Drug Abuse: The abuse of opioids, whether of prescription opioids or heroin, is reaching epidemic proportions in the USA. Epidemiological data collected by the CDC show a ~100 fold increase in mortality from prescription opioids and a ~400 fold increase from heroin over the past 15 years. Together these opioids account for 3 deaths per hour. Yet we know very little about the processes that drive the craving for opioids and relapse. We are finding that it is the negative effect induced by the lack of the drug that is as or more important than the positive effect felt when the opioid is taken.
Opioid receptors: After many years of studying the opioid receptor family, we have a good understanding of how they function normally, which molecules they interact with, the channels they inhibit and how they signal to relieve pain or induce euphoria. One of the interacting molecules we study is the arrestins, important scaffolding and signaling molecules. We have outlined, and continue to outline, the unique roles of these molecules in controlling opioid receptor trafficking and function. More recently we have been examining how these arrestin 1 also regulate glutamatergic signaling and the response to abused drugs.
Optogenetics: Using genetically modified neurons, expressing light sensitive receptors, we activate specific cell types and perform various behavioral tests, revealing their function in forming habit behaviors, such as drug addiction.
Opioids and chronic pain alter brain connectivity: Opioids such as morphine alter the shape of cells. This could affect how cells of the brain connect and communicate with each other. We have been using a novel retrogradely transported virus to map cell-cell connections in the striatum, an important hub of drug abuse behaviors and also of the emotional effects of chronic pain. This virus expresses the Brainbow cassette and changes color if the enzyme Cre Recombinase is present. We then map where the virus has traversed so as to generate a comprehensive view of how opioid abuse and chronic pain alter specific striatal circuits.
Chronic Pain: While acute pain is a normal sensation triggered by the nervous system as an alert to possible injury, chronic pain persists beyond the expected period of healing. During chronic pain, signals fire in the nervous system for up to weeks, months, even years. Three million new case of chronic pain occur every year and result in billions of dollars in expenses annually. We work on the adaptations to chronic pain, in particular that of the mu opioid receptor. Signaling at this receptor normally induces pain relief. We have found that this receptor begins to signal continuously in chronic inflammatory or neuropathic pain and that this provides a fragile recovery from chronic pain. We are now working on how this occurs and whether this can be used to treat chronic pain.