Botox could break the pain barrier

Combining the most potent neurotoxin known to man and a protein from the Mediterranean coral tree could deliver a long-lasting treatment for the chronic pain that afflicts millions of people, including cancer patients.

The neurotoxin in question is botulinum toxin, perhaps better known as Botox, the treatment that has smoothed out the wrinkles on many a celebrity forehead. But it is also used to treat an increasing range of medical conditions.

The neurotoxin, whose effects can last for months, works by blocking the release of the neurotransmitters that relay the "contract now" message from nerves to muscles. The machinery that is knocked out is actually found inside most cells, but the toxin only affects the neurons that control muscles. This is because of a targeting sequence in the toxin that only permits it to bind to muscle cells.

So Keith Foster's team at the Centre for Applied Microbiology and Research near Salisbury, UK, went looking for a targeting sequence specific to the nerves that transmit pain signals. He wanted to use this sequence to turn the neurotoxin into a painkiller. They found it in the Mediterranean coral tree, Erythrina cristagalli.

It may be a complete coincidence that the coral tree protein binds to the surface of pain neurons and no other cells, but all that matters to Foster is that it does. Since pain nerves do not carry any other sort of message, the altered toxin his team has created stops pain without affecting touch, for example.

Longer lasting
Results from tests in mice have been impressive. In three experiments, Foster's painkiller performed as well as morphine at preventing pain. But it was still working nine days later, whereas morphine would have worn off after four hours.

The team is now preparing for initial trials of the drug, Foster told the Society for General Microbiology meeting in Edinburgh, Scotland, last week. The first people to be treated are likely to be cancer sufferers or patients recovering from surgery. But with as many as one in three people suffering from some kind of chronic pain, the drug could benefit millions if it proves safe and effective.

Adding different targeting sequences could lead to all sorts of other applications, points out Hans Bigalke at Hannover University, an expert on botulinum toxin.

Inhibiting the release of inflammatory mediators might prevent asthma, for example, while disrupting glucose uptake by fat cells could stop them storing fat and so prevent obesity. "We're not short of ideas as to where we could take this," enthuses Foster.