so there has always been a market for analgesics or pain-killing remedies.

Ancient Egyptians munched on myrtle leaves and smoked opium, Native Americans chewed up strings of willow and birch bark to dull their pain.

Today there are all sorts of pills that could make painful situations more bearable

but to understand how these things do their job,

it helps to first get a handle on why we have physical pain at all, how it works

and why we feel it so often like right now, the lights... in my eyes... its been a long day

Although most of us go to great lengths to avoid it,

pain is good for us because it helps us protect ourselves from the world!

Pain means the body is damaged or under distress. It keeps us from doing stuff

that is not in our self interest by making that lack of self interest very obvious

"Ouch!" is your brain saying "STOP!! Back away from the flame or porcupine or wasp nest

before you suffer further damage."

and it's often the earliest sign of when our bodies are under attack by disease.

This is why one of the most dangerous, but extremely rare conditions can be an inability to feel pain.

Take, for example (United States) Georgian teenager Ashlyn Blocker

she has a mutation on a gene called SCN9A, that

has left her with a congenital insensitivity to pain.

She's run around on a broken ankle for days

fished dropped spoons out of pots of boiling water, and nearly chewed her own tongue off accidentally.

Sometimes other medical conditions can interfere with the body's ability to feel pain.

The bacterial infection, Leprosy, for example, leaves infected nerves and tissue dead.

So contrary to lore, leprous fingers don't just fall off,

rather they sometimes sustain great damage because they're numb and have to be amputated.

Thankfully, conditions like this are exceptionally rare because our whole nervous system is

set up to make sure that pain is the first response to any damage to our bodies.

Our nerve receptors are constantly picking up on all kinds of sensations, but we've got specialized receptors called Nociceptors

that unlike those receptors that help you enjoy kitten kisses, only fire to indicate pain.

For example, if you hold a needle lightly into your palm, you can feel the point, but it doesn't hurt

because only your normal nerve receptors are reading the needle.

But if you start slowly pushing on the needle, at some point, it'll hit the nociceptive threshold

and then...Ow!

The pain hopefully makes you stop digging the needle into your flesh.

Now if the pain is the result of something more severe

like tissue or cell damage from falling on your tail bone or slicing your finger on the can opener

your body starts sending waves of tuning chemicals to your bruised bum or bloody finger.

These chemicals lower your nociceptor pain receiving threshold even more.

That's why if you touch a cut or other open wound BARELY, it hurts more.

Those tissues have higher levels of tuning chemicals that warn against further damage.

Kind of like adding insult to injury, I know, but these chemicals are not only the root causes of our pain,

they're also the targets that scientists look for to kill the pain.

Think of these compounds as locks and keys.

One of the main chemicals that damaged cells release into your body is called arachidonic acid.

Its job is to interact with two enzymes known as COX-1 and COX-2.

When the arachidonic acid combines with enzymes, they form compounds that do things like

cause swelling, raise your body temperature and heart rate, and lower that pain threshold

everything that we associate with being hurt.

So if we can keep the arachidonic acid from being the key that fits into those enzyme locks,

we can control the effects that these chemicals cause.

To do that, we send in pain killers to block those locks.

And they fall into two main categories:

First, you got your friendly hardworking, over-the-counter variety.

You'll find them in your medicine cabinet, purse, or tiny package of two pills at a gas station for like five freakin' bucks.

The second family is made up of the big gun Opioid drugs.

The kind that only doctors can prescribe, like morphine and oxycodone,

the ones that people keep getting addicted to these days.

You're not popping these babies for a little headache. They're for severe, nail-through-the-foot, hernia surgery, crap-oh-crap pain.

The first over-the-counter group is known as Nonsteroidal anti-inflammatory drugs, or NSAIDs.

They block that flood of pain chemicals, but they don't know exactly how to find the exact site of the pain,

so they just block all of those pain signaling Cox enzymes, preventing them from sounding the pain alarm.

Aspirin, also known as Acetylsalicyclic Acid, was first isolated by German chemist, Felix Hoffmann in 1897

for the Bayer company, and its key pain relieving compound is Salicin

And that is found in that Willow Bark that our ancestors were munching on back in Hippocrates' day.

Salicin metabolizes into Salicyclic Acid, which disables the Cox-1 enzyme particularly well.

Here, Aspirin is working like a key that breaks off in the lock, that blocks all other keys from getting in.

This means no pain-increasing arachidonic acid gets into the enzymes,

which means no pain for as long as those blocked enzymes are in your system.

Ibuprofen, often marketed as Advil and Motrin, was first derived from Propionic Acid in the 1960s

as a treatment for Rheumatoid Arthritis

and it works a little differently from other NSAIDs.

It blocks arachidonic acid from getting into the enzyme sights responsible for pain, but rather than permanently breaking off like aspirin,

Ibuprofen just sort of sits there for a while and is eventually spit out by the enzyme block.

Naproxen Sodium, including the drug Aleve, is another class of NSAID that also works by inhibiting Cox enzymes.

Finally, Acetaminophen, or paracetamol, commonly branded as Tylenol, is an over-the-counter drug

that is not an NSAID. It only takes effect after the tuning chemicals have bonded with the enzymes

and it inhibits some, but not all, of the effects caused by the compounds they form.

That's why it helps relieve pain and fever, but doesn't reduce inflammation.

Acetaminophen is made from coal tar and is mostly metabolized in the liver

So, yeah, if you have too much of it, it can do some liver damage.

So..be careful.

But sometimes pain might transcend anything your medicine cabinet can ease,

after, say, your friend accidentally backs over your foot in their mini-cooper.

That's when you might want to see a doctor about some prescription pain killers.

Opioids do business in a completely different way from NSAID's.

They're kind of like silver-tongued pep-talkers, and humans have been using them medicinally and

recreationally for thousands of years.

Truth be told, they don't actually kill pain, they just make you forget about it

as you drift off into a cloud of numb.

They relieve suffering by blocking the transmission of pain signals to the brain,

And then by massaging the brain's opioid receptors to alter its perception of pain,

whispering, "Everything's cool, man. Just relax. Sure, you're bleeding all over the place, but it's no big deal."

There are three types of opioids: natural opiates, semi-synthetics, and synthetics.

Natural opiates, like morphine and codein, are derived right from the old Opium Poppy Plant.

Not a coincidence, by the way, that Dorothy and her friends got all sleepy and chill in that

poppy field outside the Emerald City in Oz.

Morphine is the active ingredient in Opium, and it was first extracted in its purest form

in the early 1800s, to become the most commonly used pain killer during the Civil War

Before that, fainting ladies sipped Laudanum, or opium diluted in alcohol to calm their nerves.

So lots of people were enjoying the mellowing effects of Morphine a little too much.

So in the 1870s, chemists started working on an alternative, and they came up with a doozy, about

twice as potent and equally addictive: Heroin.

Heroin lives in the Semi-Synthetic Opioid branch of pain killers right next to other highly-addictive

prescription bad-boys like Oxycodone.

Chemist C.R. Alder Wright created heroin by adding two acetyl groups to a naturally occurring morphine molecule

When used medicinally to treat extreme pain, its known as Diamorphine.

When its used illegally on the streets, its called smack, dope, H, junk, etc.

and you can watch The Wire to learn all about it

By 1905, things were bad enough that the US Congress banned opium and soon passed

the Pure Food and Drug Act, which required medicines to list their contents on a label

Crazy!

Still searching for a powerful but less addictive painkiller, in 1937, German chemists synthesized Methadone

Methadone works by hitting up the same opioid receptors as the morphine and heroin

and belongs to the fully synthetic arm of the opioid family

which also includes stuff like Demerol and Fentanyl

So Methadone is used to treat addicts easing off heroin

but many believe it is equally - if not actually more - addictive

So while opioids definitely have their place in pain management

they can be a slippery slope. Their side effects may include nausea, drowsiness, constipation

and, if abused, your life going down the toilet

For this reason, among others, researchers keep looking for alternative ways to ease our pain

One unusual source of a new potential pain killer...

Snake Venom.

Like Beatrix' kiddo wielding a Hanzo sword, the black mamba

is one of the world's deadliest assassins - its super potent venom could handily kill you

in less than an hour. But recent research has found that black mamba is actually

a gentleman killer because its deadly neurotoxin is spiked with Mambalgins

I don't know how to pronounce that

But it is a painkiller as potent as morphine that eases the exquisite pain of impending death

Consider it!

But mamblgins use a different mechanism than anything we've covered so far

while morphine binds to opioid receptors,

mamblgins zero in on the pain-sensing nociceptors themselves

right there at the source.

There are several advantages to this, like whereas opioids have dramatic side effects like

slowing down your breathing, mambalgins don't - and they're less addictive

A French pharmaceutical company is currently developing a "Mamba-drug"

and more power to 'em

As quick as we are to reach for the Aspirin, without the sensation of pain,

the world becomes a dangerous place

Pain is, in many ways, a gift

So next time you're running up the down escalator and fall and slice your knee open,

put aside your humiliation and thank that escalator and your angry pain receptors

for reminding you to watch your step and work on your self preservation

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