People born with a rare genetic mutation are unable to feel pain, but previous attempts to recreate this effect with drugs have had little success. However, University College London (UCL) researchers may have discovered the recipe for painlessness.
Channels that allow messages to pass along nerve cell membranes are vital for electrical signaling in the nervous system. In 2006, it was shown that sodium channel Nav1.7 is particularly important for signaling in pain pathways, and people born with nonfunctioning Nav1.7 do not feel pain. Drugs that block Nav1.7 have since been developed, but they have disappointingly weak effects.
The results of the UCL study, published in Nature Communications, reveal that 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 that lacked 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.
“We now have confirmation that Nav1.7 really is a key element in human pain,” said senior author John Wood, PhD, a professor at 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 anesthetics, but they are not suitable for long-term pain management because they cause complete numbness and can have serious side effects over time. By contrast, people born without working Nav1.7 still feel nonpainful touch normally, and the only known side effect is the absence of the sense of smell.
Opioid painkillers such as morphine are highly effective at reducing pain, but as the body becomes used to the drug, it becomes less effective, so higher doses are needed for the same effect, side effects become more severe, and eventually it stops working altogether.
“Used in combination with Nav1.7 blockers, the dose of opioid needed to prevent pain is very low,” explained Wood. “People with nonfunctioning 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.”
This article was adapted from information provided by UCL.
