 Breathing may seem like a simple task, but research has long shown that adequate respiration requires a complex, coordinated effort by multiple regions of the brainstem. This has important implications for research that investigates the respiratory side effects of opioids. Opioids are a common and effective treatment for combating pain in patients undergoing surgery. The use of these drugs, however, is limited by their depressant effect on breathing rate, which can result in dangerously low oxygen levels in patients after surgery. Much research has, therefore, focused on identifying medication that can counteract this complication. However, according to a new study published in the journal Anesthesiology, these efforts may have missed an important region of the brain. For decades, scientists and physicians worked under the assumption that a single area in the brainstem, called the pre-boatsinger complex, was the primary control site of the rate and rhythm of breathing. They also showed that high experimental doses of opioids depressed breathing in this area. But now a team of US researchers has found a second location that is more important at the opioid doses used for pain control in patients. Using a rabbit model, the research team administered intravenous remifentanel, a pain drug often used during surgery until the breathing rate was depressed. They then directly injected the opioid receptor antagonist Naloxone, a drug that mitigates the effect of opioids, in two different regions of the brainstem. They found that the antagonist injection into the parabrakeule nucleus significantly reversed respiratory rate depression caused by the opioid remifentanel, while there was only a minor effect in the pre-boatsinger complex. Knowing where and how opioids interact with the brain and cause reduced rates of breathing gives researchers an important tool in stopping this potentially deadly effect. These results suggest opioids' slow respiratory rhythm by acting on several areas in the brainstem. Given the high rates of opioid overdoses in recent years, this discovery provides important insights to investigators searching for drugs that can reverse respiratory depression without reversing the pain-killing benefits of the medication or causing withdrawal symptoms, an ability that could save thousands of lives every year.