Medical Science Searches for the Perfect Pain Reliever

A major challenge medical science faces is the search for more effective drugs to control pain. Neuroscientists continue to study the complex molecular mechanisms involved in the production, transmission and recognition of pain and map intricate pathways that conduct impulses to the brain where specific receptor sites are responsible for triggering pain . A drug can influence pain where it originates, along the pain pathways or the myriad of pain receptor sites in the brain.

In America, the annual cost of over the counter analgesics alone is $3 billion a year. These drugs however, do little to alleviate more severe pain that often becomes chronic and unremitting. This is the type of pain commonly experienced by the 6 million cancer patients in America and typically, adequate control of this pain requires treatment with opioids such as morphine, oxycodone and fentanyl.

Physicians are often accused of either under treating or over treating pain and they readily attest to the difficulty of providing adequate pain relief for chronic malignant pain without producing side effects in a population already receiving a plethora of potent drugs. These opioids do not always prove adequate pain relief and can act in unpredictable ways, causing unwanted side effects such as nausea, vomiting, dizziness, constipation, drowsiness and respiratory depression. There are also risks of addiction and painful withdrawal symptoms.

Puffer Fish Poison for Pain Relief?

A new approach to combat pain avoids the use of opioids completely and relies instead on a poison found in puffer fish. Tetrodotoxin (TTX), a neurotoxin present mainly in the liver and gonads of puffer fish is so powerful that a single milligram - an amount that could be placed on the head of a pin, could kill an adult. TTX modifies pain perception by blocking the sodium channel on the nerve axon, thereby preventing the propagation of nerve impulses.

The puffer fish, known as "Fugu" in Japan, has to be prepared by specially trained and licensed chefs that can separate the fish from the toxin, rendering it safe for consumption by adventurous Japanese who pay hundreds of dollars to play gastronomic Russian roulette. In Japan, fugu may be a popular dish for the well heeled, but for the emperor and his family, this is the only delicacy they are never served.

Puffer fish have fascinated observers around the world for centuries. Symbols of the fish have been identified on Egyptian tombs dated 2700 BC. The ancient Chinese and Japanese were aware of the toxin contained in puffer fish and used the non-poisonous parts of the fish as a general health tonic.

Tetrodotoxin Research

Chinese scientists have studied extensively TTX and its analgesic properties, and recent clinical trials in China have led to some remarkable findings. The intractable malignant pain of cancer patients was controlled within minutes of microgram doses of TTX and pain relief lasted 2 to 3 weeks. Another important finding was the usefulness of TTX in managing the painful withdrawal symptoms of heroin addicts. It appears that TTX acts quickly, offers a long duration of action and is safe given in very small doses. There is also no evidence of any addiction or risk of withdrawal symptoms.

International Wex Technologies, a Canadian neuro-bioscience company based in Vancouver has developed Tectinâ, a purified form of TTX now undergoing Phase II trials in Canada with test sites in hospitals in Edmonton, Montreal, Toronto, London, Saskatoon and Calgary. Each site will carefully screen and select 6 patients with cancer pain refractory to traditional pain medication.

Though the Phase II trials have not been completed, preliminary results have generated considerable interest and positive responses from the investigators involved. Dr. Edward Sellers, the chief investigator, was also responsible for the successful completion of Phase I trials where the drug was tested on 127 healthy volunteers. He states, "…small doses can have very, very powerful effects…. it's a very interesting drug and it offers probably huge potential advantages".

Another physician, Dr. Oneschuk confirms the findings that a common side effect is usually a numbness or tingling around the mouth, but otherwise deems it well tolerated. She remarks, "It is something a little different. It's quite exciting. It may be a breakthrough in pain medication". She has reported a 50% response rate, even with the use of tiny amounts of the drug. A more robust response is likely as higher doses are employed.

As we approach the final stages of these clinical trials, we may be witnessing the achievement of a major milestone in medical science, one that may forever change the quality of our lives.

Dr. Byron Law-Yone, M.D. is Medical Director, Addiction Medicine, Baylor Richardson Medical Center, Richardson, Texas. Dr. Law-Yone became a Member of the Royal College of Psychiatrists of London, England in 1971 and in 1978 became a Diplomate at the American Board of Psychiatry and Neurology. In 1988, he was certified by the American Society of Addiction Medicine and, in 1993, he obtained his certification as a Diplomat with added qualification in Addiction Psychiatry from the American Board of Psychiatry and Neurology.