Researchers investigating the role of ion channels in shifting sodium from one sensory nerve to another have identified a drug that can treat people with congenital insensitivity to pain (CIP) - a rare condition that causes them to be physically incapable of feeling pain.
Not only has the discovery allowed a 39-year-old woman to feel pain for the first time in her life, but the team says the drug naloxone - usually prescribed to treat overdoses of morphine and heroin - could also be used to combat chronic pain conditions such as arthritis.
The sodium ion channel in question is called Nav1.7, and in most people it's expressed at high levels in two types of neurons located in the spinal cord. Encoded by the SCN9A gene, these Nav1.7 channels are responsible for getting signals about physical pain and impending stress and danger to the brain.
But some people are born without these channels, which means their bodies are unable to communicate instances of physical pain to the brain. While this might sound awesome, it's really not. While patients are otherwise healthy, typically showing no signs of physical deformities, they're frequently hurting themselves without knowing it, which can lead to some very serious injuries.
There are reports of babies chewing on their fingers and toes until they bleed, and children biting the tips of their own tongues off because they don't know what they're doing is detrimental to their heath. Infections and broken bones are left to spread or get worse, and diseases can become very severe due to a lack of treatment.
Having CIP would seriously suck, but the mechanisms behind it could be the key to better pain treatment in the future. For years, researchers have been investigating compounds that block the activity of Nav1.7 channels to mimic the effects of CIP in people living with chronic pain, but despite the fact that pharmaceutical companies have been throwing money at the pursuit, no real effective drug candidate has be identified.
"It looked like a fantastic drug target," John Wood at University College London told New Scientist. "Pharma companies went bananas and made lots of drugs."
Wood and his colleagues decided to go back to the source, and genetically engineered mice without Nav1.7 channels - in other words, they made mice with CIP so they could get a better understanding of the condition before trying to develop a drug based on it. The mice showed no response to pain, tested by exposing their tails to very hot or cold temperatures.
In studying the CIP mice, the team found that they were producing a much higher than normal dose of natural painkillers called opioid peptides. Humans also produce these peptides, so the scientists suspected that CIP patients without Nav1.7 channels were producing too many opioid peptides just like the mice, which prevented them from feeling pain.
Because the drug naloxone is designed to block opioid receptors, the researchers figured that if given to CIP patients, it could stop the effects of too many opioid peptides in CIP patients and restore the feeling of physical pain. The drug gave the CIP mice the ability to feel pain for the first time, and when given to a 39-year-old human CIP patient, it had a similar effect - she felt pain when her skin was burnt with a laser.
While the drug looks like a good candidate to treat CIP patients, more research needs to be done into the effects of long-term use. Wood and his team are now looking into the possibility of using the drug to get the opposite effect, Hamzelou reports:
"When his team gave mice Nav1.7 channel blockers together with opioid drugs, they managed to stop them feeling any pain.
The mice in this experiment felt as little pain as mice who lacked the Nav1.7 channel naturally, says Wood. He has taken out a patent on the use of the two drugs for pain relief."
The results have been published in Nature Communications.