Substituting chronic pain relievers could curb the opioid crisis

If you’re among the 50 million Americans who suffer from chronic pain, you know all too well that a stab in your back or aching knee is more than an inconvenience — it affects your daily life. Despite the wonders of modern medicine, its treatment remains challenging due to the complexity of chronic pain and how it is unique to each individual sufferer. However, the search for new and safe pain relievers is particularly important given the ongoing opioid crisis.

Fortunately, scientists may have found the golden gooseberry to relieve pain, according to a new study published Tuesday in the journal Nature. Science. Researchers at the University of São Paulo in Brazil have created a promising new drug that targets a pathway in the human body that causes pain. The drug, called TAT-pQYP, helped relieve pain in mice with inflammatory pain, and it may one day be the answer to many different types of chronic pain.

There can be a wide range of medical conditions behind the pain such as illness or physical injury, but the biological reason for those unpleasant aches and pains is that the receptors or sensory neurons develop. shows damage to the skin, muscles, bones and other internal organs. When a receptor senses an injury — like when you burn 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 hand burns, as long as the injury is not serious and you get prompt medical treatment, the raw burning sensation tends to go away on its own. But in some conditions like cancer, multiple sclerosis, arthritis, or a serious physical injury, the pain may not go away. This could be because the receptors are kept active by chemical signals such as inflammation or there is some kind of damage to the nervous system.

For years, scientists have noticed a shadowy figure that pops up whenever pain strikes: nerve growth factor (NGF), a protein vital to growth and survival. neurons, especially those that transmit sensory information such as temperature and pain. In certain conditions such as osteoarthritis, NGF can permanently disable the receptors and lead to persistent, chronic pain.

Some treatments that address the protein’s head are still in development (like antibodies that look for NGF and isolate it before it can puncture a neuron). But such treatments can have unwanted side effects such as blocking nerve cell growth. Scientists like the University of São Paulo team are trying to focus on other targets such as TrkA, a receptor found on the surface of some sensory neurons and activated by NGF. It can trigger a domino effect inside the nerve cells of other proteins that signal pain.

The researchers looked at the genes of patients who are congenitally insensitive to pain as well as patients with a rare genetic disorder where affected people are unable to feel pain and temperature. The University of São Paulo team found that mutated gene patterns in these patients prevented TrkA from interacting with another protein called PLCg and setting pain alerts.

This gave the team the idea of ​​​​making a decoy, named TAT-pQYP, that looks like TrkA but doesn’t allow it to mix with PLCg. When the human embryonic kidney cells in the Petri dish were administered the new drug, the pain receptors were not turned on. When it was injected into mice suffering from inflammatory pain, it seemed to relieve pain because they didn’t flinch to the touch. The drug did not appear to cause any unpleasant side effects in healthy mice such as disturbances in their tactile perception.

Much work remains to be done, so University of São Paulo researchers beware. TAT-pQYP needs to undergo more laboratory testing before it can be clinically tested in humans. And if it gets to that stage, it could take some time for the drug to reach the commercial market if decades-long clinical trials for anti-NGF drugs are any indication. However, it is a promising first step in discovering why behind the pain and spur further research efforts on NGF. The drug could also provide an alternative for patients who are still taking opioids despite a steady decline in prescriptions in the US over the past decade due to the ongoing and unprecedented epidemic.