Pain relief from under the sea
The puffer fish is widely known as a delicacy that can kill. Valued for its bittersweet taste, the fish contains a toxin in its liver and gonads that is fatal to humans within four to six hours of consumption.
One person’s poison may be another’s cure.
Researchers are testing a derivative of the puffer fish toxin as a novel way to block pain. In a small study published last month in the Journal of Supportive Oncology, the substance, called tetrodotoxin, was found to reduce cancer pain by at least one-third in 68% of patients.
“These patients had already tried the best therapies available and were not getting pain relief or were having side effects that affected their quality of life,” says Dr. Edward Sellars, the principal investigator of the study. “With tetrodotoxin, in some patients the decrease in pain lasted well over a week.”
If the drug proves as effective as it seems, it would be the first in a new class of pain medications -- and would be free of the side effects associated with narcotics.
People with severe pain need additional options, says Mary Pat Aardrup, executive director of the National Pain Foundation. Existing drugs often cause side effects such as drowsiness, nausea, constipation, slower breathing and the risk of dependency.
Although better training of doctors could improve pain management for many patients, new medications also are needed, Aardrup says.
“Pain is a new and emerging field,” she says. “It’s still in its adolescence. There is so much to be learned on all fronts. That’s why the research end of it is so critical.”
Unlike morphine and other opioids from which narcotics are made, tetrodotoxin is not addictive, Sellars says. The injectable drug, called a sodium channel blocker, intercepts the electrical signals carried from nerve to nerve by a specific kind of sodium channel. It prevents the transmission of pain signals by deadening pain at its source.
The medication may prove most useful on neuropathic pain, such as chronic back pain and shingles pain, which is severe, chronic and difficult to treat.
“With this kind of pain, the nerves have been working overtime for so long that the nerves themselves have changed and spontaneously send pain signals,” says Sellars, president of Ventana Clinical Research Corp. in Toronto. “This drug may help.”
In early studies, tetrodotoxin (the brand name is Tectin) produced no serious side effects. About 5% to 10% of patients developed mild nausea, and all patients experienced numbness around their lips for about 30 minutes following injection of the toxin. Researchers aren’t sure what causes the numbness but suspect it’s linked to the fact that a fine network of nerves runs through the lips, Sellars says.
Dangerous though the puffer fish toxin may be -- it’s 10,000 times more deadly than cyanide -- it has some history as a medicine. During World War II, Japanese doctors used it to treat migraines. More recently, heroin addicts have taken it to help combat withdrawal symptoms. Researchers say the toxin could be used to treat a broad range of pain conditions.
International Wex Technologies, the Vancouver, Canada-based maker of tetrodotoxin, uses only two species among the 150 kinds of puffer fish (also called fugu or blowfish) and is testing a dose so tiny that one fish can produce 660 treatments.
“The initial trials have been in people who were very sick and in great need of new analgesics,” Sellars says. “But the side-effect profile of this drug suggests that it may be effective in a wide range of conditions.”
The next study on the substance will include about 150 patients with pain caused by various types of cancer at 25 centers in Canada. (The company has plans to initiate a similar study in the United States this year.) The study will be a randomized, controlled trial, meaning that some patients will receive tetrodotoxin injections and the others will receive a placebo.
Both groups will continue to receive other types of pain medication as needed.
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Easing two kinds of suffering
How pain is treated depends somewhat on its type.
Neuropathic pain: Described as burning, shooting or electric-like, this type of pain is caused by damage to the peripheral or central nervous system. Neuralgias, diseases of the spinal cord and some types of back pain are examples of neuropathic pain. It can be difficult to treat, often requiring opioids.
Nociceptive pain: Dull, throbbing and achy (though occasionally sharp), this type of pain is caused by stimulation of the nerve fibers in tissue, bone, muscle or vessels. Bone pain, injury pain, pressure pain and cancer pain are examples of nociceptive pain. It’s usually easier to treat than neuropathic pain, and doctors typically recommend milder pain medications, such as anti-inflammatory agents. Stronger medications may be needed for severe pain.
