Jamie Moffa
Program: Neurosciences
Current advisor: Bryan Copits, PhD
Undergraduate university: University of Connecticut
Research summary
Chronic pain—pain in the absence of physical injury—is a debilitating condition that affects more than 50 million people in the United States every year. Under normal circumstances, the brain integrates nociceptive information with other environmental cues and internal emotional states to modify pain intensity and behavioral responses in a process called descending pain modulation. Dysfunction in descending pain modulation is implicated in the development and maintenance of chronic pain conditions.
The rostral ventromedial medulla (RVM) is a key hub in this system, receiving inputs from other pain-responsive brain regions and sending projections to the spinal cord, where it can modify information coming from peripheral pain-sensing neurons. While activation of mu opioid receptors (MOR) in the RVM strongly inhibits pain responses, the RVM has both pain-faciliatory and pain-inhibitory roles which can be directly modified by pain state. Thus, we currently lack a detailed understanding of how opioid signaling in the RVM mediates this descending analgesia. This is in part due to a lack of tools to understand the role of MOR signaling in specific neuronal populations within the RVM.
In my thesis, I present a single viral vector strategy for gene knockout and expression of commonly used tools for neuroscience, such as fluorophores, calcium indicators, or opsins. I then use these cell-specific gene editing approaches to target MORs in excitatory or inhibitory RVM neurons, demonstrating that opioid receptor signaling in these populations works in concert to moderate the early phase of neuropathic pain. Finally, I demonstrate that activation of either inhibitory or excitatory RVM neurons alone reduces reflexive pain responses at baseline, but chemogenetic activation of excitatory RVM neurons exacerbates hyperalgesia in the setting of neuropathic pain. Understanding how opioid signaling in the RVM produces analgesia could lead to the development of new therapies for chronic pain that engage endogenous pain control mechanisms.
Graduate publications
Moffa JC, Bland IN, Tooley JR, Kalyanaraman V, Heitmeier M, Creed MC, Copits BA. 2024 Cell specific single viral vector CRISPR/Cas9 editing and genetically encoded tool delivery in the central and peripheral nervous systems. eNeuro, 11(7):ENEURO.0438-23.2024.