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 we propose 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. Our 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 we 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, we 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.

Other Awards

Angelique Bordey, Ph.D., Yale University
The Role of Ribosomes in Synaptic Circuit Formation and Socio-Communicative Deficits
Our proposal aims at identifying a molecular mechanism responsible for autism-like socio-communicative defects in the developmental disorder, tuberous sclerosis complex (TSC). TSC is a genetic disorder with a 30-60% incidence…
Adam E. Cohen, Ph.D., Harvard University
To spike or not to spike? Mapping dendritic computations in vivo.
The brain is made of neurons, and neurons convert synaptic inputs to spiking outputs. How does a neuron decide when to spike?
Gina Turrigiano, Ph.D., Brandeis University
Homeostatic Maintenance of Neocortical Excitation-inhibition Balance by Ciliary Neuropeptidergic Signaling
Brain circuit wiring is adjusted during adolescence to generate fully functional circuits, and this process depends on an interaction between genetics and experience. During this period of experience-dependent development, excitatory…
Shigeki Watanabe, Ph.D., Johns Hopkins University
Intrinsic and Extrinsic Mechanisms Underlying Synaptic Proteostasis
Waste management and sustainability are major challenges humans face in the 21st-century. As you concentrate and think about these issues, nerve cells in your brain must deal with the exact…