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Functional Connectivity of Prelimic Prefrontal Cortex and Rostral Ventromedial Medulla for Descending Pain Modulation
Author(s) -
Smith Angela,
Flohrschutz Austin,
Riegel Arthur,
Largent-Milnes Tally,
Vanderah Todd
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.03633
Subject(s) - rostral ventromedial medulla , neuroscience , prefrontal cortex , periaqueductal gray , psychology , nociception , hyperalgesia , medicine , receptor , central nervous system , midbrain , cognition
Chronic pain is a health condition that can seriously impact quality of life. To develop better treatments for chronic pain, a better understanding of the mechanisms behind pain perception is needed. Current models of descending pain modulation show the prelimbic prefrontal cortex (plPFC; area 32V) synapsing onto cells within the periaqueductal grey (PAG) which then synapses onto the rostral ventromedial medulla (RVM). The RVM contains ‘on’ and ‘off’ cells which respond to pain stimuli by respectively activating or inhibiting pain perception. We aim to functionally characterize a hypothesized direct projection from the plPFC to the RVM first described in 1997. Anterograde tracing was performed in the plPFC to determine the anatomical connectivity of the two regions. Similarly, we transfected the plPFC with hM4Dq DREADDs fused with mCherry under the control of CaMKIIa promoters to label glutamatergic Layer 5 projection neurons and determine functional connectivity of the purported circuit in animals with a spared nerve injury (SNI). These receptors are inert unless acted on by a designer drug, such as CNO. We used reverse microdialysis to locally deliver CNO into the RVM and activate DREADDs on neurons with direct projections from the plPFC while collecting released neurotransmitter and performing reflexive pain behaviors assays. This strategy allowed for avoidance of systemic/off target activation of plPFC neurons projecting to a different CNS region. Anatomical and microanalysis pilot data indicate a direct connection from plPFC to the RVM. Support or Funding Information Funding provided by the University of Arizona Department of Medicinal Pharmacology, University of Arizona Undergraduate Biological Research Program, and the ASPET Summer Undergraduate Research Fellows Program.