The chronic pain and the various researches that try to alleviate the symptoms, have led to the discovery of one new therapy that could replace opiates. This is stated in a preclinical study conducted by neuroscientists and pharmacologists from the Jacobs School of Medicine and Biomedical Sciences at the University of Buffalo.
There Research was published in the prestigious scientific journal Nature Communications.
New therapy for chronic pain: here’s what the study says
The research has identified two sets of novel lipid peptides, peptides modified with lipid molecules, which are administered directly to the lesion site. With the assistance of UB Business and Entrepreneurial Partnerships, the researchers also formed a startup called Channavix, which is developing non-opioid drugs for chronic pain.
“Our small peptides are able to penetrate nerve endings and provide lasting chronic pain relief after a single administration”, explained the senior author Arin Bhattacharjee, Ph.D., associate professor of pharmacology and toxociology at Jacobs School.
UB researchers were studying sensory neurons called nociceptors, which are activated in response to pain caused by injury: “Pain is generally considered a symptom of injury”, Bhattacharjee said. “Pain neurons relay their information to the brain, informing the brain of both the location of the injury and the severity of the injury. At the molecular level, our research is helping to unravel how tissue lesions signal pain-sensitive neurons. If we can understand this at the molecular and cellular level, we can then identify new pain-relieving targets ”.
Bhattacharjee and the first author Rasheen Powell, Ph.D., they found that To signal pain, a specific type of pain neuron requires endocytosis, the process by which cells engulf materials outside the membrane.
These neurons, called pain neurons, containing calcitonin gene-related peptide (CGRP), preferentially express a specific subunit of endocytosis called AP2A2, which other sensory neurons do not produce.
“This discovery is particularly exciting because a specific subset of pain neurons in the dorsal root ganglia (DRG) in the peripheral nervous system express AP2A2 while other populations of sensory neurons in the DRG do not. “, he said Powell, researcher of the Harvard Medical School Department of Neurology: “This suggests that this subunit plays an important role in these particular pain neurons, which are responsible for most of the inflammatory pain behaviors seen in rodents and humans. “
Using genetic and pharmacological approaches, the researchers found that endocytosis in these neurons was essential for both the development and maintenance of inflammatory pain: “But when we inhibit endocytosis with a genetic or pharmacological approach, we observe profound reductions in pain-suggestive behaviorsPowell specified.
Even under conditions that promote hyperactivity in pain neurons, the researchers found that they could significantly reduce this hyperactivity, and therefore pain perception, when they prevented endocytosis with their new peptide molecule.: “By inhibiting endocytosis, we are able to prevent pain-sensitive neurons from transmitting pain information to the central nervous system“, Continued the expert.
A key advantage of the peptides developed by the researchers is that they disrupt endocytosis when applied locally to pain nerve endings: “In clinical practice, we always use local approaches to block pain“Said Bhattacharjee. “Anesthetics are effective in blocking pain, but the problem is that they block all sensory neurons, so the patient feels numb and they have a very short life. After the anesthetic wears off in a few hours, pain relievers are often needed. We found that when applied topically, our peptide reduced chronic pain behaviors in multiple inflammatory pain patterns for up to six days “, clarified the scholar.
The advantage of locally administered drugs is that most side effects are avoided, especially the risk of addiction. Negative side effects are also one of the main reasons why new drugs often don’t get US Food and Drug Administration approval – local injection of drugs avoids this drawback.
Bhattacharjee noted that local administration of drugs may, however, have its limitations: they tend to spread rapidly away from the site where they were administered. “Our new technology appears to solve this problem by getting into the nerve endings and staying there“, he said. “The result is a lasting reduction in pain behavior.”
UB research also pointed out that males and females experience pain differently. In the animal studies they conducted, if pain was already established, females did not respond as well to the peptide as males. But if the peptide was administered right at the time of injury, females had better pain behavior reduction than their male counterparts.
“These data follow human clinical studies”, Bhattacharjee said, “Where there is a gender difference in both the prevalence and intensity of chronic and postoperative inflammatory pain in humans. This underlines the importance of gender considerations in the development ofanalgesic“.
The researchers intend to focus on the key preclinical formulation and toxicology studies to enable a new investigational drug to be tested in humans.