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Researchers May Have Found the Secret to Painlessness
A study conducted by University College London with funding from the Medical Research Council and the Wellcome Trust may have uncovered the secret to painlessness. By studying mice with a genetic mutation that leaves them unable to feel pain, researchers have found a drug combination that could take pain away altogether.
Pain is transferred to the brain via “channels”, and these are encoded by genes. The mutation that prevents the sensation of pain is a loss of function in the SCN9A gene, which is responsible for encoding the Nav1.7 sodium ion channel. When this channel doesn’t work properly, pain signals do not reach the brain. One of the possible effects of this specific mutation is a congenital insensitivity to pain, which is highly debilitating. However, the existence of this mutation offers hope for those suffering from chronic pain, and this study could also help those incapable of feeling pain at all.
There have been attempts since 2006 – when Nav1.7’s role in pain was discovered – to replicate the painkilling effect using drugs that block the channel. Unfortunately, they were generally unsuccessful. This study found that mice and humans who do not have an effective Nav1.7 channel also produce levels of opioid peptides in their bodies that are higher than the norm. Researchers gave opioid blockers to mice with this condition and found that they were able to feel pain. They then administered an opioid blocker (naloxone) to a woman who, at the age of 39, had never felt pain before. This allowed her to feel pain, and opened up a range of exciting possibilities.
Assessing pain in rodents is no easy task; this is where tools like ActualHCA, which allows 24/7 monitoring and assessment of behaviour, and the Mouse Grimace Scale come in useful. In the UCL study, thermal and brush stimulation were used to trigger a pain response in the mice bred to have the pain-free mutation after they were given naloxone. In addition to observing and assessing the behaviour of the mice, researchers conducted electrophysiological studies using wide dynamic range neurons implanted in the mice’s spinal cords.
As a result of this study, the UCL researchers have filed a patent for a drug that will block pain effectively without the side effects that are a serious downside of opiate painkillers. A combination of Nav1.7 blockers and very low doses of opioids – designed to mirror what is naturally produced by people with non-functioning Nav1.7 channels – will enable effective pain reduction or removal without unpleasant side effects or an increase in patients’ tolerance to drugs.
If all goes to plan, this approach will undergo human trials in 2017. To learn more, read the study in Nature Communications or the article from UCL. For more information about ActualHCA and its use in observing behaviour during pain studies, click here to view our product page or contact us today.