If you’ve ever stepped on a LEGO brick  or shoved a piece of pizza in your mouth, you might think you know pain.

Don’t get me wrong – it takes some  grit to survive stubbing your pinky toe on a coffee table, or even more  if you accidentally fracture it. But, scientifically speaking,  there are some medical conditions that hurt more than a stubbed toe.

Like, a lot more. [♪ INTRO] Pain can range from annoying to  unpleasant to life-changingly awful. And before we get into five of  the most painful conditions, it helps to understand why pain is  hard to measure in the first place. Biologically, pain is a way  for your brain to tell you, “Hey, something bad is happening!” It’s a sensation that helps us protect  ourselves from dangerous things.

Your nervous system carries all kinds  of messages throughout your body, including sensory information about the world. And you have specialized receptors  linked to different senses, like photoreceptors in your eyes  or taste receptors on your tongue. Nociceptors detect various  kinds of damage to your body.

When nociceptors are activated,  they send signals to your brain, which interprets those signals as “ouch!” That word interprets is the key. There isn’t a “pain signal” that  can be measured in nerve cells or dialed up or down like the volume of a speaker. Pain is a subjective experience that all of our brains process in their own personal ways.

So when doctors talk to patients  about their experiences, they use tools like visual scales where  you can point to different kinds of “ouch” faces, or numerical scales where  you rank the pain you feel from 0 to 10, with 0 being “No pain at all” and 10  being “The worst pain you can imagine.” But one person’s 3 on a pain  scale could be another person’s 7! Because there isn’t really a  universal standard for pain, lots of people end up describing  their pain with metaphors, which make their way into medical  records and scientific papers. Even though your head isn’t literally on fire, or you don’t have a knife lodged in your arm, you might describe pain as “burning” or “stabbing” to help express the intensity  of what you’re feeling.

All this to say: there might not be an  objectively most painful experience, since everyone will have their own answer. So to present you with five  of the most painful diseases, we’re really talking about “five  things that seem extremely painful based on aggregates of subjective experiences.” That said – these five almost certainly  crank the pain scale up to 11. We’ll start with a bang – or, more  specifically, a thunderclap headache.

This headache is extremely sudden,  like a crack of thunder in a rainstorm, with intense pain ramping up  in less than 30 to 60 seconds. And it doesn’t seem to have an obvious cause, like being congested from a cold or staring  at your computer screen for too long. The term “thunderclap headache” was  first coined in a 1986 case study about a 42-year-old female  patient who had three of them within a week and said they were  "like a hammer hitting her head." Since then, other people have described  it as “the worst headache ever.” And thunderclap headache is treated  as a medical emergency where doctors need to run more tests, because  we think that it could be a warning sign of another  serious brain-related condition.

That 1986 case study was looking  at a link between severe headaches and cerebral aneurysms, where blood  vessels in the brain get weaker, balloon outward, and potentially  burst open or rupture. Specifically, they found an unruptured  cerebral aneurysm in their patient, which they were able to treat  and seal off before it got worse. But the intense pain of a thunderclap  headache could also mean that a blood vessel in your brain  did rupture and start to bleed, that there was a change in the  fluid pressure in your skull, or that there’s a clot keeping  blood from flowing to your brain.

Since your brain needs the right amount  of blood flowing in the right places to deliver oxygen and keep everything working, it’s pretty dangerous if  any of these things happen. Basically, I can’t actually give medical  advice, but if this happens to you, the ER might be where you need to go. Now, you can’t have thunder without  lightning, so it’s only fitting that there’s also a super painful condition called  trigeminal neuralgia, which patients have described as “a ‘lightning bolt’ to  the face” or “the world’s worst pain.” It’s a sudden, severe, piercing  pain that’s focused anywhere along the trigeminal nerve, which is the  largest nerve that runs beneath the skin of your face and controls many of  your facial muscles and sensations.

Basically, the trigeminal  nerve is how you can chew a bite of brownie or feel  a soft kiss on your cheek. And, unfortunately, trigeminal neuralgia can turn even the gentlest touch to  lightning-bolt-level agony. This condition was originally called  tic douloureux or “painful tic” by the French physician Nicolas André in 1756.

He was studying ways to surgically help patients who experienced intense pain and facial spasms. By listening to patients and  poking around surgically, he deduced that some kind of pressure or damage to facial nerves was the  root cause of tic douloureux. But his treatments were pretty  gruesome by modern standards, since they involved cutting open a  facial wound and not letting it heal.

This prevented the nerve from getting  re-squished and being oversensitive. Nowadays, we think trigeminal neuralgia  has a couple different causes: direct nerve damage from a surgery or an injury, a blood vessel pushing on the nerve, or a  different disease like multiple sclerosis that causes the protective  coating on the nerve to wear away. And, thankfully, our modern treatments are more sophisticated than those of 18th century France.

They include surgeries that try  to reduce pressure on the nerve, or medications that can reduce how  much the trigeminal nerve is sending all kinds of signals –  including the nociceptor ones. These treatments can’t  always make the pain go away, but they can make it a little easier  to feel a breeze or bite into a donut. Thanks to Brilliant for  supporting this SciShow video!

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Plus, you’ll get your first 30 days free! There’s also a super painful group of  disorders called hypercontractile esophagus, which can affect your ability to swallow food. And if that medical name  doesn’t roll off your tongue, there are two less-stuffy terms: nutcracker esophagus and jackhammer esophagus.

These disorders involve unusually  strong muscle contractions along your esophagus, from your  throat all the way to your stomach. We’re not entirely sure what  causes jackhammer esophagus, but it’s something weird with  your nerves, muscle fibers, or the neurotransmitters that help  them communicate with each other. The severe chest pain that goes along  with these uncontrollable contractions can feel like intense squeezing, and the pain can radiate out to your neck, arm, or back.

It can also be mistaken for a heart  attack or come with intense heartburn. The term “nutcracker esophagus”  was first used in research papers in the late 1970s or early 1980s to  describe non-heart-related chest pain that was linked with extra  strong esophageal contractions. While we can’t measure the pain signals, we can actually measure swallowing using a technique called esophageal manometry.

Basically, it involves sticking  a narrow tube down your throat that gets squeezed by your  muscles and records the pressure. From this, we know that nutcracker esophagus kicks swallowing up a notch – hence the pain. But doctors realized that there  were some people whose swallowing was even more extreme and painful  than nutcracker esophagus, sometimes even with spasms.

So around 2012 they coined the  term “jackhammer esophagus” as the new king of this group of disorders. To treat this kind of pain we usually  try to reduce the intensity of these contractions wherever possible  by blocking some – but not all – muscle action through medicines  or even botox injections. Because you have nerves all over your body, majorly unpleasant nerve  damage can happen anywhere too.

That’s the underlying problem of  complex regional pain syndrome, or CRPS. Its major symptom is a disproportionate  amount of pain that can get triggered by pretty much anything, from wearing a scratchy fabric to just  trying to move your body. Plus, a limb with CRPS can  swell up, get unusually sweaty, have unusual hair growth, lose  muscle or bone, change color, or even start looking like scar  tissue – because nerves help control all these processes and more.

There’s been documentation of conditions  sort of like CRPS for hundreds of years even if people weren’t using that exact term. In 1813, for instance, a British  surgeon described a soldier wounded by a bullet in his  arm, who seemingly healed, but had a lingering, violent  pain “of a ‘burning’ nature.” The surgeon actually compared  the symptoms to tic douloureux – that old French term for trigeminal neuralgia. Or in 1864, an American Civil War  doctor named Silas Weir Mitchell described soldiers who suffered  from chronic burning pain after their gunshot wounds seemed to heal.

And he named it causalgia. We eventually landed on  “complex regional pain syndrome” as a name and two main diagnoses. CRPS-2 is more straightforward  – it’s a result of nerve damage, like from surgery or all those gunshot  wound case studies in the past.

But there’s also CRPS-1, which sets in  after illness or injury even if nerves weren’t directly damaged, possibly  because the immune system did something weird while healing and your nociceptors  become extra sensitive in the process. Unfortunately, because we don’t  fully understand the causes of CRPS, it’s hard to treat it – other  than trying to reduce pain with medication and physical therapy. That American doctor Silas Weir Mitchell  kept plenty busy studying nerve damage, and he wrote about our fifth  condition in an 1878 paper.

Erythromelalgia causes extreme, burning pain and bright redness in patients’  extremities like hands and feet. This condition is also  nicknamed Man on Fire Syndrome, which pretty much explains all you  need to know about its intensity. A flare can be triggered by anything  that gets your blood pumping or warms you up, from exercise to spicy food.

One patient has described flares  “as if they’re placing their hand on the burner of a stove” or “like  walking across hot coals.” The causes are still a little mysterious,  but we think some patients have a mutation in a protein called  a voltage-gated sodium channel, specifically one named NaV1.7. Sodium channels in general help nerve  cells communicate with each other, and we think NaV1.7 channels  are specifically important in nociceptors and sensing pain. In patients with Man on Fire Syndrome,  we see overactive forms of NaV1.7, which means their nerves are  signaling more than normal, and lead to the brain screaming “ouch!” even when there isn’t a damage-causing sensation.

To treat erythromelalgia, patients  are given medications that can numb or reduce the pain in some way by  interfering with nerve signaling. And even though some people try  to use ice baths to counteract the burning sensation, that can be dangerous,  because you might damage your skin even worse with the cold. So it’s sort of a lose-lose situation.

All five of these extremely painful  medical conditions rely on researchers and other professionals to believe  patients when they say something hurts. Because pain is subjective, we have to  trust the people who are experiencing it. Many of these painful conditions  are also rare, and fewer patients mean fewer opportunities to study  them and find treatments that work – or for these patients to find  community with other people who get it.

So, as with everything in  science, the work continues. And anything we can do to demystify how  pain works and how the nervous system can go wrong will probably also reduce  the suffering these people endure. [♪ OUTRO]