Brazilian scientists from the Butantan Institute’s Special Pain and Signaling Laboratory (LEDS) have come up with discoveries which could lead to better drugs for treating pain, Phys.org reports.
The researchers discovered a mutation within our brain which permits the brain to sense pain. It’s called the TRPV1 receptor. It allows humans to feel the heat and the spicy food’s burning sensation.
Researchers collaborated with researchers at Stanford University, Emory University, and Munster University Hospital to learn about genetic mutations.
If researchers can develop painkillers that specifically target the mutation in question, we might be able to eliminate the adverse effect of current anaesthetics, including opioids.
Making Better and More Effective Painkillers
At the very least, 1.5 billion people worldwide have chronic pain. According to Dana.org, most kinds of pain are manageable by painkillers.
Furthermore, current research indicates pain medications could create tolerance and dependence, specifically morphine and opioids. Researchers have therefore searched for new painkillers that could be alternatives to opioids.
The study explains that research explains the fact that TRPV1 functions as an essential heat-signalling channel and that altering its function eliminates physical pain by interfering with the sensation of protection against burning heat.
The researchers looked at various human genetic mutations and the available information on birds, which, in contrast to mammals, possess a TRPV1 receptor.
Many drugs that result from this process affect the body’s temperature regulation. The researchers did discover an underlying pain-related modification in the gene that codes this protein. This could revolutionize the search for more effective and more effective painkillers.
Changes to develop better painkillers
The researchers began by going through an entire genome database and then studying the genetic patterns of the avian and human TRPV1. Utilizing a computer-aided approach, they discovered five avian mutations they believed were related to the resistance to pain.
Cryogenic electron microscopy showed these five mutations had been identified in K710, the amino acid residue that regulates TRPV1 channel closing and opening (opening and close).
The researchers then discovered that capsaicin, the chemical responsible for the spicy taste of chilli peppers, triggers TRPV1.
Through experiments with mice, researchers discovered that specific mutations to this receptor could lessen the pain caused by capsaicin.
To further investigate, researchers used a tool for editing genes known as CRISPR to create mice that had the mutation. They discovered that the mice were less sensitive to nerve injuries and less susceptible to capsaicin present within their meals.
In addition, blockade of the typical receptors in mice decreased their sensitivity to pain. This could lead to the development of pain-killing medications that target this receptor.
TRPV1 is not just a pain modulator but also defends against other triggers. It protects against cellular stress caused by glucose or tissue ischemia. Recent research suggests it functions as a molecular sensor intracellularly within non-neuronal cells.
“We are now looking to add the value of this study by verifying the results in best-practice laboratory conditions, identifying other small molecules, other than the peptide that could more easily be made, as well as conducting preclinical tests and, if successful, we will begin an actual clinical trial” stated Vanessa Olzon Zambelli, a researcher at LEDS and co-first author the paper.