Pain-Killing Hunger and Superpowered Diabetic Fish

October 6, 2019

SciShow is supported by Skillshare. [INTRO ♪] Pain sucks. And if that wasn’t bad enough, the best
painkillers we have tend to be incredibly addictive and can pose
other dangers, too. So scientists are on the lookout for alternatives. And a new study in the journal Cell may have
just found an unlikely ally in the hunt: hunger. On Thursday, biologists from the University of Pennsylvania reported that mice going without food for a day felt far less inflammatory pain than their
fully-fed counterparts. The team was curious about how animal brains
prioritize competing needs. Previous research had shown that hungry mice don’t react as much to painful stimuli,
but it wasn’t clear why. So they made some mice hungry by taking away
their food for a day, while others were allowed to eat normally. Then they injected their paws with a painful
chemical, which causes both acute and inflammatory pain. Acute pain is the sharp ouch that happens
right away in response to injury, while inflammatory pain is the duller throb associated with things like swelling, and
takes a little while to kick in. It’s also one of the major causes of chronic
pain in people. Both fully-fed and starved mice noticed the
acute pain of the injection, and weren’t huge fans—they kept licking
their paws. Which suggests immediate threats to the body
take top billing in the brain. But the starved mice seemed much less bothered
over time, when they should have felt the inflammatory
pain kicking in. It was sort of like they’d been given painkillers! The next step was tracking down which neurons
in the brain were involved in the pain relief. They used a technique called optogenetics
to genetically modify cells involved in brain hunger responses so they
could be turned on with laser light. They started by activating all of these neurons, which, as expected, had the pain-killing effect. Then they went through more specific circuits
of neurons one by one, using a tiny little fiber to shine the light
on certain areas of the brain. And they found that activating just one particular
set of 300 neurons provided pain relief for the mice, without
causing the animals to eat more food. And while the results are just in mice, researchers think the same basic mechanism
probably exists in humans. And if it does, studying the neurons involved
could reveal new ways to dull long-term, chronic pain—without
forcing people to starve themselves, which is always a plus. Therapies based on this would be decades away, but given the number of people struggling
with chronic pain, this small set of neurons is an exciting find. Next, we’re continuing the theme of hunger-related
evolution, this time in little fish called Mexican tetra. Some of these tetra live in caves, and after
millions of years of living in the dark, they’ve lost their eyes. But some might argue this isn’t their most
dramatic adaptation to cave life. This week, a study in the journal Nature reveals
that these fish have all the markings of being diabetic—and
yet, they’re super healthy. It’s an evolutionary puzzle that may help
us figure out how to better treat certain metabolic diseases. Despite millions of years apart from their
river-dwelling kin, the tetra that live in caves aren’t their
own species. And each cave has separately adjusted to cavern life, which makes the species a good species to study
adaptive evolution. In this case, the researchers were looking
at how the fish survive starvation. Their caves are too dark for plants to grow
in, which makes food a rarity. So cavefish may eat only once or twice a year, when seasonal floods bring in nutrients or
when bat poop lands in the water. And to survive this starvation, previous studies
had found that compared to river fish, cavefish store more
fat when they’re fed, and lose less weight when deprived of food. To figure out how they manage to pull this
off, the team gave a jolt of sugar to three groups of independently evolved cavefish and their
river-dwelling cousins. When they checked the fishes’ blood after
8 hours, the levels of glucose in the cavefish remained
high, while the river fish’s glucose had returned
to normal. In humans, that kind of result would be a
clear indicator of insulin resistance: a reduced response to the hormone insulin, which signals cells to remove sugar from the
bloodstream. It’s one of the hallmarks of type 2 diabetes. And sure enough, when biologists injected the
animals with compounds that stimulate insulin release
or insulin itself, glucose levels only dropped in the river fish. The researchers suspect this is what allows
the cavefish to quickly put on weight and use their reserves
more slowly, which is key to surviving those long periods
between meals. But they’re not sure how the fish avoid
the downsides of being diabetic. If you’re a person, having high blood sugar and being insulin resistant is a bad thing. But the cavefish didn’t seem any worse for
wear. In fact, they seem to age more slowly than
their river counterparts. When the researchers raised the fish in tanks, they found by their middle teens, the river
fish had the telltale signs of fish aging—a hunched back, loose skin,
and raggedy fins— whereas the cavefish were still going strong. The key seems to be that the cavefish somehow
limit glycation: the binding of sugar molecules to proteins, which occurs during long periods of high blood
sugar. Glycation can change how proteins function,
damaging tissues, and it’s thought to be a major driver of
diabetes-related complications. The cavefish studied had about the same number
of glycated proteins as river fish despite their lasting elevated
sugar levels. If researchers can figure out how the fish
prevent glycation, they might be able to do the same in people
with diabetes. Like hunger-based painkillers, it would take
a while to translate the research to humans. But these little diabetic fish show that there is a way to live a long, healthy life
with high blood sugar. We just have to figure out how they do it. These amazing discoveries are also thanks
to some pretty state-of-the-art tech. And if you want to stay up to date on the
latest tech news, you’ve come to the right place. Skillshare is an online community that brings
people from all over the world together to learn
from each other. So, fittingly, they’ve asked us to help
foster community by introducing you to a new YouTube channel that you might not have checked out yet as part
of their Skillshare Spotlight program. Rene Ritchie is a long-time tech blogger and
podcaster. On his new YouTube channel, Vector, he brings
his expertise to review products and unpack current news and changes
affecting the tech world. There’s a link to his most recent video
in the description where you can learn more about Vector and
get a special offer from Skillshare. Check it out! [OUTRO ♪]

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