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Tetrodotoxin, a toxin derived from puffer fish, when used in small amounts, could relieve pain in a sustainable way
A fish toxin could replace opioids to relieve pain in the long run.
Opioids are the mainstay of the treatment of chronic and surgical pain, despite their side effects and their risk of addiction and overdose.
Conventional local anesthetics block pain very effectively, but they quickly disappear and can affect the heart and brain. A study in rats showed that tetrodotoxin, a derivative of the globally fatal fish-eye toxin, could provide long-term pain relief.
According to a study published in Nature Communications, a slow-release formulation that penetrates the nerves effectively could be a long-lasting nerve block. The study was led by Daniel Kohane, MD, PhD, director of the Laboratory of Biomaterials and Drug Distribution at Boston Children's Hospital.
Tetrodotoxin is known to have caused fugu intoxication by poorly prepared sashimi. Fish, also called a fish with a cutting head, contains the toxin in its liver, hundreds of times more toxic than cyanide
Neurotoxins in marine organisms, such as pufferfish and algae, in small amounts, can potentially provide powerful pain relief by blocking the sodium channels that carry the pain messages.
The team chose tetrodotoxin, a powerful commercially available compound derived from puffer fish. Tetrodotoxin is known to have caused fugu intoxication by poorly prepared sashimi. Fish, also called blunt-headed fish, contains the toxin in its liver, hundreds of times more toxic than cyanide.
The researchers administered intravenously a form of tetrodotoxin polymer releasing the drug at a slow and safe rate.
They also experimented with different drug fillers and polymer formulations to achieve the longest possible nerve block with as little toxicity as possible.
To further increase safety, the team combined the tetrodotoxin-polymer combination with a chemical penetration enhancer, a compound that makes nerve tissue more permeable. This allowed them to use smaller amounts of tetrodotoxin while maintaining a nerve block.
When the researchers injected the combination near the sciatic nerve in the rat, they reached a nerve block for up to three days, with minimal local or systemic toxicity and no evidence of tissue damage.
In theory, nerve blockage in humans could last even longer, since it could be administered more safely than in rats, Kohane said. The use of polymers with a longer retention time in the tissues would also prolong the effects.
"We could think of very long periods of nerve blockage in cancer patients, for example," he said. "Certainly for days and maybe weeks."
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