“Toxin” is a name that frequently reminds people of death and evil. However, tetrodotoxin (TTX), a neurotoxin more potent than the chemical weapon sarin gas and the beloved murder tool cyanide, sheds light on our fight against chronic pain.
Currently, opioids are the most common form of pain relief for cancer patients. However, a review of the effects of opioids concluded that after long term use, opioids often cause physical dependence and addiction. The review also mentioned other severe adverse responses such as immunological defects and hormonal changes. As a result, an alternative method of pain relief is needed.
Tetrodotoxin was initially discovered in pufferfish and first isolated by Japanese scientist Dr. Yoshizumi Tahara in 1909. According to C. Y. Kao’s article, people once used certain parts of the pufferfish to stop seizures and made them into tonics to boost physical and mental ability in ancient China. More recently, a Canadian Tetrodotoxin Study Group found that TTX could potentially lessen cancer pain in patients. TTX blocks sodium ion channels, a kind of protein on neurons that allows the passage of sodium ions. The influx of sodium ions creates electric signals in the brain, an important part of the body’s pain response system. As a result, if TTX can block sodium channels, it can also block pain.
According to an article by Chong Hyun Lee and Peter C. Ruben, sodium ion channels have nine varieties, which are expressed distinctively in different types of neurons. In the case of pain caused by cancer-related tissue damage, specific neurons called nociceptors are especially sensitive to the TTX. As a result, a low dosage of the toxin can achieve pain relieving effects by selectively turning off these nociceptors.
In a clinical trial conducted by the Canada Tetrodotoxin Study Group, 17 of 31 treatments resulted in clinically meaningful reductions in pain intensity, and relief of pain lasted for up to two weeks or longer. Unfortunately, this research group also showed that all patients experienced negative effects such as temporarily reduced physical sensation and tingling sensations on the skin. Nevertheless, TTX is still promising due to its lack of physical dependence compared to the widely used opioid. Moreover, TTX teaches us one thing: with modern technology and human ingenuity, a potent toxin can be converted to a remedy.
Feature Image Source: Leszek Leszczynski