By Pat Anson, Editor
An experimental study on genetically modified mice may have uncovered a way to make low doses of opioids more effective in treating chronic pain.
Researchers at University College London are studying “transgenic” mice that were modified to carry a genetic mutation from humans who are unable to feel pain. The humans have a defect in their nervous system that prevents them from sending pain signals through a sodium channel known as Nav1.7. People born without working Nav1.7 can still feel touch normally, but not pain.
The researchers found that that mice who lack Nav1.7 produce higher than normal levels of naturally-produced opioids. Transgenic mice have twice the levels of natural opioids as unmodified mice from the same litter.
To block the effects of the natural opioids, the researchers gave the mice naloxone, an opioid blocker used in addiction treatment, and found that they became able to feel pain.
They also gave naloxone to a 39-year-old woman with the same rare mutation and she felt pain for the first time in her life.
"Studying the mice showed us what was going on in the nervous system that led to painlessness and our findings were directly translatable to humans, as confirmed by the painless patient,” said senior author Professor John Wood, University College London.
"The secret ingredient turned out to be good old-fashioned opioid peptides, and we have now filed a patent for combining low dose opioids with Nav1.7 blockers. This should replicate the painlessness experienced by people with rare mutations, and we have already successfully tested this approach in unmodified mice."
Broad-spectrum sodium channel blockers are already used as local analgesics, but they are not suitable for long-term pain management because they cause complete numbness and can have serious side-effects over time.
Opioid painkillers such as morphine are effective at reducing pain, but long-term use can lead to dependence and tolerance. As the body becomes used to opioids, they become less effective and higher doses are needed. Side effects also become more severe.
"Used in combination with Nav1.7 blockers, the dose of opioid needed to prevent pain is very low," explains Wood. "People with non-functioning Nav1.7 produce low levels of opioids throughout their lives without developing tolerance or experiencing unpleasant side-effects. We hope to see our approach tested in human trials by 2017 and we can then start looking into drug combinations to help the millions of chronic pain patients around the world."
Wood’s study is being published in the journal Nature Communications. Wood has filed for an international patent on his discovery.