Mechanisms of Affective States and Drug Discovery at the Intersection of Chronic Pain and Opioid Addiction

2021 Scientific Innovations Award
Gregory Scherrer, Ph.D.
The University of North Carolina at Chapel Hill

Pain is normally a sensation that we experience when our body is exposed to damaging stimuli, such as the noxious heat of an open flame. However, when chronic, pain becomes a debilitating disease. Injury or disease can change how pain neural circuits function: pain can then be perceived spontaneously in the absence of actual stimuli, and normally innocuous stimuli such as light touch can generate excruciating pain. The National Academy of Medicine revealed the outstanding magnitude of the problem, with 116 million Americans suffering from chronic pain. Furthermore, in the absence of efficient alternative treatments, do use of opioids for pain management has increased dramatically in recent decades, driving an Opioid Epidemic with alarming augmentations in the cases of addiction and overdose, from which about 50,000 Americans die every year. A better understanding of the mechanisms underlying chronic pain is urgently needed to develop safer analgesics. Previous efforts to focus on blocking the transmission of pain information within nerves or spinal cord circuits; however, this strategy has not led to novel effective painkillers. Here Dr. Scherrer’s lab proposes a different approach: to alter our brain’s interpretation of peripheral pain signals in order to eliminate pain unpleasantness and restore patients’ quality of life. Indeed, pain unpleasantness causes the majority of suffering for chronic pain patients, and often results in reduced mobility, social isolation and psychiatric comorbidities including anxiety and depression. Dr. Scherrer’s laboratory aims to discover drug targets that are present in the brain’s neurons that generate pain unpleasantness but are absent from the reward and breathing neurons affected by opioids, with the goal of developing a completely novel and safer class of analgesics. If they succeed, the experience of chronic pain will be largely limited to sensations localized at the site of injury and would no longer be associated with debilitating negative emotions. In the future, they will determine how opioids change how the brain works to identify novel drug targets against drug addiction. In summary, this research the potential to end the Opioid Epidemic.

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