The Future of Pain

a kind of upsetting subject today. It's great, but it's universal. It is. We're talking about pain. Yeah, the future of pain and of pain management, of counter pain, you might say, yes, more of an emphasis I think on on you know, trying to prevent pain. We're not just talking about the future of causing causing pain, right because Okay, there's been a lot of sad news lately about the increasing rates of pain medication over use or abuse and the tragic

consequences thereof. Yeah, I think a lot of this came in the wake of Prince's death recently, which I know has been linked in the media to uh to use of an opioid drug to treat chronic pain. I believe, yeah, I think. I think his official cause of death has been listed as an accidental overdose of fentanyl, which is this opioid pain relief drug. But but I mean Prince aside, and that was certainly tragic. We all miss Prince um. But the problem is is very widespread and very serious.

Some some numbers for you guys. According to the CDC, in the United States alone, in over fourteen thousand people died from overdoses involving prescription opioids UM. A national survey that same year reported that almost two million Americans were abusing or physically dependent on prescription opioids, and a thousand people go to the emergency room in this country every

day for misusing prescription opioid drugs. Opioid. I'm sorry, that's a funny sounding word to say it is, Isn't it like a like the name of a pet, walrus or something. It sounds like fiords. It's got that eel in it. It reminds me of the of the nerd from Dominoes. For some reason, I'm not sure why the nerd the noid anyway, at any rate. Yeah, of course, opioids are are a class of drugs. They contain drugs like morphine

and all those opium derived drugs. We'll get into more of the specifical thing, Yeah, more of the specifics of that lately. But yeah, this is obviously a huge problem. But it's not just a problem that people are overdosing on these drugs. I mean, pain is a big enough problem on its own to merit some sort of intense solutions. Oh. Absolutely, And we're not trying to put out a DARE episode here, I don't. I don't know if you were in the DARE program when you were in high school. The the

drugs are are rotten, all y'all. I that's not an acronym, but they're rotten, so you should get some fresh ones. They've gone off. I'm mostly impressed that I just tried to make the E and DARE stand for all y'all um. But yeah, we're not. It's right, it's not just a drugs are bad problem. And and furthermore, it's not just kids that are abusing these drugs. It's a range of ages of humans who are doing it. Um. And and the problem, of course is that medical science has not

figured out how to solve pain yet. Yeah. Pain, surprisingly, despite the fact that we do know some things about it, it is in many ways an open problem in medical science. We have some ways of treating it. Obviously, the best thing to do to address pain is to go in and fix the problem that's causing pain to begin with.

But then there are lots of issues that will talk about, such as chronic pain, where in many cases you've sort of lost track of what the original causes and now you're just having the subjective experiential problem of distress and and unpleasant feelings. Uh and and what can you do but treat the feelings themselves at that point? But yeah, so pain is a pain is a big problem. Pain is a big problem all over the world, in the

United States alone. In a report in the Journal of Pain, good journal name tried to calculate pain, but it tried to calculate the cost of chronic pain in the United States. And chronic pain has costs, of course, not only because you have to pay for the treatment. The drugs cost money, the doctor visits cost money, but because it complicates treatments

for other medical conditions. Say, for example, if if you've got chronic pain, Your your your outlook for a different kind of condition might be different because you've already got this other problem to deal with. You might not be able to take the drugs or get the surgeries or something like that. Uh two that you would need to deal with this other condition. And also because workers tend to lose productivity as they experience pain, the more you hurt,

the less you have to offer. Often. I mean not to say you're any worth any less as a person, but sure, but it's just different cuts into your ability to do things. Yeah, yeah, absolutely So they in this study estimated that every year chronic pain costs the United States between five hundred and sixty and six hundred and thirty five billion dollars, which is actually more than the

estimated annual costs of cancer, diabetes, or heart disease. So, I mean, it's pretty much a no brainer that we should be focusing our efforts on finding ways to solve the problem of pain. But that's a lot easier said than done. Sure, but coming down to the to the basic factor that we we don't have a complete concept of what pain is. Yeah, it's kind of hard to get underneath pain and define it. Isn't it like it's

such a basic subjective feeling. Pain almost seems like the thing by which you describe other things is not a thing that you describe unto itself. Because it's one of those baseline experiences of being a human being that it's just hard to put your put your mind around it.

But to give a basic definition, a task force for the International Association for the Study of Pain did try to give a pretty universal medical definition of pain, and it's the one I've seen sided most often, and it goes like this quote, pain is an unpleasant, sensory and emotional experience that is associated with actual or potential tissue damage or described in such terms. Uh So, that's basically

just saying like pain hurts and is upsetting. Yeah, and that emotional part, the upsetting nous is crucial, and I want to talk about that more towards the end of the episode. But in addition to this really basic definition, usually doctors and medical professionals are going to divide pain into two, uh basic, very different types, which are acute pain and chronic pain. Right, so let's let's start with acute. Yeah, Acute pain is the kind of pain that everybody is

familiar with. It's a temporary result of disease, injury, or inflammation, and it's good. It warns you that something is wrong, and for this reason it is quite useful, especially in today's medicine. So in an evolutionary sense, acute pain is useful even you know, if you can't get to a doctor. It's useful even in the wild, because you might, for example, stop putting weight on that injured leg of yours because it hurts when you do, and that gives that leg

time and ability to heal. Without you continuously putting stress on it is just going to make the problem worse. Sure, Or if you touch a hot surface, yeah, you remove your body apart from it immediately because it hurts, preventing further injury, as opposed to just leaning on I don't know what's that hot surface. Our our caveman versions of ourselves are encountering really hot rocks. I mean fire is bad,

so yeah, pretty but bad. To stop getting struck by lightning, that's the fourth time this week, exactly, I gotta stop climbing up this tree. Uh but yeah, So in fact, they're there're certain recognized conditions that prevent people from feeling pain, and that's not a good thing. Obviously, that sounds great because we don't like pain. But you need your pain.

You need this. It's very important to very useful trait. Exactly, people who are born without the ability to feel pain have what's known as congenital analgesia, and it is very dangerous. People can suffer injuries or illnesses without being aware of them. Uh, and then those illness, illnesses, injuries, whatever, the bad state can progress without treatment and lead to disability or even death. And if you have congenital insensitivity to pain, you have

to be on the lookout all the time. You have to be extremely vigilant of what's going on with your body because you're it's not going to let you know when something is wrong. You have to basically scope. You have to observe it right right, You're not a leg is bent sideways and you're not going to feel that splinter in your foot. You're you have to find it. You have to notice it in other ways. So acute

pain is good and useful, but of course it's not useful. Say, well, you know, once you're already aware of the disease, if you've got a broken bone or something, you probably will need some pain killers to deal with that, and we have pretty good remedies for that, right. Yeah, Acute pain is a category of pain that we're we're usually pretty

good at treating these days. You know, like if you've got sinus pain due to inflammation because of an infection, you could be able to treat the infection, uh, and you can definitely take an anti inflammatory to treat the cause of that pain. If you've got a knee injury, you can help the leg return to normal function faster, again treating the cause using you know, a brace or

physical therapy or again anti inflammatories. And you might also you might also be prescribed like muscle relaxers or electrical stimulation to lessen the pain while the knee heals. All of these are are you know, wonderful modern treatments and and has offer all of that. Um uh. But but the other type of pain, chronic pain, is a little bit more troublesome. Yeah, this is where things get really hairy. So long term and for the most part, pointless pain

is chronic pain. What what does long term mean? Some say longer than three months. I've seen longer than six months, So I guess we could say longer than three to six months might be an approximate general rule. But the idea is pain is chronic if it lasts longer than the healing time for the problem that's causing it. Ah yeah. And and these are again, these are the types of issues that we're not so great at treating because often

we don't have fixes for them. They sometimes involve damage to the nervous system itself, or or ongoing tissue damage due to some kind of bodily system dysfunction that we can mitigate but not necessarily cure, as in a cancer, arthritis, And so in these cases we're really just treating the symptoms, not the cause. Yeah. So let's look at the cause of pain. Uh yeah, because we've are amazing modern medical concept of it has not been around forever. Yeah, that's true.

Perhaps unsurprisingly, ancient people often interpreted pain through a magical or spiritual lens. Who would have guessed, uh, it was an affliction, you know, it's a punishment, something being done to you by another worldly agent. Very common to look at pain in these terms, and this type of thinking is still somewhat reflected in the origins of the English word pain actually, which comes originally through the Old French, but originally from the Latin poena, meaning punishment or penalty.

And in the earliest uses of pain in English we still see this connotation, like if you go back to the thirteenth century, say, to look at how pain is used in English, you'll see uses like if you hunt in the duke's private forest, it is a crime punishable on pain of death, meaning you get the death pen punishment of death. Yeah. I had never thought about that before. Yeah, pretty creepy, hunh. So when you have a pain in your in your eyeball, why did I pick eyeball? That's

a terrible thing. Do you have a stabbing pain in your eyeball? It is a punishment from someone. To be fair, if I had a stabbing pain in my eyeball, I would pretty much assume that anyway, even with science. But how fragile science is. But then, of course that you get to the ancient Greek physicians, and they sometimes wrote about pain as being a result of some form of imbalance or disorder or unnatural state. And this is a

very Greek way of thinking. I think we're going to get into the humors again, aren't we, Yes, Yes, so health and pleasure were created by order and harmony, things being balanced and in their natural state. Pain and displeasure were created by chaos and unnatural corruption, or things being imbalanced or out of order. And this general philosophical orientation, I think informed their literal understanding of the medical causes

of pain. So I want to read a quote from On the Nature of Man, which is an ancient Greek medical treatise in the Hippocratic Cannon, not written by Hippocrates, but part of his school of thoughts. So it goes like this. The body of man has in itself blood, flim, yellow bile, and black bile. These make up the nature of the body, and through these he feels pain or

enjoys health. Now he enjoys the most perfect health when these elements are duly proportioned to one another in respect to compounding, power and bulk, and when they are perfectly mingled. Pain is felt when one of these elements is in defect or excess, or is isolated in the body without being compounded with all the others. Oh yeah, I hate it when my flim gets in my toes and causes them to ate exactly, So you've got flam in your toes and you don't have any you don't have any

black bile to balance it out. What are you gonna do? My toe is gonna hurt, I guess. So that's that's why I've got gout. It's not all those I think everyone is eating pastries. I think that's a common Yeah, we get Tracy and Holly on the line. What did they like, ancient ancient cured fish pastries. I'm sure cured fish pastries. I would try cured fish pastry. I'll speculate.

I'll say that's it. But eventually, of course, medical science came to understand beyond the idea of the four humors, And part of me thinks that that's only got to be a partial explanation, right, because they thought, okay, so in some sense pain is caused by an imbalance of humors.

But surely they didn't think that was what caused pain when you cut yourself, right, or maybe maybe because you're like losing blood at that point, and so, well about what about a pricking feeling that doesn't quite pierce the skin? I don't know, I mean that seems a little off, like it doesn't fit their model. Not quite. Yeah, I'm not sure that they had entirely thought this through, to

be fair, they were probably busy with other things. Yes, yeah, not to insult those of the Hippocratic school of thought, but yeah, no, no. If y'all are time travelers and listening to this, we respect you, right. But of course, like we were saying, eventually medical science did come to understand the crucial role of the nervous system in the

perception of pain. So, in a standard pain response to like a damaging stimulus and knife goes into your skin or something, sensory neurons throughout the body or in the place where you're getting damaged, called no susceptors set off a chain reaction that travels through the nervous system via electrical impulses, through the spinal cord and eventually up to the brain. And the brain is what processes your pain

and your reaction to it. Now, this is interesting. It's not just like you have one pain center in your brain. Multiple regions of the brain are involved in reacting to pain, illustrating how pain is sort of a complex phenomenon within our bodies. Is not just that one sensation, but a

state of mind. So it involves direct sensory information, you know, like Okay, this pain is thermal and it's intense, and it's on my left ankle, and then it involves emotions like I don't like that, that's bad, motivation, get away quick, and cognition like a plan for escaping this torch being held to your ankle or whatever whatever it may be. To make it a little bit more complicated, because clearly

we needed that here. A part of the issue and no susceptive pain, that this pain that results from injury are chemicals that you're damaged, tissue releases called prostaglandins, which a help boost the signal to your spinal cord that you know something's up, hey, warning stuff is going down. Um and and be they help regulate things like your your blood flow and you're clotting principles, So they're they're what causes inflammation around an injury. And more on that

in a minute. Um and I also wanted to mention here that there's a second type of pain in contrast to no susceptive pain, called called clinical pain or neuropathic pain. And neuropathic we can probably guess from that word involves the nervous system. Yeah, yeah, this is the pain that occurs even though there was no negative stimulation to the no susceptors. So either your nerves themselves have received damage or something has gone wrong in your pain signaling system somewhere.

It's like getting pain spam. Yeah exactly, It's just word salads full of pain spam, and and your brain is going like, well, crape, I still have to deal with this email, I guess. So, yeah, you don't really have a choice, do you. We can. We can route spam into a into a junk folder. If only we could do that with pain spam. Yeah, oh man, let's call let's call some science science dudes. Well, that may be part of our part of our solution profile later on.

So today we do have some comprehension of how pain works in the body, but we still don't know everything, right, But the more we learn, the better we can treat pain. One of the things that we're that we're learning about is how chronic pain changes the brain. And doesn't sound good. It does. It's not good. That's terrible, um for for reasons that we really don't understand very well yet. Chronic

pain creates changes in the brain's connections and chemistry. Yeah, so Most of the stories you hear about the plasticity of the adult brain are positive, but this one not so much. Not so much. Yeah, it leads to abnormal functioning that can increase the sensation of pain and the likelihood of emotional conditions like anxiety and depression, which is just a horrible, no good feedback loop. And and so this is one of the really big things that would be super rad to figure out, no doubt. So we

we certainly have these pain problems. Of course, you've got the more manageable acute pain pain problems. You know, you've got hurt. It hurts, and you've got to figure out a way to deal with that. But that's temporary. We've got sort of a handle on that. Then we've got these bigger problems chronic pain. Uh, the way chronic pain changes the way our nervous system works and all that. So what are our pain treatment options today? What are the things that are most often used by doctors and

by people dealing with pain to fix the problems. As we said earlier, there are some physical therapies, but but the drug therapies are what we wanted to concentrate on today. So I think the first category to consider is the nonsteroidal anti inflammatory drugs, which are like aspirin and like

the proof and stuff like that. We're pretty familiar with these, Oh yeah, yeah, they're They're the most commonly used drugs for acute pain because they work by by blocking the effects of a couple of particular enzymes that are necessary for your body to make those aforementioned prostaglandins UM that that caused the inflammation and and stronger pain signals to go to the brain. So that is how they work

pretty simple over the counter. Don't usually need a prescription for them, um, unless you get them in very very high doses or if they're mixed with something else. But yeah, moving over into the prescription category, you've got antidepressants and anti epileptics, which are sometimes used in in chronic and

especially in neuropathic pain. Both are actually really poorly understood in their mechanisms, like no one's really entirely sure how they work, but researchers think that the chemical actions of both might help block pain pathways, might help block those signals that are shooting around telling your brain that stuff sucks. UM and anidepressants, of course, have a bonus action of maybe making a patient feel emotionally better, which helps to

de stabilized that that feedback loop. Well, yeah, as we've established already, emotion clearly is part of the medically recognized profile of pain. It's not just sensory information on your ankle, it's it's your whole disposition towards it's your feelings about it as well, Shure. So antidepressants can help with that.

The category of drugs that we started this episode off talking about opioids, is the category that are that's the subjective of the most concern for a number of reasons, all basically boiling down to the facts that they're really effective at blocking pain and also that they have really dangerous side effects. We'll get into the side effects in a second. But how opioids work. Okay, so your body makes opioids. They are neurotransmitters that plug into particular neuro

receptors and relief pain. Yeah. Yeah, because your your body has a sort of internal dialogue, Gwen, pain is going on. There's like there there are pain amplifiers and then pain pain dampeners to sort of to regulate what's going on

back and forth between your nerve cells in your brain. Right, and so so this this is one of those pain relievers in your body, and opioid drugs work by plugging into those same neural receptors and producing similar effects yea, or not yea, because they're not quite the same as the opioids that your body makes, and those chemical differences lead to the unpleasant side effects that we see, right,

and so there are a lot of side effects. In fact, we should try to address as well as we can a sort of broad range of the problems with pain treatment options that exist in the drugs of today. One of the most straightforward ones, though it's probably worth mentioning, is simple inadequacy. Yeah, Like, a problem with a lot of pain treatments and medications is that they do not work, or they do not work enough. This maybe should go

without saying, but it's something to consider. You know, you might be taking a tile and all for your pain and find uh i k I already took the pill, but it's still really really hurts. It does not reduced the pain to a tolerable level, right, sure, or that your body develops a tolerance to it over time, in the case of opioids in particular. Yeah, And so another one of the big things is going to be side effects,

as you just mentioned. Yeah, and and even those over the counter nonstoridal anti inflammatories like aspirin should definitely be treated with care because they're they're known to cause pretty serious gastro intestinal bleeding, especially when taken regularly or along

with other acidic foods like like alcohol. Yeah, oh yeah, and so a lot of them come with those warnings, right, yeah, yeah, that's basically why it says not to drink and take it at the same time, because nobody wants your stomach to bleed, right. But then, of course the side effects of opioids are one of the big problems for concerns.

So according to a two thousand eight article in Pain Physician, most common side effects for opioids include quote sedation, Okay, that's pretty expected, but dizziness, nausea, vomiting, constipation, physical dependence, tolerance,

and respiratory depression. The most common of these being constipation and nausea, which in some cases, I mean, those sound like things that are bad but maybe in some cases preferable to intense pain to intense crazy pain all the time, depending on depending on the patient and the pain and that whole round of information. But then, of course, in some cases even constipation and nausea alone might be severe enough that the patient is just going to have to

discontinue use of the drug. And so in many cases, when you're treating pain with an opioid, you're going to have sort of an arms race going on, uh, fighting back and forth between is the opioid enough to fix the pain without the side effects getting so bad that they're worse than the pain itself. Yeah, which is which is of course the question in any drug treatment, but

is is particularly common in in opioid pain relievers. And of course the physical dependence and addiction are major concerns that make the make the opioids especially controversial when it comes to treating chronic pain. Sure, And and that respiratory depression is it's not a it's not a frenzies kind of problem. Yeah, that was the last one I mentioned in the list. It's not just like an uncomfortable feeling or an annoyance. Respiratory depression is the cause of death

in most fatalities due to opioid overdose. You stop breathing, That's what it does to your body. Uh. And according to the World Health Organization. In the United States of America alone, in two thousand and ten, there were an estimated sixteen thousand, six hundred and fifty one deaths due to overdose on prescription opioids. Uh. And then on top of that, there were three thousand and thirty six due to overdose on heroin, which of course is still an

opioid but a street drug. Yeah. And you know, even if you even if you live through it, that that tolerance and dependence and addiction are are also quite serious matter. Yeah. Of course, tolerance is a big problem with this because over time, lots of pain medications, including opioids this is where you often encounter this, become less effective. The body builds up a tolerance to them, and this means people need to continue upping their dosage. You've got to take

more to get the same effect. But then of course you're into another one of these gambling games here. Uh. It can be dangerous because the more you up the dosage, the more risk you have of side effects or major side effects up to and including death. Yeah. Tolerance is also a symptom of dependence. Lots of drugs, opioids included change the body's chemistry and functions enough that if you've been taking the drug and you suddenly stop, you'll go

through withdrawal. And and that's that's another one one of those symptoms. It means that your your body is dependent physically on that chemical and addiction, in contrast, is a mental or emotional process of mental or emotional dependence. But but it can all absolutely involve physical dependence as well. And because opioids do their job relatively well, addiction is again an unfortunately common problem. Yeah, and then of course another big problem. The stuff ain't cheap. Dealing with pain

is not a cheap proposal. Oh yeah, well, you know when when you're in chronic pain, the costs of these medications are perpetual. You know, we're we're treating the symptom more than the cause. And when you add those direct financial costs to the personal costs of being less able

to work, it can be really financially crippling. Um. The exact costs of all of these medications very really, really really widely um thanks to our you know, kind of convoluted prescription system and and our and our very complex drug manufacturing and labeling industry as well. But uh, to

give you a number, Okay. According to a survey of approximately six hundred and ninety million outpatient doctor visits made in the United States for chronic pain from the years two thousand through two thousand seven, the total cost of the pain relievers subscribed was seven teen point eight billion annually. It's it's more than two. It's it's a bunch. I wonder how much. I wonder how that compares to how

much we spent on pizza. Though I did not pull that number, I'm wishing that I had uh in the meanwhile. But it's nothing to sniff at, especially for for the individual. Oh yeah, yeah. And in addition to all of that, um and part of what we've been talking about with with the effectiveness of these drugs, we've also got the placebo effect um Because okay, so you know, pain is tricky and subjective, and the medications that treat it are

as well. And as we've said, a patient's attitude toward a pain medication can have as much impact on its effectiveness as the actual chemical pathways that are in use. So for for example, trials with placebo and with medium doses of morphine have shown that of patients will receive pain relief from the placebo and thirty six percent will

receive pain relief from the morphine. It's crazy. It's it's actually like a problem in the dug in the drug industry to get these kinds of things through testing because the rates of placebo effectiveness are so high. Uh, it's a thing that people are trying to think about. There's there's a lot of drugs that have not come to market because of that. Well, I mean, the whole issue of dealing with pain is so strange because it's not an externally verifiable You can't measure it from the outside.

You can only ask people about their perception of it. I'm trying to think what would be an external measure of pain. I guess you could like measure what people are capable of doing with certain levels of pain. But even then that's going to vary depending on their their attitude towards things and how how they feel. It's just it's a first person, subjective, internal experience and it's very real,

but there's there's no way you can look on the outside. Yeah, I'm I'm wondering if there's some way that you could. I mean, this would be be obviously way too expensive. For just an average patient doctor experience, but to measure like like neuron activity or some kind of some of the chemicals going on in the brain. But even then, I can guess that it wouldn't be the same the person from person to person. So one person's high level of neuron activity might not be enough to prevent them

from living their lives normally, whereas in another person it would. Yeah, and there's so much abuse in the industry that I think that a lot of doctors are very skeptical. I did you know anecdotally? Um, you know, like like I certainly know a number of people who have, for example, ongoing back pain problems or something who whenever they go into a new doctor, the doctor is always like, really, are you sure you crazy? Oxycode own grunt, and they're

calling them on the streets. I think. I think it's not at all. But all of this could hopefully change in the future with some of the research that people are putting into into what pain is and how to

make it better. Yeah, so it's hard to say exactly what the future of pain treatment is going to be, but we just wanted to share with you a few interesting avenues of research we've come across that that might lead to different and better ways of treating pain in the future that don't rely so much on dependence forming and endangerous opioids, or even if they do rely on them, it might help us get better use of them to treat pain better and cause fewer side effects and cost less. Sure.

And the first one, of course, because we couldn't get through a Joe and Lauren episode without mentioning some kind of creepy Crawley's has to do with tarential of venom. Yes, what can we learn from tarenttial venom? What can't we learn? Really? Yes, that that is the proper way of formulating the question. So as as you may remember, Lauren and I have talked about the potential usefulness of animal venom before and

figuring out ways to beat hard problems in medicine. I remember in one previous episode we did on that we talked about using a type of scorpion venom. I believe it was that binds to certain types of cells in the body and then allows them to be highlighted for

surgical purposes. But anyway, so studying venom or studying specifically the toxins in venom is a very fruitful avenue of medical research because though the venoms usually do unpleasant things to us, when we're trying to find ways to create targeted biomedical or biochemical changes inside the body, sort of smart bombs for the body, venoms can be a really helpful place to start because they have already been honed by nature to have a very specific effect. They do

stuff real good. Yeah uh. And by studying these specific effects, you might be able to specifically actually use the toxin in the venom to say, seek out and target a certain type of receptor in the body, or you might just be able to use it for research purposes to help you better understand what's happening at the very tiniest micro level. And so one researcher who's been studying the relationship between animal toxins and pain is the you see

San Francisco physiologist David Julius. He there was a June article in Nature called selective spider toxins reveal a role for the NAV one point one channel in mechanical pain. And what this was really about was looking at tarantula venom to better understand the what's going on in these tiny, tiny, little receptors, these molecular structures down inside our bodies when

we experience pain. And I did want to give a shout out that there is a great piece in Wired by Chelsea lou profiling Julius and this line of research, which which was a fun read if you want to look it up. But following that, so what's going on in this researcher in Julius's career? Well, so, different toxins and venom such as that of a spider may cause different types of pain, right, So some might bind with receptors that indicate mechanical pain, like a knife goes into

your skin. And I've used that example before. I guess I just can't get it out of my brain. Uh. Some might bind with receptors that do something else, like they indicate thermal pain, such as a burning sensation, or like the cap sasan in the hot chili pepper. You know that simulates a burning sensation, et cetera. And you can think about this pretty easily. You felt this difference before.

Just imagine without any stimulus, how you've probably, at some point in your stomach or somewhere in your body felt a stabbing pain and a burning pain and they're different types of sensations, and they sort of mimic this fire or knife kind of feeling. So Julius and colleagues have been studying the many different ways that these venoms on cells at the micro level to cause different types of

pain experience. For example, in a May two thousand tin article and cell Julius and and his co authors described a toxin from the venom of the earth tiger to tarantula. And you should definitely google image search that. By the way, Earth tiger tarantula straight up eight legged tigers, furry, glorious orange. It's like a cheeto came to life and was at the same time a spider and a tiger. Beautiful, fuzzy

and cute. It's great. But so they found out that the venom in this earth tiger tarantula quote selectively and irreversibly activates the cap sasan and heat sensitive channel TRPV one. And I've actually talked about that before. I remember when I was doing something with with Ben Bolan and Kristen Conger about about why spicy foods trigger burning in your mouth. All right, for the short lived but excellent food stuff.

So yeah, you have chili pepper spider fangs. Essentially, they found what this toxin does, is it props open I think those were their words, props open this channel that's usually activated by heat and by other things that simulate heats, such as hot peppers. But back to this June research in nature, So there is a tarantula called Heterosquadra maculata, and it's also known under a few odd names like the Togo starburst or the Togo starburst baboon. Oh, I'm

looking it up. It's pretty too, so many spiders for you to google. Folks at home. I hope you're having a pleasant experience now. This spider's venom uh simulates mechanical pain specifically, and that that's key because it's not like any type of pain. It's not a burning pain. It's a stabbing pain, like you would feel if something was mechanically doing damage to the tissues in your body. Lauren's

making a stabbing motion with your hands. Uh. And one of the things I was wondering here though, was should you say that the spider venoms emulates mechanical pain or should you just say it causes it? Because pain is subjective internal experience. Anyway, because it's not causing the damage, it's causing the pain, which is a separate Yeah, so I guess you can say it really does cause mechanical pain. Okay,

that makes sense. But anyway, so, cells in the nervous system rely on tiny structures called sodium channels as part of their system for communicating with one another. So you're your neurons, your your no susceptors want to tell your brain that, hey, you know something's hurting you. They rely on these sodium channels to to trade information back and forth. But the researchers noticed that this venoms toxins that zero in on one very specific type of sodium channel in

the pain receptors. There are a bunch of different types of them. So the researchers were able to figure out that these sodium channels in particular were responsible for creating the feeling of mechanical pain, the stabby pain, not the Bernie pain. So what different inst does this actually make that we learned this. Well, for instance, what if we were able to come up with pain killers that selectively target individual sodium channels, meaning that you block pain but

not all sensations. So you're anesthetic means it it doesn't hurt when they do a little local operation on you, but you don't have to go numb all day. Or what about a pain killer that doesn't even block all types of pain, Because, as we've mentioned, pain can be very useful, even life saving, when it provides a warning that there's a problem with the body. And so these avenues of research I think could potentially help get us more targeted ways of fighting pain much less of a

new kit for morebit mentality. Yeah, because that's basically what what most of our pain killing drugs these days do. Yeah, the opioids definitely are a new kit for MOREBIT. Yes, feel no pain, feel no emotional pain. Uh, lie on your couch. Probably, I really don't like opioids. They're not my friend. Uh. Genetics and gene therapy is another away from the conversation about my own personal drug uses. Alas we're talking about tar angelas. Were totally talking about tar angelas.

So yeah, you said gene therapy. Gene therapy. Yeah, So researchers are looking for and furthermore starting to identify genes that have a whole lot of different things to do with pain, like like genes that affect how much pain you feel after an injury or after a surgery. Genes that affect how your body responds to drugs, Genes that are responsible for particular conditions, like like migraines. Yeah, and I've seen that there have been some clinical trials now

using gene therapy as a possible remedy for pain. Absolutely. Other research is bent on figuring out how to interrupt the neural pathways that create that sensation of pain. Um, perhaps by messing around with the RNA of neural cells. So, yeah,

gene therapy. Other forms of therapy that are in the works are brain and or central nervous system arapies, because as we learn more about how chronic pain affects the brain and the nervous system to create those those feedback loops that we've been talking about, we might be able to gain insight into how to stop those feedback loops. Um. For for example, we're learning that immune system disorders that create inflammation in the body can cause inflammation in the

brain sometimes too, which leads to neuropathic chronic pain. Okay, so that was the pain that just comes from the nervous system, right right, and and it can and it can happen because of not damage to the nervous system per se, but damage to other parts of the body that's leading your immune system to also attack and create inflammation in the in the nervous system directly. So, so targeting the like brain specific immune cells and structures that

are participating in this could help fix it. Or hey, maybe we could learn how to replace dysfunctional nervous system cells that are encouraging neuropathic pain through something like stem

cell research. Yeah. Scientists are furthermore investigating therapies that would that would generally be termed psychological um like a like virtual reality therapy for example, but which can well, you know, it's it's the idea that with that kind of psychological therapy you can change your brain's pathways, because that's of

course what thoughts are doing. So if you are going through a targeted therapy to help change your brain's pathways, you could hypothetically change the pathways that are causing that emotional physical feedback loop that creates chronic pain. Yeah. Oh yeah, well, I mean that that is something I've definitely seen some of the people writing on this issue saying that that statement pain is in the brain. Yeah, it is. I

mean it's a mental it's a mental phenomenon. While we feel it in the part of our body that's hurting, it's relying on the central nervous system in the brain to create, certainly the feeling of pain and the reaction to the pain that makes it so distressing. And and that actually it comes back to something that I kind of would like to end on um which remember that that International Association for the Study of Pain definition. So

pain is an unpleasant sensory and emotional experience. And when you think about it, it's kind of strange because if you follow me for a second here, why is pain bad? Like why do we have a negative emotional association with it? Why is pain not just useful information? It could just be a sensation that is emotionally neutral. But you once you have this information, you're like, Okay, I need to get away from that. It could be informing you without

without making feel so unhappy. Yeah, yeah, I thought for half a second you were going to get into some weird like Clive Barker tarritory separate pleasure and pain, indivisible, infinite exactly. But but we don't really feel the So that's a question we can ask. But in practice, I know I don't. You probably don't feel at liberty to change your opinion on the positivity or negativity of pain. You know you you can't just say, you know what,

I'm gonna give intense extreme pain a chance. I'm gonna do my best to enjoy it and just not let it bother me. For some reason, it's got this access channel to our emotions that gives pain the ability to cause major problems in our lives and make us unhappy, no matter how much we would like to resolve to just ignore it or not let it bother us, you

know what I mean? Uh So, what if there were some psychological let's say, you know, you've said virtual reality, but maybe whatever the true way of getting there is. What if there were some therapy psychological or maybe more at the somatic level, but neurological treatment that managed to deactivate one half of the I s P definition without deactivating the other. Because, as we've said a couple of times now, you wouldn't want to deactivate the sensory experience

of pain. It's a partant. Yes, yes, In the words of William Shatner in that that scene from Star Trek five, the final frontier. I don't want my pain taken away. I need my pain. He's right, we do need it. It's very useful information. But what if we had some neurological procedure that would allow us to keep the pain and just take away the distressing reaction to the pain. So, in this scenario, pain becomes emotionally neutral information. It's like

a string tied around your finger. You can feel it, you can notice it's there, but it just doesn't really bother you. I don't know, I don't know. Do you think that would work. I mean, on one hand, that

seems like a preferable thing. But then on the other hand, I wonder if the emotional distress caused by pain is still just as a critic, right, So maybe maybe as a counter to my thought experiment here, what if people who are aware that they've injured themselves but it doesn't cause them distress, those people are just not very likely to seek medical attention for their injury because they don't

feel the sense of urgency created by emotional unhappiness. Yeah, that's that's an interesting question, especially considering the kind of epidemic we have about people not seeking treatment about something until it's way too late, and it's like an emergency room level kind of issue, which, of course is is driven by a lot of socionomic, socio economic factors and stuff like that. But uh, but yeah, I wonder. I wonder, like trying to think about yourself. Imagine somebody mad scientist

is offering you this procedure. You know that it actually works, but they say, okay, we will give you a give you some kind of neurological therapy that allows you to experience pain as an emotionally neutral sensory experience. I think I think that being being a relatively healthy young person, I'm I'm biased, but I don't think I would take it. Uh. And then again, like I'm not in chronic pain. I

don't have fibromyalgia. You know, I don't suffer migraines or anything like that, so I can't I I don't know. I don't know if I would want that thing. I feel like I feel like I like my emotional distress. I need my pain. Like Captain Kirk right, how about it makes us who we are? How about you? How do you feel? I don't know. I mean, I feel

both ways on this. I do I'm probably in the same boat you are actually, I mean I I could maybe cavalierly turn it down just because I am fortunate enough to personally not have severe pain to deal with. But maybe if I was somebody who had severe pain, I would take this. I don't know, Yeah, I want like I would ask the mad scientists, like, can I come back to you in like thirty years when I

will probably have a lot of arthritis. I think a lot of the decision would just come down to how much do you trust yourself to do something about pain, even if it's not nagging at you, if it's just it's just there. I'm supremely lazy. So I don't know if that's a good plan for me personally, But it's an important question and it's an interesting discussion. It's an interesting thought of of what what if that is indeed the future of pain? Well, I guess that's going to

be it for the day. But if you folks out there have come across any interesting researcher reading about the future of dealing with pain, you should send it our way. We'd like to see it. Yeah, absolutely, And also if you have any any other topics that you would like to hear us cover. We would love to hear from you. We might even get around to answering your email. We've been bad about that lately, but we're trying to get back on track. Uh. That email address is FW thinking

at how Stuff Works dot com. Of course, you can visit our website at fw thinking dot com. You can also check us out on Twitter and Facebook, where we occasionally post things. Our Twitter handle is also fw thinking, and just just search that. Just search that term on Facebook and we'll pop right up. We hope to hear from you, and one way or another, you will hear from us again very soon. For more on this topic and the future of technology, visit forward thinking dot com.

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