While opioids such as fentanyl and oxycodone are among the most potent medicines known to modern medicine, they are also incredibly addictive and hence more difficult to get – even for individuals in severe pain. A new discovery may give pain patients hope in the form of potent medications that lack the most difficult-to-manage side effects of current alternatives.
Pharmacologists long ago discovered that drugs that act on opioid receptors on nerve cells work best for blocking pain. However, as seen by the present opioid crisis, these medicines are highly addictive. There are two types of opioid receptors in our neurons, and the most addictive medications target the mu receptors. In order to identify alternatives to these drugs, scientists focused on the kappa receptors. However, medicines that target these circuits have their own set of adverse effects, most notably hallucinations.
Nonetheless, because addiction is not a problem, dealing with the kappa receptors has shown promise. Researchers at Washington University School of Medicine and the University of Health Sciences & Pharmacy in St. Louis have discovered that there are several types of kappa receptors. More crucially, they observed that while all of them can provide some pain relief, not all of them create hallucinations.
The key is a class of signaling molecules known as G proteins. When these proteins come into contact with kappa opioid receptors, they activate distinct pathways. The study team hopes that with more testing, they will be able to determine which pathways give pain relief without causing hallucinations. Once that issue is solved, it should be able to develop medicines that function as well as the greatest opioids while avoiding their hazardous side effects.
“All of these proteins are similar to one another, but the specific protein subtypes that bind to the kappa receptor determine which pathways will be activated,” said Tao Che, an associate professor of anesthesiology at WashU Medicine. “We discovered that hallucinogenic drugs preferentially activate one specific G protein but not other, related G proteins, implying that beneficial effects like pain relief can be distinguished from side effects like hallucinations.” As a result, we anticipate that treatments that stimulate the kappa receptor to eliminate pain without simultaneously activating the particular pathway that produces hallucinations will be developed.”
The recent discovery adds to past studies attempting to replace opioids with safer alternatives. A 2018 research, for example, reported that a non-addictive painkiller was successful in non-human primates, while a more recent study indicated that three earlier antibiotics were useful in reducing neuropathic pain in mice. There is even speculation that a chemical found in spider venom might one day lead to non-addictive medications. Given that over 70,000 people died from opioids other than methadone in the United States alone in 2021, any compound that can provide pain relief without causing addiction or other serious mental health consequences would be a welcome addition to the current state of pain management.
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