(December 5, 2015) 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.”
Broad-spectrum sodium channel blockers are used as local
anaesthetics, but they are not suitable for long-term pain management as they
cause complete numbness and can have serious side-effects over time. By
contrast, people born without working Nav1.7 still feel non-painful touch
normally and the only known side-effect is the inability to smell.