AUG 23, 2019 07:29 AM PDT

Making Opioids Safer

The opioid crisis results in 130 American deaths every day, and both prescribed and synthetic opioids are at the core of the epidemic.  Any other drug that posed such liability would likely be taken off the market, but opioids are unmatched at tackling the most basic aliment: pain.  

Opioids are so effective at mitigating pain because they target "Micro-Opioid Receptors" (MORs), located in the area of the brain stem called the Periaqueductal Gray (PAG).  The PAG is responsible for inhibiting pain signals transmitted to the brain, acting a brake so that the brain is not inundated with pain signals.  

Scientists at Scripps Research are trying to combat patient pain and limit the dangers of opioids.  By following the mechanism of opioids in the brain, the researchers were able to identify genes that dial the effects of the drug.  

The researchers started with a genomic assay to find all genes involved in the body's response to opioid exposure.  This "unbiased" search resulted in a list of specific genes for the team to monitor during exposure to opioids.  

The nematode worm, Caenorhabditis elegans, was used to test the response to opioids.  C. elegans does not naturally have any response to opioid exposure, so the worms were modified with the addition of such response genes.  The genetic modification worked because the worms had a familiar response to opioid drugs:  decreased pain, heavy dependence, and severe withdrawal symptoms.  

C. elegans source:  Society for Mucosal Immunology.

 

Next, the researchers monitored genes related to the physical response of opioids and isolated a protein called FRPR-13.  The equivalent in humans, GPR139, is made simultaneously with the MOR group of receptors.  However, the expression of GPR139 inhibits MORs, blocking opioids from activating the receptors.  

For example, mice that produce excess GPR139 and are dependent on opioids, choose to stop taking the drug because the receptors cannot signal a need for it.  Removal of GPR139 amplified addictiveness and pain-killing effect of opioids, but also eliminated withdrawal symptoms.  

Researchers believe eliminating GPR139 could be the key to making opioids safer to use.  The elimination of the protein not only makes opioids a better pain killer but without any withdrawal symptoms, the barriers to ending addiction disappear.

Scientists hope this research will lead to a solution to end the opioid epidemic and provide a powerful alternative for legitimate medical pain.  Understanding the mechanisms of pain inhibition, MORs, and GPR139 is a big step in solving these problems.  

 

Sources: Centers for Disease Control and Prevention, Nueroscientifically Challenged, ScienceDaily, Science  

About the Author
  • Intern research scientist genetically engineering yeast to making a renewable fuel. Interested in food/water security, sustainable fuel, and sustainable farming.
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