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Boston Children’s researchers look to puffer fish as source of possible replacement for opioids

A puffed-up blackspotted puffer.Ocean Today/NOAA

This story could really blow up.

The puffer fish is comically ugly but tasty enough that adventurous eaters ignore the fact that parts of it are poisonous. Now, researchers at Boston Children’s Hospital are eyeing the fish’s poison as a potential new anesthetic that could one day replace opioid pain drugs with all their flaws.

Tetrodotoxin, in tiny amounts, in a slow-release formula “provided hours to days of nerve block with minimal local or systemic toxicity” in a study of rats, the researchers said in a study published Wednesday in Nature Communications.

Puffer fish, or blowfish, won their names from their ability to inflate themselves when disturbed. In Japan, where the fish are called fugu, they are cleaned and prepared by specially trained chefs, making for a thrilling, tingly dish.


Too much tetrodotoxin from a puffer fish can kill a person. But tetrodotoxin in the right amounts can relieve pain by blocking the sodium channels that conduct pain messages, the hospital said in a statement.

The researchers, led by Dr. Daniel Kohane, director of the Laboratory for Biomaterials and Drug Delivery at Boston Children’s Hospital, bound the compound to a polymer that is slowly degraded by the body through hydrolysis, the chemical breakdown of a compound by water.

“A lesson we learned is that with our previous delivery systems, the drug can leak out too quickly, leading to systemic toxicity,” Kohane said in a statement from the hospital. “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 from the poison, the researchers added a compound that made nerve tissue more permeable, allowing them to use even smaller amounts of trodotoxin.


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

The first authors of the paper were Kohane’s fellows, Chao Zhao and Andong Liu.

The researchers said that when they injected the formula near the sciatic nerve in rats, they achieved a nerve block for three days. They theorized that nerve blocks could last even longer in humans.

“The formulations developed here would likely be even safer and provide longer blocks in larger animals such as humans,” the study said.

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

The researchers noted in the study that there has been a growing interest in local and regional alternatives to opioids, which come with numerous side effects — and the risk of “tolerance, addiction, diversion, and fatal overdose.”

The researchers, together with the hospital, have applied for a patent, the hospital said.

Martin Finucane of the Globe staff can be reached at martin.finucane@globe.com