The Future of Pain

Pain is both a physical and emotional experience, which makes it hard to treat. Today's therapies (like opioid drugs) come with dangerous side effects. How could new research change the ways we treat pain?

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Episode Transcript

Speaker 1 (00:00):
Brought to you by Toyota. Let's go places. Welcome to
Forward Thinking. Hey, and welcome to Forward Thinking, the podcast
that looks at the future and says, I guess I'm
always hoping that you'll end this rain. I'm Joe McCormick

(00:21):
and I'm Lauren Bob and our regular host Jonathan Strickland
is not with us today. He's I think it a
castle in Wales playing quidditch or something something to that extent. Yes,
uh so, you know, go Thunderbucks. And in his absence,
we are going to to talk about a kind of
a kind of upsetting subject today. It's great, but it's universal.

(00:43):
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

(01:04):
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

(01:26):
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

(01:51):
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.

(02:12):
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

(02:34):
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,

(02:55):
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.

(03:15):
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,

(03:37):
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

(03:59):
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,

(04:20):
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

(04:42):
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,

(05:03):
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

(05:26):
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

(05:49):
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

(06:11):
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

(06:31):
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,

(06:55):
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,

(07:16):
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

(07:38):
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,

(08:04):
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.

(08:27):
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.

(08:51):
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.

(09:14):
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

(09:34):
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

(09:56):
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

(10:16):
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

(10:37):
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

(10:58):
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.

(11:20):
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,

(11:43):
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

(12:05):
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

(12:25):
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

(12:46):
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

(13:09):
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

(13:32):
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

(13:54):
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

(14:18):
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

(14:39):
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

(15:00):
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

(15:22):
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

(15:43):
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,

(16:04):
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,

(16:30):
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

(16:50):
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

(17:12):
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

(17:36):
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

(17:58):
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.

(18:18):
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

(18:39):
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

(19:02):
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.

(19:23):
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

(19:45):
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

(20:07):
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

(20:29):
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.

(20:52):
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

(21:15):
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

(21:37):
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

(22:00):
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

(22:22):
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,

(22:44):
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

(23:05):
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

(23:26):
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.

(23:46):
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

(24:09):
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

(24:31):
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

(24:51):
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

(25:11):
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

(25:32):
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

(25:54):
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

(26:15):
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

(26:36):
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

(26:57):
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

(27:18):
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

(27:41):
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.

(28:03):
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,

(28:24):
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.

(28:47):
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

(29:08):
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.

(29:31):
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,

(29:56):
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,

(30:17):
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

(30:39):
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

(31:03):
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

(31:25):
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

(31:46):
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

(32:08):
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

(32:29):
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

(32:50):
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

(33:14):
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

(33:34):
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,

(33:54):
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

(34:16):
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.

(34:37):
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

(35:00):
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.

(35:22):
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.

(35:43):
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

(36:04):
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

(36:28):
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

(36:52):
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,

(37:15):
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.

(37:37):
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

(38:01):
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

(38:22):
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

(38:45):
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

(39:07):
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

(39:31):
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,

(39:53):
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.

(40:14):
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

(40:36):
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

(40:57):
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

(41:19):
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

(41:40):
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

(42:02):
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?

(42:25):
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,

(42:50):
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

(43:11):
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

(43:32):
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

(43:52):
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

(44:16):
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

(44:37):
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

(44:58):
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

(45:18):
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

(45:39):
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

(46:00):
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

(46:21):
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

(46:42):
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

(47:08):
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

(47:29):
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

(47:50):
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

(48:11):
and the future of technology, visit forward thinking dot com.
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