CBNS researchers have revealed how an important pain receptor in the body works, potentially leading to the development of new drugs for strong pain relief without the side effects and addiction associated with current pain medications like morphine and oxycodone. Using nanoparticles, the researchers have developed a therapeutic strategy that potentially dampens this pain, and through its ability to more effectively enter the nerve cells, leads to prolonged pain relief.
The research may open the way for new ways to treat visceral pain such as that seen in endometriosis, period pain, irritable bowel syndrome and colitis.
The study found that stimulating the delta opioid receptor in the nerve cells of the gut led to a reduction in pain. While known as a pain receptor, delta has remained relatively unresearched compared to the well-known mu opioid receptor, which is the target of most currently available opioid-based pain medications and is associated with opioid addiction.
The research, published in the Proceedings of the National Academy of Sciences in the US, is led by researchers from CBNS, Dr Daniel Poole and Dr Nicholas Veldhuis. According to Dr Poole, “we have shown that these delta opioid receptors have a built-in mechanism for pain relief and can be precisely targeted with drug-delivering nanoparticles—making them a promising target for treating chronic inflammatory pain with fewer side effects,” he said.
Opioid receptors—which are primarily located throughout the central nervous system and gut—relieve pain when they are activated by opioids, both those naturally produced by the body and those taken as medications.
While there are several types of opioid receptors, the majority of opioid medications like oxycodone and morphine act on the mu opioid receptor. Opioid medications have significant side effects mediated by the mu opioid receptor, including constipation and difficulty breathing. These drugs are addictive and their effectiveness diminishes over time, so people require higher doses to manage their pain, leading to increased side effects and risk of overdose.
Using biopsies from the colons of people and mice with ulcerative colitis, an inflammatory bowel disease, the researchers discovered that the delta opioid receptor provides a built-in mechanism to relieve inflammatory pain. The inflammatory cells from the colon release their own opioids, which activate the delta opioid receptor and block the activity of nerves in the gut that are known to transmit painful signals – essentially silencing the pain.
Importantly, the researchers found that delta opioid receptors located at the cell surface of nerve cells provide partial relief from pain, but produce much greater pain relief when they move to the inside of these cells – meaning targeting these “internal” receptors with a drug will lead to prolonged pain relief, according to Dr Veldhuis. “By getting potential drugs to be absorbed into the interior of nerve cells to trigger these delta receptors could lead to long term, sustained, pain relief,” he said.
To target the delta opioid receptor, the researchers encapsulated a painkiller called DADLE, which binds to the delta opioid receptor, inside nanoparticles—microscopic vehicles used to deliver drugs to cells. They then coated the nanoparticles with the same painkiller, which steered the nanoparticles specifically to nerve cells that control pain and away from other cell types, avoiding side effects. According to Professor Nigel Bunnett, a Partner Investigator of the CBNS at New York University, when the nanoparticles entered the cells to reach cellular sites known as endosomes, they slowly released the painkiller to activate the delta opioid receptor more effectively than when the same drug was administered with the use of a nanoparticle. “This resulted in a long-lasting activation of the delta opioid receptor, suggesting a sustained ability to inhibit inflammatory pain,” he said.
“Our findings demonstrate that not only are delta opioid receptors in endosomes a built-in mechanism for pain control, but a viable therapeutic target for relief from chronic inflammatory pain.”.
Herald Sun, Melbourne by Alanah Frost - 03 Aug 2020 General News - Page 13 - 164 words - ID 1311155877 - Photo: No - Type: News Item - Size: 92.00cm2