In a recent paper published in Cell Reports, Manoj Puthenveedu (CMU Biology and CNBC) and colleagues report how pain fine-tunes the responses of sensory neurons to opioid analgesics, medications that relieve pain. A constant problem that clinicians face is to use analgesics in a way that avoids a patient’s development of tolerance to the drug (decreasing its potency) as well as addiction. The report sheds light on how pain signals can directly modify the cellular targets of opioids and change their cellular location in neurons. Puthenveedu and colleagues noted that the change increases the sensitivity of sensory neurons to some opioids like endorphins and fentanyl, but not morphine, and reduces acute tolerance to fentanyl, but not morphine, in animals. These results add important data to understanding the clinically important question of the varied effects of opiods on neurons. For more information, see here.