Viper venom never switched on a single pain nerve in a new lab test, so the pain after a bite comes from tissue damage instead.

People keep their distance from snakes because they know a bite can be painful. Bites from Europe’s vipers really do hurt, so it’s easy to assume the venom is built to hurt.

Those venoms have now been tested against the nerve cells that carry pain signals, and not one of them set the cells off.

The team worked with mouse nerve cells in a dish rather than a live animal, the usual first step. They had expected the opposite.

The research was led by Bálint Üveges of the Centre for Ecological Research in Hungary and Wolfgang Wüster of Bangor University in Wales.

Colleagues at the University of Queensland ran the cell tests.

“We were surprised to find nothing in any of the venoms,” Wüster told Earth.com.

“Viper bites generally have a reputation for being painful, but it really seems that this is due to by-products of other toxic effects.”

Venom has two jobs to do

Snakes use venom mostly to catch food, and sometimes to make a predator let go.

Venom is costly to make and a gland holds only so much of it, so those two jobs pull in different directions.

Killing prey rewards toxins that shut a body down. Driving off a bird or a wild boar rewards something else: a toxin that hurts within seconds, before the animal finishes what it started.

Some prey has even evolved to resist snake venom, which pushes a hunting snake to put everything into the kill.

The researchers picked a group of snakes whose diets differ sharply.

Meadow vipers are small and eat mostly grasshoppers and crickets, prey that can’t seriously hurt a snake, though some lowland populations take vertebrates too.

The nose-horned viper, the asp viper, and the adder are larger and hunt rodents and shrews, which can do real damage to a snake’s head.

By that logic, insect eaters should be the ones with a defensive toxin.

Bee venom lit the cells up

Venom came from wild vipers in Bosnia and Herzegovina, Montenegro, Greece, Romania, Ukraine and Italy, collected between 2021 and 2023.

The snakes bit onto a film-covered tube and released the venom on their own, with no pressure on the glands.

Those venoms went onto nerve cells from mice, and onto a lab-grown line that stands in for them.

When a cell that reports pain fires, calcium rushes into it, and a dye turns that into a visible flash.

Honeybee venom was the comparison, because a bee sting is the clearest example of a venom whose whole job is to hurt. It behaved as expected, setting off 94% of the cells in one of the two tests.

In that same test, the team gave the viper venoms ten times the bee-venom dose.

No viper venom fired the nerves

Nothing happened. Not with the meadow vipers, and not with the rodent hunters. The cells responded no more than they did to plain salt solution with no venom in it, at any dose the team tried.

Composition was another matter. On a protein gel the venoms separated into clearly different patterns, and even subspecies of the adder differed from one another.

Lowland meadow vipers carried more complicated mixtures than the ones living high in the mountains.

Snake names hide that variation: the Himalayan pit viper turned out this year to be five species.

So these snakes clearly build different venoms. What none of them build is pain.

“This challenges the idea that defensive and predatory functions drive venom evolution in different directions in snakes,” said Üveges.

“Our results indicate that prey capture is the dominant force shaping venom composition in these species.”

Viper bites hurt for another reason

A viper bite still hurts. The pain just arrives by a different route.

Venom is harmful by definition, and harm hurts. Swelling, dead tissue, muscle spasm and internal bleeding all produce pain on their own, minutes to hours after the fangs go in.

That timing is the point. A toxin that hurts an hour later doesn’t do a cornered snake any good.

Hospital records agree. Patients rarely arrive soon enough for anyone to record when the pain began. In one account of a meadow viper bite, the swelling that followed hurt worse than the bite.

Asked by Earth.com what the finding changes for anyone treating a bite, Wüster kept the answer narrow.

Painkillers handle the pain. Antivenom is for the serious cases, where the job is to shut down the venom and shorten the poisoning.

Venom variety makes preparation hard

Antivenom is the harder half of that job. Snakebite kills more than 100,000 people a year and leaves hundreds of thousands injured, and the World Health Organization counts it among the world’s neglected diseases.

Antivenom is made against particular snake venoms.

The more that venom varies between species, and even between individual snakes of the same species, the less any single product covers.

That variation also makes it harder for clinics to prepare for the venomous snakes in their region.

“With so much variation in venom composition even among closely related species and within them, it is very difficult to produce an antivenom that will be effective against all the snake species or populations it is supposed to cover,” Wüster told Earth.com.

Coral snakes come next

Birds of prey and wild boar eat European vipers. Outside of spitting cobras, though, there’s almost no record of what a defensive venom does to a snake’s real predator.

A mouse cell in a dish is a rough stand-in for a hawk.

Six species and a few dozen snakes can’t rule out a pain toxin elsewhere in the group, and every sample came from one region.

Wüster named two candidates for the next round, both outside Europe.

“There are indications of specifically pain-causing toxins in some snake groups, like coral snakes and Neotropical lancehead vipers, so they would be a fertile group for further studies.”

Coral snakes could provide the clearest test yet. Pain-causing toxins appear in some species but vanish in their closest relatives.

Finding out why could reveal what actually drives venom to evolve pain as a weapon.

The full study was published in the journal Functional Ecology.

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