Tetrodotoxin, a toxin derived from pufferfish, when used in tiny amounts could give lasting pain relief
A fish toxin could replace opioids for long term pain relief.
Opioids are the mainstay of treatment for chronic and surgical pain, despite their side effects and risk for addiction and overdose.
While conventional local anesthetics block pain very effectively, they wear off quickly and can affect the heart and brain. A study in rats shows that tetrodotoxin, a derivative of otherwise lethal pufferfish toxin could provide long lasting pain relief.
A slow-release formulation that efficiently penetrates nerves, could provides long-lived nerve block, reports a study published 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.
Tetrodotoxin is notorious for causing fugu poisoning from improperly prepared sashimi. The fish, also referred to as blunt head blowfish, contains the toxin in its liver, hundreds of times more poisonous than cyanide
Neurotoxins found in marine organisms like pufferfish and algae, in small amounts, can potentially provide potent pain relief by blocking the sodium channels that conduct pain messages.
The team chose tetrodotoxin, a potent, commercially available compound derived from pufferfish. Tetrodotoxin is notorious for causing fugu poisoning from improperly prepared sashimi. The fish, also referred to as blunt head blowfish, contains the toxin in its liver, hundreds of times more poisonous than cyanide.
The researchers administered a polymer form of tetrodotoxin intravenously that released the drug at a slow, and safe rate.
They also experimented with different drug loadings and different polymer formulations to get the longest-possible nerve block with the least toxicity.
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.
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, said 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 said. “Certainly for days, and maybe for weeks.”
