Quirky Science
SECRET TO PAINLESS LIFE
People born with a rare genetic mutation are unable to feel pain, but previous attempts to recreate this effect with drugs have had surprisingly little success. Using mice modified to carry the same mutation, UCL researchers funded by the MRC and Wellcome Trust have now discovered the recipe for painlessness.
'Channels' that allow messages to pass along nerve cell membranes are vital for electrical signalling in the nervous system. In 2006, it was shown that sodium channel Nav1.7 is particularly important for signalling in pain pathways and people born with non-functioning Nav1.7 do not feel pain. Drugs that block Nav1.7 have since been developed but they had disappointingly weak effects.
The new study, published in Nature Communications, reveals that mice and people who lack Nav1.7 also produce higher than normal levels of natural opioid peptides.
To examine if opioids were important for painlessness, the researchers gave naloxone, an opioid blocker, to mice lacking Nav1.7 and found that they became able to feel pain. They then gave naloxone to a 39-year-old woman with the rare mutation and she felt pain for the first time in her life.
"After a decade of rather disappointing drug trials, we now have confirmation that Nav1.7 really is a key element in human pain," says senior author Professor John Wood (UCL Medicine). "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."
HOW TO STAY YOUNG!
Living longer usually means a longer dotage, but wouldn't it be enticing to extend young adulthood instead? It's such an appealing prospect that scientists who are announcing success with roundworms are keen to be clear they are a long way from achieving it in humans.
"We don't want people to get the impression they can take the drug we used in our study to extend their own teens or early twenties," says lead author Michael Petrascheck from The Scripps Research Institute (TSRI), California.
"We may have done this in worms, but there are millions of years of evolution between worms and humans.
"We think it is exciting to see that extending lifespan by extending young adulthood can be done at all," he says.
In the study to be published in the journal eLife, the TSRI-led team administered an antidepressant called mianserin to Caenorhabditis elegans, a type of roundworm used frequently in research. In 2007, they discovered that the drug increases the lifespan of roundworms by 30-40 percent. Their new goal was to investigate how.
The team treated thousands of worms with either water or mianserin and looked at the activity of genes as the worms aged.
First, they measured the activity of genes in young adults as a reference point against which to monitor the aging process.
Reproductive maturity begins in day-old roundworms and they live for 2-3 weeks on average.
As the worms aged, the team observed dramatic changes in gene expression. However, the changes occurred in a way that came as a complete surprise. Groups of genes that together play a role in the same function were found to change expression in opposing directions.
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