Papers of the Week

Opioid overdose is due to misuse of prescription pain killers such as oxycodone, as well as misuse of street drugs like heroin or fentanyl. Opioid overdoses are responsible for the deaths of over 50,000 persons annually in North America. Opioid drugs are highly addictive and can lead to respiratory depression and death. Although opioid addiction is a critical health issue, the morbidity and mortality associated with opioid overdoses are due to their respiratory depressant side-effects, and not addiction per se. Even though respiratory depression and complete respiratory arrest are the major causes of mortality with opioid overdose, there is currently a serious knowledge gap in our understanding of the underlying mechanisms of opioid pain relief and respiratory depression by opioids, and how these mechanisms differ from each other. We propose that there should be a greater research focus on these mechanisms in order to help develop safer opioid pain therapies with reduced respiratory side-effects. Here, we provide a brief overview of current research investigating the neural and molecular mechanisms underlying opioid-induced respiratory depression and analgesia. We focus our attention on the neural circuits of analgesia and respiratory depression, and the molecular pathways regulating opioid inhibition. We highlight the challenges in identifying distinct mechanisms that could be targeted to reduce respiratory depression without altering opioid analgesia. In conclusion, a better understanding of the underlying mechanisms linking pain relief with control of breathing is essential to identify pain therapies with minimal or no respiratory side-effects.