Uncontrolled pain costs over $500 billion annually in medical expenses, disability programs and lost productivity. The management of pain is complex and increased treatment with opioids has contributed to an epidemic of addiction and overdose deaths. Although much of this crisis has been contributed to the inappropriate prescribing of opioid drugs for moderate pain, opioids continue to be the most effective treatment for debilitating chronic pain. Findings from two recent studies published in Neuron (https://doi.org/10.1016/j.neuron.2021.10.019) and Nature Neuroscience (https://doi.org/10.1038/s41593-021-00973-8), could help lead us out of the opioid epidemic by uncovering unknown mechanisms of pain and potential alternatives to opioid treatment, respectively. In the Neuron study, investigators used calcium imaging techniques to show that spontaneous pain, like the type commonly experience by patients with chronic pain after injury, may be due to clusters of pain sensing neurons (nociceptors) firing in synchrony. Moreover, this firing may be initiated by nerves from the sympathetic nervous system, which is responsible for our “fight or flight”, or stress, response. After injury, these sympathetic nerves appear to regrow in an abnormal way, which may lead to triggering spontaneous pain when a patient is stressed. In the study published in Nature Neuroscience, researchers showed that components of the toxin produced by the anthrax bacterium can reduce pain in mice. Furthermore, the toxin can and be targeted specifically to nociceptors, preventing potential negative side-effects on the brain, unlike opioids. This summer, students in Dr. Cheryl Wotus’ biology course, Neurobiology of Pain (Biol 3910), will be reading more about studies such as these, as well as learning about the mechanisms of opioid addiction and its treatment.