If you’re among the 50 million Americans suffering from chronic pain, you know all too well how a sharp jab in your back or ache in your knee is more than an inconvenience—it affects your everyday life. Despite the marvels of modern medicine, treating it remains challenging due to the complexity of chronic pain and how it's unique to each sufferer. Yet searching for new and safe painkillers is especially important given the toll of the ongoing opioid crisis.
Fortunately, scientists may have found the pain-relieving golden goose, according to a new study published Tuesday in the journal Science Signaling. Researchers at the University of São Paulo in Brazil have created a promising new drug that targets a pathway in the human body that triggers pain sensations. The drug, named TAT-pQYP, provided relief to mice suffering from inflammatory pain, and it may one day be the answer for many different kinds of chronic pain.
There can be a whole host of medical conditions behind pain like disease or physical injury, but the biological reason for those unpleasant twinges is nociceptors, or sensory neurons that detect damage in skin, muscle, bones, and other internal organs. When a nociceptor senses trauma—like when you scald your hand with a hot cup of coffee—it sends the information to the brain and spinal cord for further processing. In the case of burning your hand, as long as the injury isn’t severe and you received timely medical treatment, the raw burning sensation tends to go away on its own. But in some conditions like cancer, multiple sclerosis, arthritis, or serious physical trauma, the pain might not go away. This could be because the nociceptors are kept active by chemical signals like inflammation or there is some sort of damage to the nervous system.
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Over the years, scientists have noticed one shady character cropping up whenever pain does: nerve growth factor (NGF), a protein important to the development and survival of neurons, especially those that transmit sensory information like temperature and pain. In certain conditions like osteoarthritis, NGF can keep nociceptors perpetually on and lead to persistent, chronic pain.
Some treatments tackling the protein head-on are still in development (like antibodies that hunt down NGF and sequester it before it can poke a neuron). But such treatments can have undesirable side effects like preventing neuron growth. Scientists like the University of São Paulo group are trying instead focus on other targets like TrkA, a receptor that’s found on the surface of some sensory neurons and activated by NGF. It can launch a domino effect inside the neuron of other proteins signaling pain.
The researchers looked at the genes of patients who have congenital insensitivity to pain as well as those with anhidrosis, a rare genetic disorder where people affected are unable to feel pain and temperature. The University of São Paulo team found that mutated forms of a gene in these patients prevented TrkA from interacting with another protein called PLCg, and setting off pain alarms.
This gave the research team the idea to build a decoy, dubbed TAT-pQYP, that looks like TrkA but doesn’t allow it to mingle with PLCg. When human embryonic kidney cells in Petri dishes were doused with the new drug, the pain relay wasn’t turned on. When it was injected into mice with inflammatory pain, it appeared to provide relief since the animals didn’t flinch when touched. The drug also didn’t seem to cause any nasty side effects in healthy mice like messing up their tactile perception.
There’s still much more work to be done, so the University of São Paulo researchers caution. TAT-pQYP needs to undergo more lab testing before it can reach clinical trials in humans. And if it does get to that stage, it may take a while for the drug to reach the commercial market if decades-long clinical trials for anti-NGF drugs are any indication. It’s a promising first step, though, in uncovering the why behind pain and spurring further research efforts into NGF. The drug may also provide an alternative to patients who still rely on opioids despite prescriptions in the U.S. tapering off in the past decade due to the ongoing and unprecedented epidemic.
