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The primary mission of my laboratory is to elucidate the mechanisms that underlie pain perception and its modulation by opioids. We investigate the sensory, affective, and cognitive dimensions of pain experience, and both the analgesic and side effects of opioids, including addiction and respiratory depression. Our experimental strategies use a variety of methods that range from molecular to systems neuroscience approaches, including mouse genetics, nucleic acid and protein molecular and cellular biology, fluorescence and electronic microscopy, neuroanatomical tracing of circuits with viruses, electrophysiology, opto- and chemo-genetic manipulation of neural activity, and imaging of neural dynamics in freely behaving mice. With these techniques, we determine the function in pain and opioid neuromodulation of a variety of cell types and molecules throughout peripheral nervous system, spinal cord, and brain. Our long-term objective is to build on these discoveries to develop innovative therapeutics to treat pain effectively and safely and to alleviate opioid side effects.
I have been studying the neurobiology of pain and opioids for the past 22 years. I was trained as a molecular biologist and pharmacologist during which time I generated knockin mice that express opioid receptors tagged with fluorophores or bearing a conditional allele (Cre/loxP system) and revealed the contribution of drug-induced G protein-coupled receptor internalization to tolerance in vivo (Scherrer et al., Proc Natl Acad Sci U S A, 2006; Chu Sin Chung, Biol Psychiatry, 2015). I then trained in the neural circuits of pain, establishing the somatosensory modality-specific distribution and function of vesicular glutamate transporter and opioid receptor types using neuroanatomical techniques, electrophysiology and mouse models of pain (Scherrer et al., Cell, 2009; Scherrer et al., PNAS, 2010; Basbaum et al., Cell, 2009). I joined the Neurosciences Institute and the Department of Anesthesiology at Stanford University in 2012 as an Assistant Professor. In 2019, I moved my laboratory to the University of North Carolina at Chapel Hill where I continue my research on pain and opioids as an Associate Professor in the Department of Cell Biology and Physiology and Neuroscience Center.
The following studies exemplify the activity of my laboratory and our approach to pain and opioid science. We used slice electrophysiology and confocal microscopy to reveal the divergent trafficking of opioid receptor subtypes in CNS neurons of the pain circuitry (Wang et al., Neuron, 2018). We identified the critical function of mu opioid receptors in nociceptors in the development of opioid tolerance and hyperalgesia using RNA sequencing and conditional gene ablation (Corder et al., Nat Med, 2017). My lab participated in a collaborative project for which we determined the analgesic efficacy of a novel mu opioid receptor agonist, PZM21, against the sensory and affective components of pain (Manglik et al., Nature, 2016). We developed a novel optogenetic method for manipulating the activity of spinal neurons in freely moving mice (Christensen et al., Cell Reports, 2016). We demonstrated that the delta opioid receptor (DOP) controls the activity of cutaneous mechanosensory neurons responsible for neuropathic pain (Bardoni et al., Neuron, 2014). Using neural circuit tracing, we uncovered a pathway by which brainstem GABAergic neurons control spinal enkephalinergic neurons to tune mechanical pain thresholds (François et al., Neuron, 2017). Finally, by imaging neural dynamics in freely moving mice, we identified a neural ensemble that encodes the unpleasant quality of pain (Corder et al., Science, 2019).