By David Kipkorir
Scientists have identified the neurons and receptors that disrupt breathing during opioid overdose. The findings are expected to lead to better treatment options for opioidinduced respiratory depression (OIRD). They discovered that blocking specific receptors in these neurons can restore breathing.
Opioid overdose deaths are caused by disrupted breathing, termed opioidinduced respiratory depression (OIRD). It has been unclear how opioids suppress respiration. Researchers from the Sulk Institute (CA, USA) have identified a group of neurons in the brainstem that play a key role in the process and have shown that blocking receptors in these neurons can cause OIRD to be reversed.
Senior team researcher Sung Han noted that underlying mechanism of why opiates slow down and depress the breathing rhythm has not been fully characterized. Opioids are highly addictive painkillers that have resulted in what is termed the ‘opioid epidemic’.
There is limited research on opioid use in Africa but it has been shown to be an emerging problem. In Kenya, studies show that there is opioid use in the general population aged 15-65 years. Opioid use accounts for most of the negative effects of substance use. These include; increased risk for infections such as HIV and hepatitis, increased involvement in crime, unemployment and increased mortality.
In addition there is significant economic burden associated with opioid use due to cost of hospital visits, loss of productive work. Kenyan researchers have noted in the past that HIV prevalence rate among people with injection drug use is three times that in the general population.
Opioids bind to opioid receptors on neurons and inhibit their activity, subsequently relieving pain. Naloxone is the only medication known to treat an opioid overdose, but it works systematically by blocking opioid receptors throughout the body, including those that control pain.
The study, published in Proceedings of the National Academy of Sciences, identified a group of neurons in the brainstem breathing modulation center that expressed a specific type of opioid receptor called mu opioid receptor. The researchers found that when mice that had been genetically engineered to lack these receptors were exposed to morphine, their breathing was not disrupted, unlike mice in the control group.
They also found that, even in the absence of opioids, stimulating the mu opioid receptors in the control mice induced OIRD. The researchers discovered that they could reverse OIRD in overdosed mice by treating them with chemical compounds that targeted other receptors on the neurons, activating the neurons.
“We discovered four different chemical compounds that successfully activated these neurons and brought back the breathing rate during OIRD,” explained first author Shijia Liu. In the future, the team hopes to identify other cell groups that may also play a role in OIRD, and further understand the connection between breathing regulation and pain perception in the brain.
“We hope to explain the painbreathing segregation at the molecular or microcircuit level. By doing that, we can try to restore breathing without touching analgesic effects of opioids,” concluded Han. While developing new treatments for OIRD and opioid overdose does not directly address the cause of the opioid epidemic, it could help ensure that fewer lives are lost