Sea Snail Toxin Offers Promise For Pain

Khyber writes to tell us about research out of Australia that holds out hope for chronic pain sufferers. The toxin of a sea snail, called conotoxin, has a component that has been shown to directly target pain receptors in experimental animals. Unlike essentially all existing pain relievers, conotoxin seems to suppress pain without side effects. Human trials are a year away.

Comments

Toxin...Toxic?

[jellomizer]

Isn't a Toxin Toxic to people. Or is it just Toxic to the Snail?

Re:Toxin...Toxic?

[Tyler Eaves]

It's all in the dosage. *ANYTHING* (even, say oxygen or water) is toxic if given in a high enough dose.

Re:Toxin...Toxic?

[smallfries]

Isn't a Toxin Toxic to people. Or is it just Toxic to the Snail? Another way to look at it is read what the submitter really meant. You often have
to translate slashdot stories. "Unlike essentially all existing pain relievers,
conotoxin seems to suppress pain without side effects." really means "Like all
existing drugs that haven't been through large scale trials, conotoxin appears
to be free from side-effects. The toxicity is probably dependent on the dose, the
patient, the length of usage and about a million other (currently) unknown
factors.

Re:Toxin...Toxic?

[MrLogic17]

Yes, but not the reason you think.

http://en.wikipedia.org/wiki/Nehushtan
Numbers 21:4-9

(Pardon the King James, couldn't find a modern transation in short order)

21.6. And the Lord sent fiery serpents among the people, and they bit the people; and much people of Israel died. 7. Therefore the people came to Moses, and said, We have sinned, for we have spoken against the Lord, and against thee; pray unto the Lord, that he take away the serpents from us. And Moses prayed for the people. 8. And the Lord said unto Moses, Make thee a fiery serpent, and set it upon a pole: and it shall come to pass, that every one that is bitten, when he looketh upon it, shall live. 9. And Moses made a serpent of brass, and put it upon a pole, and it came to pass, that if a serpent had bitten any man, when he beheld the serpent of brass, he lived.

Re:Toxin...Toxic?

[torako]

While your Bible citation applies too, most people would say that the Rod of Asclepius is a symbol of Greek mythology (probably older than your Bible text) Wikipedia text: http://en.wikipedia.org/wiki/Rod_of_Asclepius The summary says:

The Rod of Asclepius is an ancient Greek symbol associated with astrology and healing the sick with medicine. It consists of a serpent entwined around a staff. Asclepius, the son of Apollo, was practitioner of medicine in ancient Greek mythology. He was instructed in medicine by the centaur Chiron also connected to the constellation Ophiuchus.

Re:Toxin...Toxic?

[Anonymous Coward]

Large dosages of water have been found to cause swimming in laboratory animals.

(from USENET circa 1985)

Re:Toxin...Toxic?

[HolyCrapSCOsux]

Proves the power of prayer when combined with the power of a magic stick.

Re:Toxin...Toxic?

[Hatta]

It's all in the dosage. *ANYTHING* (even, say oxygen or water) is toxic if given in a high enough dose.

Including ethanol, nicotine and caffeine to name a few.

With the notable exception of THC, the active ingredient in marijuana. There has never been a single fatal case of THC poisoning in all of medical history.

Re:Toxin...Toxic?

[TranscendentalAnarch]

Actually, it is.  It contains Caffeine, Theobromine, and other chemicals, that with the correct dose can kill you.  Theobromine is actually responsible for the death of dogs and cats that have consumed too much chocolate.  http://en.wikipedia.org/wiki/Theobromine

Misleading title

[Rosco P. Coltrane]

Shouldn't it read "Sea Snail Toxin Offers Promise For Pain SUFFERERS"? At first I thought it was an article about some new clever torture method for Gitmo prisoners or something...

Re:Misleading title

[pilgrim23]

Human trials are still a year away? I see the research is progressing at a snail's pace...

Re:Misleading title

[sublimusasterisk]

True, but given it's a sea snail, I'd say it's coming along swimmingly.

Bitter Irony

[susano_otter]

In before "we must halt all industrial and technological advancements, to stop global warming before we lose all these wonderful natural cures!"

The bitter irony is that it's these very industrial and technological advancements that make the discovery, analysis, synthesis, mass production, and world-wide distribution at affordable prices of this painkiller possible in the first place.

It's depressing how many people demand the benefits of civilization, without accepting any of its tradeoffs.

Re:Bitter Irony

[Chris Burke]

I don't think there are actually that many people who say "we must halt all technological development".

That's usually the hyperbolic strawman of the anti-conservationist who extrapolates spending money on better alternatives to current tech and trying to use less of what we do now (e.g. drive more fuel efficient cars) into some crazy luddite back-to-nature wildlife.

Personally I think that point of view is retarded. I'm a conservationist and environmentalist because I like the benefits of civilization, and I would like for myself and as many generations of descendents as possible to be able to keep them.

One of the tradeoffs of civilization is figuring out how to make it sustainable. Our current method is not sustainable. Refusing to change because you want to keep your lifestyle is to guarantee that you lose that lifestyle.

Anyway, I think slug-slime pain killers are awesome.

Re:Bitter Irony

[rednip]

The bitter irony is that it's these very industrial and technological advancements that make the discovery, analysis, synthesis, mass production, and world-wide distribution at affordable prices of this painkiller possible in the first place.

So, you think global warming is an advancement. Personally I see it as an accounting issue; hidden costs which some people pass on to other people, in particular future generations. Perhaps the reason why the Northeast is considered so 'liberal' is that one doesn't have to go far to find a brown field. A place of dead earth, unfit for human development, left by some long gone business which was unburdened by environmental regulation. The cleanup of someone else's mess is a continuing burden, both on the treasury, and the health of people who have long ago, if ever, benefited from their creation.

At one point cities didn't have sewers or trash collection, they just threw their daily waste into the middle of the street. Often the contents of chamber pots would rain down on the pedestrians below, and the rivers became so choked with human and animal filth, that they caused plague, and misery. Eventually cities, and towns raised taxes for sewers, required trash collection, then sanitary sewers, and eventually waste treatment facilities. Today one doesn't think of these things as unnecessary, or too costly, as the benefits of these requirements obviously far outweigh the costs of not having them, yet when the laws were first developed buffoons such as yourself, fought their implementation as being too costly, and unneeded. History has proven those fools wrong, as it will you.

Re:Bitter Irony

[susano_otter]

Here's the thing, though: Life itself demands a lifetime of servitude.

And the work I do now, to keep body and soul together, not only is it easier than the work I would've had to do without civilization, but my quality of life is better, the scope of leisure activities available to me is greater, and the surplus wealth I have accumulated is greater, than anything our primitive cave-dwelling ancestors ever enjoyed. And that's with The Man exploiting me every day.

What does your post-apocalyptic Rockefeller Center have to offer me, that's superior to civilization? And if the uncivilized wilderness really has that much to offer, why are you here fondling the Internet, instead of stalking beasts in the Amazon the way Mother Nature intended?

Ouch.

[Das Auge]

Death, the ultimate pain release...and it's good for weight loss, too.

Experimental animals?

[jonnythan]

"The toxin of a sea snail, called conotoxin, has a component that has been shown to directly target pain receptors in experimental animals." ..... What about regular animals?

Is that the next step?

Experimental animals -> regular animals -> experimental humans -> regular humans??

Wow..

[FunWithKnives]

This could be great for people like me. I suffered a lower-lumbar spinal fracture almost seven months ago. The doctors tell me that, essentially, I have to deal with chronic neck and lower back pain for the rest of my life. I take opiate-based pain medicine twice a day for it. The stuff wigs me out sometimes, though, and I slog through the day in somewhat of a fog. Not good for a college student. Hopefully this will make it to the market, and I can finally get some pain relief without getting "high".

Before anyone else chimes in..

[Khyber]

It's not the toxin itself, rather a component of the toxin that offers the pain relief. The /. editors must've edited that out, from my original entry.

Elan already has a Conotixin on the market

[Anonymous Coward]

Irish biotechnology company Elan Pharmaceuticals markets the first commercial conotoxin analgesic, ziconotide (Prialt), for intractable nerve pain. It is from the omega-conotoxin family, one of five major families of conotoxins.

http://www.theage.com.au/news/creative--media/pain killer-comes-out-of-its-shell/2005/07/24/112214372 8598.html

Links to university release & the article in P

[PrebleNY]

here is the press brief from the university's website, includes a picture of Dr Ekberg
http://www.uq.edu.au/news/index.html?article=11048

and if you have the chops to read the study, here is a link to the abstract
http://www.pnas.org/cgi/content/abstract/103/45/17 030

looks like the full text is free (unless my institution's IP range has a subscriptionn and it would otherwise be locked down)

Different from ziconotide?

[Wilson_6500]

There's already an anesthetic drug out there that's based off of a conotoxin. Ziconotide, from what I can tell, is a synthetic conotoxin substance based upon omega-conotoxin derived from the cone snail. Wikipedia has an entry on it, including that it's already in use as the drug "Prialt."

I don't understand why nothing in the article even mentions this already-existing drug derived from (probably different) conotoxins.

At least one conotoxin already commercialized.

[Vellmont]

A brief look at Wikipedia indicates there's already a commercially available drug derived from conotoxin that provides relief from pain:

-conotoxin inhibits N-type voltage-dependent calcium channels. Because N-type voltage-dependent calcium channels are related to algesia (sensitivity to pain) in the nervous system, -conotoxin has an analgesic effect: the effect of -conotoxin M VII A is 100 to 1000 times that of morphine. Therefore -conotoxin M VII A is used as an analgesic drug named ziconotide; it is marketed under the brand name Prialt®.

Presumably this is a different component of conotoxin.

Re:At least one conotoxin already commercialized.

[alkaloids]

Right. The article is horrendously vague, though I guess it has to be. "Conotoxin" is the name of actually a family of different compounds (small peptides) that tend to interact with ion channels. Ion channels are the proteins in neurons that basically transmit electrical information from one end of a neuron to the other. So if you can clog up ion channels, you can stop information transfer - including pain information. There are lots of ion channel types, and lots of different ion channel blockers and it's long been one of the promises of understanding ion channels that if we can block specific ones with high potency and specificity we'll be able to stop pain. The hope is that you'd be able to block the channels involved in transmitting information about pain, but not interfere with the channels that transmit signals from the brain to the muscles. This is all similar to how drugs like lidocaine work where they will 'break' an ion channel for awhile and so you can't feel pain from those neurons. However, this is different from other pain treatments which function by changing your perception of pain (things like morphine or other opiates).

So anyway, that's why toxins can be used to treat pain. The earlier drugs developed were (omega)-conotoxins, which tend to target the voltage-dependent calcium channels. This is from the (mu-O)-conotoxins which is a different family that tends to block the voltage-gated sodium channel, which is actually the channel I've done most of my PhD research on. In fact, I was in the process of writing a research proposal to do pretty much what the experimenters in this study have done. It looks really interesting, but there are still tons of problems involved in using peptides therapeutically (your digestive system tends to be remarkably good at tearing peptides to bits, for example). Oh well, you can't win 'em all.

Re:At least one conotoxin already commercialized.

[StikyPad]

Prialt has a few caveats.

Be nice if they could find something better than morphine though. I've been on drips twice in my life. (Yeah, I guess I'm accident prone.) Anyway, 1) it's not so much pain relief as much as "I'm so euphoric that I don't care that my arm hurts like a bitch," especially for something like getting a wound scrubbed out with a Brillo pad, 2) the side effects suck and 3) coming down is like the worst hangover you've ever had, only worse. Even thinking about it right now makes me nauseous.

Cone Snail Venom

[eli pabst]

I recently saw a very cool lecture by Baldomero Olivera, one of the people who discovered these compounds in cone snail venom. Apparently back in the day, they were trying to find the compound in cone snail toxin because it was terribly toxic and a lot of people in the Phillipines died from stepping on snails. So they took some cone snail toxin, fractionated it and then injected individual fractions into mice, expecting to see a single fraction that contained the "toxin" compound of interest. Instead, when they did the experiment they found that a large number of fractions had all kinds of crazy effects on the mice, including behavioral and motor effects. What they discovered was that there are a large number of compounds that make up the cone snail venom, each had a slightly different role in capturing prey. Some worked as short term paralysis agents that allowed the snail to capture its prey while others worked long term and allowed the snail to slowly eat its prey whole. There were also some that had overlapping function, but appeared to work better against different types of prey. Very cool talk considering it was about Cone Snails.

How Soon Before...

[SRA8]

How Soon Before...my kids in high school start sniffing this stuff? Damn kids these days...

Re:This should come in handy for anyone that

[AndersOSU]

Yeah but morphine, heroine, cocaine, and many, many other drugs have promised pain relief without any side effects. I'm not a doctor, but I'd be surprised if there were ever a drug that didn't have any side effects.

People are complex intertwined systems, you can almost never change something without unintentionally changing something else.

Re:As usual. . .

[SydShamino]

And the guy several posts above who broke his back and has been told by his doctor that he will suffer from chronic pain for the rest of his life? Should we not research medications to ease his pain, so he can better figure out why his back hurts? (Hint: It hurts because he broke it.)

Just because your chronic pain is self-induced, it doesn't mean all people's pain is so caused.

Cone shells

[kbahey]

These things are very pretty and very deadly as well.

The proper name for them is not "sea snails" (there are lots of snails in the sea). The are called cone shells or cone snails. See the Wikipedia article on them.

I used to see them when snorkeling in the Red Sea. They are one of the few snails that are "clean" since they have a mantle withdrawn over the shell and hence algae and barnacles do not attach to it. The other snail that does that is the cowrie shell. If you find a dirty shell, then it is because the animal inside it has died, and the algae has move on it.

The cone shells are very very toxic and as far as I recall have no antidote. They have a harpoon like needle that injects venom, and a proboscis to swallow prey with.

One true horror story from Sinai in Egypt was about a woman tourist who was found dead under the water after scuba diving. They took the body out and checked the regulator, the air supply, ...etc and all was good. When they unzipped the wet suit, a live cone shell fell off. What seemed to have happened is that she saw this pretty shell and did not know it was toxic. She just decided to keep it safe and unzipped the suit and tucked it in.

Scientific American

[rrohbeck]

Scientific American had it too: http://www.sciam.com/article.cfm?chanID=sa006&colI D=1&articleID=000D45AD-46FB-1237-81CB83414B7FFE9F

April 2005 issue

INNOVATION
A Toxin against Pain
For years, scientists have promised a new wave of drugs derived from sea life. A recently approved analgesic that is a synthetic version of a snail toxin has become one of the first marine pharmaceuticals

Pain medication

[XNormal]

Aspirin, ibuprofen (Advil), etc are anti-inflammatory drugs. They block the body's response to provocations which is often what causes most of the pain. They all have the unfortunate side effect of irritating the stomach lining and increasing the chances of getting an ulcer. Nobody really knows how many (mostly elderly) people die from internal bleeding caused by these drugs every year.

Opiates affect the way the brain perceives pain. They work great and are relatively safe - but addictive. Some people find them pleasurable but most people don't really enjoy the experience. Both groups can become addicted if they use them often enough. The first group is simply more likely to do so for non-medical reasons.

Nobody is really sure how acetaminophen (Tylenol) actually works. It appears to be a variant on anti-inflammatory drugs with fewer side effects but it may also have some direct effect on the brain. It's safe and effective for minor pains but its usefulness is limited for severe pain because larger doses are toxic to the liver. This one also kills many people every year who don't take the warnings seriously. Many of the victims are children.

A new drug that affects the pain receptors directly could be a welcome addition to this arsenal.