Brazilian scientists from Butantan Institute's Special Pain and Signaling Laboratory (LEDS) have made a discovery that could result in improved painkillers, Phys.org reports.
They discovered a mutation in a part of the human brain that allows us to feel pain. It is called the TRPV1 receptor, which enables humans to detect heat and spicy foods' burning sensation.
The researchers collaborated with scientists from Stanford University, Emory University, and Münster University Hospital to learn about the mutations.
If the researchers can develop painkillers that target this mutation, we may be able to avoid some of the adverse side effects of current pain medications, such as opioids.
Developing Better and More Effective Painkillers
At least 1.5 billion people worldwide suffer from chronic pain, according to Dana.org, and not all types of pain are treatable with currently available painkillers.
In addition, existing research says pain medications can cause dependence and tolerance, particularly morphine and other opioids. Scientists have therefore sought out novel painkillers that can be an alternative to opioids.
The study explains that TRPV1 is a critical heat-signaling channel and that completely altering its activity eliminates physiological pain by interfering with the protective sensation of burning heat.
The researchers examined several human mutations as well as available information about birds, which, unlike mammals, have a TRPV1 receptor.
Numerous drugs resulting from this process interfere with the regulation of body temperature. Nonetheless, the researchers discovered a potential pain insensitivity mutation in the gene encoding this protein, which could be a game-changer in the search for new and better painkillers.
Mutations to Develop Better Painkillers
The researchers started by looking through a genome database and comparing the genetic sequences of avian and human TRPV1. Using a computational approach, they identified five avian mutations that they suspected were linked to pain resistance.
Cryogenic electron microscopy revealed that the five avian mutations were found in K710, an amino acid residue that controls TRPV1 channel gating (opening and closing).
The scientists then discovered that capsaicin, the molecule responsible for the spiciness of chili peppers, activates TRPV1.
In experiments on mice, researchers found that certain mutations in this receptor can reduce the pain caused by capsaicin.
To investigate further, the scientists used a gene-editing tool called CRISPR to create mice with one of these mutations. They found that these mice had less sensitivity to pain caused by nerve injury and were less bothered by capsaicin in their food.
Also, blocking this receptor in normal mice reduced their sensitivity to pain. These findings could lead to the development of new pain-relieving drugs that target this receptor.
TRPV1 not only modulates pain but also protects against other stimuli. Recent evidence suggests it acts as an intracellular molecular sensor in non-neuronal cells, protecting against glucose-induced cellular stress or tissue ischemia.
"We now want to add value to this study by validating the results under best-practice laboratory conditions, identify other small molecules besides the peptide that can more easily be synthesized, conduct preclinical trials, and, if these are successful, begin a clinical trial," said Vanessa Olzon Zambelli, a researcher at LEDS and co-first author of the article.
Stay posted here at Tech Times.
Related Article: Researchers Develop New Drug Delivery Approach for Brain Tumor Treatment Among Children
