Emma Hovanec

School: The University of Chicago

Major: Biological Sciences

DOI: https://doi.org/10.21985/n2-qyyv-m648

Emma Hovanec graduated from the University of Chicago in June 2020 with a Bachelor of Science in Neuroscience. As an undergraduate, she spent 2 years in the McGehee lab researching questions of addiction and pain. She is particularly interested in the modulation of descending pain control and perception and wrote her senior thesis on the role and expression of a7 nicotinic receptors in this system. Other academic interests include the neuroendocrinology of secondary-sex characteristics, social determinants of health and health, and inequality in the American healthcare system. Outside of the classroom, Emma plays rugby, reads fiction, and advocates for reproductive justice and healthcare access for all.

Alpha7 Nicotinic Acetylcholine Receptor Modulation of Descending Pain Control Pathways

Abstract

The ventrolateral Periaqueductal Gray (vlPAG) is a midbrain structure in the descending pathway that modulates chronic and acute pain. vlPAG plays a critical role in pain transmission via projections to the Rostral Ventromedial Medulla (RVM), which projects to spinal cord. Existing research demonstrates that vlPAG neurons express α7-nicotinic acetylcholine receptors (α7-nAChRs), and activation of these receptors produces anti-nociception with efficacy similar to opioids. Recent studies show that chemogenetic excitation of glutamatergic neurons or inhibition of GABAergic neurons in vlPAG produce anti-nociception, however, the role of α7-nAChRs in this effect remains uncertain. The neurotransmitter phenotype of α7-expressing vlPAG neurons is not characterized, and it is unclear if α7-nAChRs are expressed predominantly on local interneurons or vlPAG-RVM projection neurons. To address these questions, we confirmed that α7-nAChR agonist activation produces anti-nociception in mice. We conducted mRNA and protein labeling experiments and identified that α7-nAChRs are predominantly expressed on GABAergic neurons. We also found that α7-expressing GABAergic neurons co-express u-opioid receptors (MORs). Conventionally, α7-nAChRs are excitatory while MORs are inhibitory. In light of the high degree of overlapping expression, we hypothesize that α7-nAChRs inhibit neuronal activity to induce anti-nociception. We assayed c-fos expression in vlPAG following formalin administration and found that α7-nAChR neurons are active in a nociceptive state. Together, this data supports our hypothesis that α7-expressing GABAergic interneurons are active during nociception and inactivate via α7-nAChR activation to disinhibit glutamatergic projections to RVM and relieve pain. These findings signify the ongoing relevance of α7-nAChRs as potential non-opioid therapeutic targets for pain relief.