Will The Lethal Pufferfish Be A Source For Chronic Pain Treatment?

Will The Lethal Pufferfish Be A Source For Chronic Pain Treatment?

A new study is investigating a possible alternative to opioids for the treatment of pain looks to use a lethal pufferfish toxin as a nerve block.

In tiny amounts, in a slow-release formulation that efficiently penetrates nerves, the toxin provided a safe, highly targeted, long-lived nerve block, researchers report in Nature Communications. The study was led by Daniel Kohane, MD, PhD, director of the Laboratory for Biomaterials and Drug Delivery at Boston Children’s Hospital.

Kohane has long researched neurotoxins found in marine organisms like pufferfish and algae. In small amounts, neurotoxins can potentially provide potent pain relief, blocking the sodium channels that carry pain messages. Kohane’s lab has experimented with various ways of packaging and delivering these compounds in tiny particles, activating local drug release with ultrasound and near-infrared light, for example.

For the new study, the team chose tetrodotoxin, a potent, commercially available compound derived from pufferfish. (Tetrodotoxin is notorious for causing fugu poisoning from improperly prepared sashimi.)

Taming a lethal toxin

Rather than load tetrodotoxin into particles as before, the team bound it chemically to a polymer “backbone.” The body very slowly degrades the bond between tetrodotoxin and the polymer via hydrolysis, the natural breaking of chemical bonds by water. This releases the drug at a slow, safe rate.

“A lesson we learned is that with our previous delivery systems, the drug can leak out too quickly, leading to systemic toxicity,” says Kohane. “In this system, we gave an amount of tetrodotoxin intravenously that would be enough to kill a rat several times over if given in the unbound state, and the animals didn’t even seem to notice it.”

To further increase safety, the team paired the tetrodotoxin-polymer combination with a chemical penetration enhancer, a compound that made the nerve tissue more permeable. This allowed them to use smaller amounts of tetrodotoxin but still achieve nerve block.

“With the enhancer, drug concentrations that are ineffective become effective, without increasing systemic toxicity,” says Kohane. “Each bit of drug you put in packs the most punch possible.”

Promising early results

When the researchers injected the combination near the sciatic nerve in rats, they achieved a nerve block for up to three days, with minimal local or systemic toxicity and no apparent sign of tissue injury.

In theory, nerve block in humans could last even longer, since one could administer it more safely than in rats, says Kohane. Using polymers with a longer retention time in tissue would also prolong effects.

“We could think about very long durations of nerve block for patients with cancer pain, for example,” he says. “Certainly for days, and maybe for weeks.”

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Bill Runge

Is this going to be another Ziconatide? Remember in the early ’90’s the toxin of marine snail was developed into Ziconatide and the medication causes sever nausea and hyperemesis and psychosis in some patients. There are so many “promising” natural remedies being researched to control pain. As a chronic pain patient myself, I am all for it but proffer caution and over-enthusiasm. This is also not another excuse for cutting off/back opioids for those whom opioids work.

A Willis

The first problem I see with this, is that it would require a nerve block every 3 days to ?? (maybe a week if they can pull it off). This is not feasible or reasonable for those with chronic pain! Secondly, I certainly wouldn’t want to be the person who tried this until it had been around for a few years (not that I would do it anyway because I’m not going to get a nerve block in my spine or elsewhere every week or less)! This might be good for those with acute pain from an injury or possibly even surgery - after it has been PROVEN to be safe!


I’m one of the unlucky chronic pain patients for which opioids do NOTHING. They simply do not work for the type of neuropathic pain I have. Anti inflammatories might, but I have had multiple episodes of inherited pulmonary embolism, so I’m on anticoagulants for life and can’t take them. I have pain 24/7/365 in my right arm/hand and no way to get any relief whatsoever. And I’ve worked in hospitals for 40+ years and seen cancer patients in horrible pain drugged out of their minds during their last weeks of life because that’s how much opioid they needed to relieve at least some of the pain. This would be a godsend for them to get pain relief and retain cognitive abilities so they can at least communicate with family in their final days. Please don’t discount something that might benefit someone else just because you don’t want it.


Nerve block have never worked for me and I’ve had over 30 - most only bc if I dont get them I cant get my pain meds. Ridiculous scam that’s not even fda approved.

A group at the University of Texas at Austin did some pioneering research on sodium ion channels, that began with one question. “Why doesn’t puffer fish poison kill the puffer fish?”

The answer proved surprising: the cells surrounding the poison gland of the.puffer fish have no nerves. And the poison sac of the fish has mutant sodium ion channels that are extremely slow to recharge the nerves and muscles, for a second squirt of poison.

It turns out that if Twp puffer fish get in a fight with each other, they can both die by injecting each other with the poison. All their other nerve and muscle cells are normal!

This story points up the value of doing basic science research. A friend who worked on the puffer fish study in Austin and now teaches biochemistry in New Mexico, swears that her biggest problem is with religionists who oppose all medical research, fearing the research might prove that evolution took place. It’s not hard to see how scientists cling to scare stories like the Opioid Hysteria, when advertising what they study. Without a crisis, the anti-evolution crowd attack scientists for doing science.

Can this polymer trick by Dr Kohane make cancer surgery safer? Chemotheay nowadays means soaking the body in poisons that kill cancer a little faster than normal cells. If Dr Kohane’a polymer can safely deliver a poison that’s 1200 times stronger than cuanide, could a surgeon smear a gel of that polymer, bonded to a stiff dose of a chemotherapy drug, into the margins of where he cut out a tumor? That would make chemo a great deal safer and stop some.cancers from recurring!


I was scared of Botox, now they want to use a different, even scarier nerve block?
Whoops! it becomes permanent and then what? Oh well. at least somebody ELSE is making the $$$.
That’s all they can think of in pain relief is destroying our nervous systems now.

Meanwhile, cut ’em off their pain meds which are working somewhat and watch them squirm call us addicts and get rid of some of the useless eaters.

And no to Allen, the first comment. My doc couldn’t give a flying one for what this is doing to my precarious health.

The ONLY reason I’m considering staying alive is to do my part to vote out this most corrupt/cruel administration of my lifetime…if I can last that long.
Life sucks right now

Absolutely spot-on Robert. Absolutely agree with Alan and patient advocate. We as pain patients can’t get on coverage constant news about our condition and suffering but they’re all about the love the television companies AMC, Sundance and the others BC all I see anymore are advertisements about LBGQ community. This is such a small number like 9% of the world how is it that they can get their agenda out and have major television companies backing them and advertising for them but we are denied at the doctor’s office, CDC. I don’t care how they live their life style but it’s just ridiculous that the comparison of numbers and the backing that they’re getting when 50 million intractable pain people can’t be heard. Every movie has some gay couple in it why isn’t there any movies other than Roseanne about people living with chronic pain. Where is our coverage? Where is the love for us? Where’s our rainbow?


Is this becoming a promotion site for alternative treatment? I thought we were working to keep opioids for those of us that have been successfully treated long term. That is our God and Constitutional right. Testimonials on our medical conditions won’t change the unethical withholding of drugs. 15 years now with spinal nerve damage, autoimmune disease, both knees and ankles permanently damaged (and all service connected) doesn’t matter. It is our RIGHT to choose our treatment and that right should be defended. Research and alternatives are MONEY MAKERS when in fact we have the drugs that work when used safely. The Doctors that agree are persecuted. Lets all just drink ourselves to death and smoke as many cigarettes as possible!


NO THANKYOU!!!! I am so sick and tired of this garbage…we’re being taken to the slaughterhouse person by person, this is by far, more lethal than 5 mg’s of oxycodone 6 times a day, I’m 75, take my meds responsibly, there is no “high”, just enough relief to feel somewhat human for a few hours, and they want to stuff lethal toxins into me….go to h-l, just like they are trying to condemn us to.

Hayden Hamby Jr.

I have already been made aware ( without detail) of a new “pain medication” that will work , or “may” work for some pain management patents. I was told to just hold on, and wait for the new “pain management medication”. HOLD ON?? Hold on to what? Pain fog, continuous no sleep pain endurance!. By the way, I was informed that insurance companies may or may not pay for the “new medication”. It will cost unreal money thus more profit for individuals with stakes in pharma.


I dont think I’m ready to experiment with deadly toxins for chronic pain. My rule is that if any drug hasn’t been on the market for 20 yrs, i dont take it! And if a new drug is offered that has been on tje market for 20yrs, I’m still going to check it out and make a decision. Drug responsibility starts with tje patient because MD’S only get 1 semester of pharmaceuticals. They’ve got drug companies coming in every day to bring samples. Samples mean new drugs and the patient is the first in line to be part of a drug trial. Do you want to be a human lab rat?


I agree with Lauren. I may consider it after it’s been tested on a couple thousand people first and see what the side effects are and if it works!. I’ve been a Guinea pig too many times! I’m older and wiser now and I learned years ago I must look out for myself and I do not have to do anything I don’t want to do!

Thomas Wayne Kidd

One more tool in the killing off of pain patients. Doesn’t anyone realize that this is just more Antichrist stuff. We have a herbal medicine from the Poppy plant which works. Damn these [edit] and their poisons. Just another fake, false hope to the gullible.

Thomas Wayne Kidd

Yeah, Yeah, a few years ago snake venom was touted as a new pain killer but suddenly poof, nothing.


Using the Pufferfish’s toxic substance to eliminate nerve pain would be wonderful. And it would get the government off the doctor & patients backs! Please let’s hope this can work for all of us in pain.

Lauren Gilbert

Sounds interesting. I think I’d like to hear more about it after they’ve tested it on a couple of thousand human beings with no adverse effects. Tetrodotoxin is scary stuff. I’ve been on opioids for the last 14 years and I can say 2 things about them; they don’t get me high all they do is Target the pain center in my brain there for lessening my pain but leaving me at a 7 on the pain scale which I can deal with + 2 I’ve never become paralyzed or not felt anything in all those years. Oh I guess I could say a third thing I am not an addict, I take my medication as prescribed, even now since I have been cut to less than half of my normal dosage.

But again the Tetrodotoxin thing sounds promising oh, I just want to hear more about it after they’ve tested it on thousand or 2,000 brave human beings.

Gary Priebe

I’m NOT on board with the Poisonous Puffer Fish injected into my spine especially when I know the Fentanyl Patch does wonders for me. Leave me alone thank you very much. I don’t abuse my medication I take it as directed and it helps me immensely. I was doing FINE until I was forcefully made to see Travis Lee at Kure? Pain Clinics who then tapered me so much that now I am miserable and going to the ER a lot which Medicare is paying stupid amounts of money for. Its ridiculous…thanks Travis!! I won’t even refer to him as a Doctor because a Doctor has compassion for and HELPS their patients that was NOT my experience at Kure? Pain Clinic.


We are now on the precipice of total insanity in the prohibition of opioid pain medication. Now here comes a new alternative to making Dr. Kolodny an alternative fortune by Botoxic-ing our CNS.

Tetrodotoxin is a sodium channel blocker that is up to 1,200 times more poisonous than cyanide. There is enough toxin in one pufferfish to kill 30 adult humans for which there is no known antidote. This of course is safer than a 5mg. Oxycodone pill?

Is it just me, or has the world become unrecognizable?

Patient advocate

Yes let’s add more toxins to our body. For those who have autoimmune diseases, and spinal cord injuries/diseases leaves patients with excess toxicity already due to the immune system being compromised.
This study like many when it comes to medications always leaves out the most important variable. There is no one size fits all, and every patient metabolizes medication differently. For those patients who are slow or poor metabolizer, this could possibly be deadly due to the medication not metabolizing normally.
I do not understand how this issue is left out of every study I’ve reviewed when it comes to treating pain!
More importantly, would this medication ever be considered for injections near the spine?

Alan Thurman

new pain relief medication puffer fish and cane cone snails. let me be the first to say, no thank you. although i’m not opposed to anyone trying anything the want to try, it’s your body and you are responsible for your body, not the fda or dea or any other government agency. enough is enough! i’m blown away by the ignorance surrounding g pain killers. what a mess. how to screw poor people 101. take away their ability to work(check). turn medication that works into the devil(check) ruin the doctor patient relationship ( does any feel like their doctor is more concerned about other issues instead of the main issue helping you heal). i feel making me heel is about the fourth consideration of the patient doctor relationships in 2019. those people on medicaid and use pain killers will not magically have their pain stopped s d go back to work because they had their medication taken away. i have no idea how to approach a doctor. i gave no idea how to get better. iI have fain d 75 pounds in the last two years after my pain meds were taken away. the opioid policy is killing me and bankrupting me into a bigger on s street corner. YOUR KILLING ME!