able to send signals to the brain.

  17. Don Quijote says

    @Big Dave
    There was an article in The Economist not long ago, describing the mirror treatment. I do not know much about the topic but I would guess that it is not what harderkid13 is looking for.

    P.S.: I found the article. It was longer ago than I thought: “Phantom Limbs and Chronic Pain – A Hall of Mirrors” (The Economist, 20 July 2006). Sometimes I feel like Rip Van Winkle :/

  18. mothworm says


    Yeah, I haven’t got epilepsy (unless that’s something to look forward to). For a long time, I couldn’t get a doctor to treat my headaches as migraines because they weren’t hemispherical, and I didn’t have any scintillating scotoma (oddly, I have recently developed those, but they come and go independently of migraines). They kept calling them “tension headaches”, and nothing they prescribed worked. My current doctor says the medical thinking, now, is to treat any severe headache as if it were a migraine (which he did, and thankfully, that solved the problem).

  19. says

    Mothworm — A few years ago I worked on migraine drug marketing. Relpax is the tradename for eletriptan, which was Pfizer’s answer to sumatriptan (Imitrex), the first migraine drug designed to affect a subclass of serotonin receptor supposedly linked to vascular inflammation in the brain. There are other serotonin receptors linked to depression, etc, but they’re different I think.

    The thing is, the triptans were designed to work on the blood vessels, based on the “vascular theory” outlined by Mike above. Which by the time Relpax was getting ready to launch, was already out of favor… yet these drugs do work pretty well, apparently! So much for rational drug design.

    Mercifully, I don’t get migraines although my wife manages hers with ibuprofen and caffeine. But anyone who has trouble managing them, get a specialist opinion, because there are a lot of treatment options.

  20. says

    If you want a little history on migraines, I actually write about it at some length in Soul Made Flesh. Migraines were quite a mystery in the 1600s. The main subject of my book, Thomas Willis, treated the migraines of a philosopher named Anne Conway, for whom the migraines became an inspiration for her philosophy.

  21. OhioBrian says

    Here’s a curve ball: in times of extreme stress, I get the scintillating scotoma, but there is no corresponding headache. My optometrist listened to me describe the visual phenomenon I was seeing, and he told me it was a classic description of the visual aspects of a migraine. Very luckily for me, while I’ve had to watch the pretty lights about a dozen times in the past five years, I have yet to have an actual headache — the worst I’ve had has been a slightly stiff neck.

  22. says

    nothing like being chided for goofing off in a blog comments thread. makes the day seem, well, a little brighter.

  23. Siamang says

    “Why do we experience the sensation of pain inside our skulls during a headache despite the fact that there are no nerves there?”

    That’s a trick question, right?

    What’s yer brain made out of, spongecake?

  24. AnInGe says

    Re: BigDave’s post # 14:

    I suspect the BBC program you mention concerns the work of psychologist and neurophysiologist Vilayanur S. Ramachandran. He has written extensively on his research and cures for phantom limbs. Google on his name to find a lot of this info.

  25. divalent says

    Basically, where you think the pain is located does not necessarily correspond to where the injury/lesion/inflammation is. It really just our imagination that locates things.

    For surface pain/touch receptors (as opposed to interior pain sensors), we can 1) learn through experience (see mosquito there, must be location of pain), and (WARNING! ADAPTATIONIST SPECULATION COMING UP!) 2) we may be wired innately to more precisely pinpoint the location because we can do something about it (you can scratch your elbow, but not your hippocampus; so it is helpful to be able to pinpoint surface pain sites, but knowing exactly where that mosquito is sucking juices in your brain does you little good beyond knowing that he’s somewhere in there).

  26. Big Dave says

    Thanks for the responses guys!

    Sorry it’s not going to help much with your original post harderkid13.

    That said, if you want any information on meningitis (which has been mentioned a bit), I work for the Meningitis Trust, the leading meningitis charity in the UK, one of our main aims is raising awareness and educating people about the disease, so you’re welcome to get in touch if it becomes relevant at some point.

    Check out more at http://www.meningitis-trust.org

    /shameless plug

  27. says

    I get migraines (Imitrex works wonders), and a bad migraine was the worst pain I’d ever experienced. And then this one time, I got meningitis. OMFG. Whoever invented hydromorphone — well done!

    I can’t say anything about the mechanism, but headaches can be debilitating.

  28. CRM-114 says

    I get acephalgic (no-pain) migraines with bilateral scintillating scotoma. Bad attacks bring the blue-yellow zigzagging which leaves behind a bilateral central blindspot spreading over most of my visual field, blinding me for half an hour to an hour. I also get paresthesia (tingling) in my left leg and sometimes left arm, but never in conjunction with the scotomae.

    My first attack came when I was the only one manning a station at a remote site in the desert, and it scared the hell out of me.

    I am disturbed by how many doctors fail to recognize the symptoms. They act like they think you’re making it up. I found out it was migraine thanks to a column in The Smithsonian.

  29. says

    My understanding (as a chronic migraine sufferer) is that a migraine is an electrical storm in the brain, not unlike an epileptic seizure. So the pain isn’t real in the sense that it’s not the result of an injury, infection or other inflammatory source, which makes it all the more maddening.

    Pain without a reason, especially pain that’s inside your head, is enough to drive you fucking nuts. More than once I’ve fantasized about driving an icepick through my eye, just because it seemed like controlling the awful pain would be better than being its victim.

    I wish they could do the same kind of corpus callosum split for chronic migraine sufferers that they do for severe epileptics – I wouldn’t mind relearning left-right coordination if it meant freedom from 10-14 migraine days a month.

  30. Cappy says

    So, were any of you migraine sufferers ever hit in the head when you were children. I lived with a woman some years back who suffered terrible migraines. I did a little reading and learned that, beyond genetics, some sufferers had experienced childhood head injuries (my girlfriends case: her brother and a baseball bat). One book had a regemine of massage to the head and face, especially concentrating on the area of the injury (hurt like hell for a while but then the pain went away). This was back when the circulatory theory was prevalent and the explanation was couched in those terms. It really seemed to work, though.

    As to why you feel it in your head when there are no pain receptors there: like the phantom pain, all pain is perceived in the brain no matter where the signal comes from or whether it generates the signal itself.

  31. David Marjanović says

    That’s a trick question, right?

    What’s yer brain made out of, spongecake?

    It doesn’t contain any pain-sensitive nerve endings. If stimulating any nerve cell anywhere would always lead to pain, it wouldn’t be stupidity that hurt…

    BTW, the font has turned to normal — and I’m at home, where I have IE7 on Windows XP.

  32. David Marjanović says

    That’s a trick question, right?

    What’s yer brain made out of, spongecake?

    It doesn’t contain any pain-sensitive nerve endings. If stimulating any nerve cell anywhere would always lead to pain, it wouldn’t be stupidity that hurt…

    BTW, the font has turned to normal — and I’m at home, where I have IE7 on Windows XP.

  33. Cappy says

    Also with my old girlfriend, she would often get the “post stress” migraines. She would be under a deadline with lots of stress and be fine. As soon as the project was complete and the stress was gone WHAM! she’d be holed up in the dark with a terrible headache. Red wine and other complex organic foods (chocolate, mushrooms) sometimes did it too.

  34. Barn Owl says

    My woo-meter just red-lined.

    Anyhoo, re the discussion on epilepsy and migraine-
    Tuberous sclerosis, an autosomal dominant disorder in which there are numerous developmental cortical malformations that lead to (often intractable and beginning in utero) epileptic seizures, is not associated with increased incidence of migraines, AFAIK.

    Another autosomal dominant disorder, neurofibromatosis type 2, often leads to the development of multiple meningiomas, which can cause pulsating headaches, and yet is not associated with epileptic seizures.

    I’m sticking with the meningeal-innervation-as-source-of-migraine-pain hypothesis, with the added consideration of pro-inflammatory cytokines released during or following epileptic seizures as a possible mechanism for a link with meningeal nociception.

  35. Rieux says

    To complete the tangent I started: I’m still on the same computer, I haven’t changed anything, and the post looks fine now.

    So I’m guessing harderkid13 or PZ changed the font and size. Either way, thanks.

  36. Stella says

    I have migraines, ophthalmic migraines (acephalgic migraines with bilateral scintillating scotoma) and a very mild seizure disorder. I had not heard of a connection between migraines and epilepsy before. Just that connection might be an interesting area for you to look at.

    After much experimentation with terribly expensive medications I found I could manage the migraines with caffeine, ibuprofen and dark chocolate, though some of those can trigger migraines in other individuals. I’ve also been tempted by the above-mentioned icepick solution, though I feel a hand axe might be a more thorough solution.

    The scintillating scotomas can be quite gorgeous and marvelously entertaining. One of these days I’m going to set one to music.

    This seems to be an area where much remains to be discovered.

  37. nihil says

    So what about this: I don’t get migraines (I don’t think they’re migraines), but I sometimes get pretty bad headaches that are associated with muscle tension in the upper back of my neck. If the headache is on the right, then sure enough there’s a knot to the right of my spine, and if it’s on the left, there’s a knot to the left. I can geive myself these headaches by lying on my neck badly (my dorm room couch was horrible for this), and getting someone to rub my neck really hard helps, although so does ibuprofen. I always wonder why I feel the pain in the front, just above my eye when the source is in the back, below the end of the skull.

  38. says

    nihil: I get those exact same headaches. Because the pain is all on one side of my head, my doctor diagnosed them as migraines and gave me Imitrex, which works great (good thing, because no OTC pain relievers get rid of these). When I take the Imitrex, within about 15 minutes or so, I get a distinct sensation that feels like the pain just flowing right down out of my head.

  39. Hank Fox says

    I’ve noticed I can occasionally experience pain at some distance from the real disturbance — for example, a tweak in my upper back might be felt as a dull pain in my hip.

    I get the occasional headache that I’m convinced is happening in the nerves along the surface of my skull, but which feels as if it’s somewhere in the right-front-center in the interior of my skull.

    With this and other bits of evidence, I’ve speculated many times that there might be a sort of holographic element to pain perception.

    Local nerves can pinpoint the sharply-localized origin of a sting, but for pain that spreads over a larger area, the pain becomes more of a pain SHAPE in your head. And depending on where the nerves that detect the original disturbance are situated, that shape might appear to place the pain … either somewhere else, or in the center of a 3D area of origin. In other words, pain in the nerves along the exterior of your skull could generate the perception of pain INSIDE your skull.

    The idea could account for phantom limb pain. The foot might be gone, but the nerves in the remainder of the leg, which are still “upstream” of the foot, just as they were when it was there, are still capable of helping to generate the sensory hologram of a foot, causing you to experience pain IN the nonexistent foot.

  40. bfish says

    If we’re sharing migraine stories, I apparently get them without headaches, like a couple of people above. I just experienced my putative second migraine, after a seven year hiatus, and spent two days in the hospital getting tested for this and that. (Including for patent foramen ovale, as mentioned in Comment #3 – thanks for that!). The first time it happened, I suddenly couldn’t make out any words in a newspaper for about two minutes. In this latest event, I had a few minutes of aphasia. Here is the complete text of an e-mail I typed to colleagues in my lab: “Then this seem the seems some come again.” Somehow I had enough clarity of thought to know THAT wasn’t right! Both now and seven years ago I also experienced tingling or numbness in one hand. Diagnosis then and now is the aura of a migraine.
    The brain is a funky monkey.

  41. NelC says

    Scintillating scotoma, Batman! So that’s what they’re called. Over the last ten years or so I’ve had four or so of those, most recently about a month ago. I figured after the first one that they were probably migraine-related, though I had no pain, luckily. Pretty light show for about a half-hour as it expanded from a small speck out to the edge of my visual field. I think it was fixed to one eye, but my experiment with crossing my eyes last time was inconclusive.

    I have had lots of minor bashes to my head, since I’m quite tall and I live in a country with a lot of old, low doorways. They’re usually to the top of my skull, though. Does the visual cortex reach up there?

  42. Paula Helm Murray says

    Back once upon a time when I worked at a veterinary vaccine manufacturer who is now defunct, I started having migraines. I had about 60 minutes once I started having symptoms before I became incapacitated and unable to drive. And I lived about 30 minutes away.

    My Evil Doctor(tm) (since fired) was gleeful and wanting me to take tons of tests and start taking strong drugs. She envisioned a long-term money trail.

    The headaches quit when I quit the job. On looking back (I did keep the occurances on a calendar) the migraines coincided with the deactivation of bacterins (bacterial vaccines). They use formalin to do that. I’m Very Allergic to formalin, discovered that in High School biology dissection. So while touching it gives me hives having it in the air gives me migraines.

    It did serve to give me much sympathy for migraine sufferers. It’s the most miserable headache I’ve ever had (and at full flush, some barfing was involved).

  43. Lindsey says

    I have also taken anti-seizure medication for my migraines. I tried the customary anti-depressants (since everyone is depressed these days) my Dr. recommended and they did not work. I also tried muscle relaxers. Finally they started me on topamax and it worked wonders! I took a low dosage for about 6 months and now i only get 1 or 2 a year and they are not as severe. Strangely enough, soda tasted metallic the entire time I was on that drug… Now I take zomig whenever i get one and it usually works. I also have an interesting variation of an aura – i have smell hallucinations! I think I smell something like cat food that is not there. It never fails that I get a migraine the next day… weird. These days I blame my headaches on being a graduate student. ;)

  44. Viscous says

    I also get the scintillating scotoma with no pain. I thought this was
    highly unusual (that’s what doctors always claimed), but judging from the
    number of people here who report the same thing, I’m wondering if this is
    actually quite common. Perhaps it is not even the same phenomenon as
    migraine, but is just related to migraine somehow.

    There is an interesting, but highly dated, book about migraines written by
    Oliver Sacks. “Migraine”, originally published in 1970, revised in 1992.
    You wouldn’t be able to find a copy except for the fact that Sacks got
    famous for his other books, but it contains lots of interesting anecdotes
    and some fascinating pictures drawn by people to illustrate what they see
    during an attack.

  45. JohnnieCanuck, FCD says

    Me too, scintillating scotoma that is not always followed by a headache. Mine are not severe enough to warrant medication, beyond maybe an Ibuprofen.

    That first one, when I had no idea what was happening, was during a job interview. I was being shown electronic schematics on 22 X 34 inch sheets that I couldn’t see, except around the edges of my vision. Pretending that nothing out of the ordinary was happening added greatly to the stress. Fortunately there was no debilitating headache to really mess things up.

    NelC, cover one eye at a time and see if you can read anything behind the flashing area. For me it is both eyes, with the area of blindness starting just outside the boundary of the scintillation. BTW, for those who haven’t experienced it, the blindness is much like that associated with the well known anatomical blind spot and filled in by the brain, just bigger and variable.

    There’s not a soul on this planet that hasn’t had a bump to the head, migraines or not. Short of being able to make a correlation with some diagnostic level of damage, like concussion symptoms diagnosed by a doctor, forget it.

  46. Stephen Wells says

    Re. the passing comment about the pain “not being real”- I’m pretty confident that any pain you are feeling is, in fact, a real pain. It isn’t a real _injury_, perhaps, but the sensation of pain is as real as pain gets.

  47. Barn Owl says

    The sensation of pain does not require gross injury, and nociceptive sensory neurons respond to a variety of stimuli: bradykinins, prostaglandins, K+ and H+ ions, edema, distension, irritant aerosols, capsaicin, noxious thermal, etc. Adequate stimulus of these sensory neurons is transmitted to the brain via spinothalamic (trigeminothalamic in the head) pathways for perception of pain in the cortex. It seems to me that any of the neurological events associated with migraines (described by those who have migraines, in the comments above) could produce adequate stimulus of trigeminal nociceptive neurons, whose cell bodies live in the trigeminal ganglion, and whose peripheral axons are distributed to the meninges and walls of large blood vessels inside the skull (as well to the face, teeth, sinuses, etc.). IOW, the pain experienced by migraine sufferers is very real.

    FWIW, adherence to irrational and unsubstantiated beliefs about medical issues, which appear to arise from a lack of understanding and knowledge of basic neuroanatomy and neurophysiology, reminds me of religion.

  48. Science Goddess says

    On the subject of headache pain: I received a liver transplant in 1989 and the resulting prednisone dosing gave me really wonderful migraines. Haven’t had one since dropping the pred in 1993. But for REAL headache pain you should try cryptococcal meningitis. That topped migraines by several orders of magnitude.


  49. says

    So, were any of you migraine sufferers ever hit in the head when you were children.

    Nope. It’s entirely genetic for me – from my grandfather to my mom to my sister and me, and, unfortunately, now to my 9 y.o. son. He just had his first migraine on Tuesday.

    Genetics can suck.

    I’ve tried many prophylactic drugs, from beta-blockers to seizure meds (topomax & depakote) to barbituates (bellergal); right now I keep the headaches in check with a skull full of botox shots every 3 months (which reduces the severity, but not the number, of headaches), plus zomig nasal spray at onset of headache, plus percocet if the headache comes back after zomig.

    Nothing but fun.

  50. sailor says

    On phantom pain. It is true that there are no nerves to send any pain signals any more. However, the receiving end for those signals in the brain is still there. So if it starts responding to signals from some some other source (there area a lot of connections after all) it would still be felt as a sensation.

  51. Rob Rusick says

    Hank Fox @45: When I had a beard, I used to be able to tug on one hair in particular, and feel a twinge in the root of one of my teeth.