Nature has a way of healing things, and the same rings true when people use nature to deal with whatever is ailing them. Whether in their natural or changed state, nature has proven to have solutions to the world’s ailments, including how to treat pain.
While the boy has its very own opioid system that can regulate its response to pain, there are a number of opioid medications that work precisely to relieve pain, but these opioid drugs often have negative long-term side effects.
Aside from addiction, the scavenger receptors can also adversely affect the natural effectiveness of the body’s own ability to produce opioids.
In this new study, it explains how the Conolidine compound found in the pinwheel flower manages to only bind to one specific scavenger receptor. By blocking this particular scavenger receptor, scientists hope that it can no longer stop the naturally produced opioids from collaborating with the other opioid receptors that bolster pain relief.
When it comes to the opioid system of the human body, it is made of receptors, proteins, and other compounds where every single one plays a critical role in helping control people’s pain responses, as well as their behaviors towards the rewards and the addictions to them as well.
Furthermore, aside from the body’s proteins called opioid peptides, which it naturally produces, there are also opioid analgesic medications. These drugs include oxycodone and morphine, medicines that doctors normally prescribe when treating chronic pain.
It’s important to note that these kinds of medications that imitate the responsibilities of the opioid peptides can also produce considerable side effects when taken in high quantities or habitually. When taking too much or too often, they have the chance to cause constipation, nausea, respiratory depression and worse yet, they are incredibly addictive in nature. In fact, the abuse of opioids have led to increased rates of overdose, many of which ended up in death.
According to the National Institute on Drug Abuse, ‘in 2019, nearly 50,000 people in the United States died from opioid-involved overdoses.’ It’s become an true public health crisis for the country that has been linked to disparities of race and economic status which the country has been struggling to deal with. One solution to this major issue is by finding new and alternative therapy options to treat chronic pain.
A new study in the Signal Transduction and Targeted Therapy journal talks about how the ‘plant-derived compound called conolidine might work to increase opioid peptides’ pain-regulating activity’ which could then be used as a safer substitute to opioid drugs.
The collaborative study was conducted by scientists from the Center for Drug Discovery at RTI International in North Carolina, as well as those from the Immuno-Pharmacology and Interactomics group of the Luxembourg Institute of Health (LIH).
Kinds of Opioids and Opioid Receptors
The body has opioid peptides which interact and bind to classical opioid receptors. The four classical opioid receptor types are found within the central and peripheral nervous systems. When the opioid peptides interact with the classical receptors, they generate a surge of protein signaling functions that ultimately induces pain relief.
Yet, the same LIH research group conducted an earlier study that identified ACKR3, which is an atypical opioid receptor. This particular receptor also binds to opioid peptides, yet rather than bringing about pain relief, it actually traps the peptides and stops them from binding to the classic receptors. When this happens, it prevents any chance of pain modulation or therapy.
Moreover, the research group also found high levels of the ACKR3 receptor in vital brain regions which are known to be key opioid activity centers. The scientists labeled them as “opioid scavengers” since they have the ability to entrap the natural opioids before they communicate with the classical opioid receptors.
The Key Molecule for Pain, Conolidine
Looking further into this, this new study decided to look into conolidine. It’s a molecule that can be found in the bark or the pinwheel flower often used in traditional Chinese, Thai and Ayurvedic medicine because of the analgesic properties that it has.
Researchers did a screening test that involved over 240 receptors and what they found was that conolidine showed how it binds to ACKR3 receptor in humans and in mice, stopped the ACKR3 from attaching to opioid peptides.
In addition, they also found that the conolidine molecule didn’t interact with the classical receptors. What this meant is that ‘it would not compete against opioid peptides to bind to these receptors.’
What their study outcome proposes is that the conolidine molecule can ‘restrict the ACKR3 receptor’s negative regulatory properties and free up opioid peptides, allowing them to bind to the classical opioid receptors and promote analgesic activity.’
Thrilling and New Treatment Possibilities
The research group decided to find ways to extend their findings by modifying conolidine chemically in order to create a new compound, RTI-5152-12. The new compound specifically binds to the ACKR3 receptor, which unlike the natural conolidine, this synthetic compound also demonstrated its capacity to be a highly effective treatment option.
In the LIH press release, it shared that the two research teams that worked together also filed a joint patent application for the RTI-5152-12 back in December of 2020.
What the study authors share is “Overall, the discovery of the potential mode of action of conolidine and its activity on ACKR3 is a significant step forward toward a more exhaustive understanding of its role in pain regulation, bearing a great potential for novel drug development against chronic pain.”
The study also recognizes the interrelationship of ACKR3 and conolidine, although what’s not yet clear is ‘the mechanism of action following the binding interaction.’ Despite that, the conolidine mechanism could have much less minimal side effects as compared to opioid drugs, which gives them bigger access to the opioid system and ways to treat the opioid crisis through alternative therapies.
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