Pain Circuits
Persistent pain remains a major clinical problem due in large part to an incomplete understanding of its underlying neuronal circuits and mechanisms. Our work in this area has focused on identifying the circuitry required for mechanical allodynia, a condition in which touch becomes painful in the setting of injury (Peirs et al, Neuron, 2015, Seal and Peirs, Science 2016) as well as circuitry that conveys spontaneous pain using a combination of chemogenetics, viral tracing, in vivo calcium imaging, electrophysiology and behavior.
A second area of import is the study of cholecystokinin, the most common neuropeptide in the mammalian nervous system, which has been implicated in mechanical allodynia as well as in antagonizing the analgesic effects of morphine and in promoting morphine tolerance. We have generated conditional CCK and CCK B receptor knockout mice to dissect the neural circuitry underlying these therapeutically relevant signaling mechanisms. We will use the information and tools that we have developed to intervene in the neural circuitry for therapeutic purposes.
For this goal, we have embarked on a third area of study focused on the cellular and molecular organization of the rhesus macaque dorsal horn using single cell sequencing, bioinformatics and RNAScope to compare to human and mouse dorsal horn. Together, our work will provide important new insights into how the mammalian nervous system processes persistent pain and will lead to much needed new treatment strategies.