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MAPPING MEDULLARY MECHANISMS: PAIN, PYREXIA, AND PARACETAMOL
Parameswaran Valiathanand 1 co-author
Karolinska Institutet
FENS Forum 2026 (2026)
Barcelona, Spain
Board PS01-07AM-451
Presentation
Date TBA
Board: PS01-07AM-451
Event Information
Poster Board
PS01-07AM-451
Poster
View posterAbstract
The rostral ventromedial medulla (RVM) is a key regulator of pain and associated behaviors in rodents and humans. Since the 1980s, research has established the RVM as a primary effector of central pain modulation via the descending pathway (Fields et al., 1983). Classic electrophysiological studies identified three distinct neuronal populations in the RVM—"ON cells," "OFF cells," and "Neutral cells"—defined by their responses to noxious stimuli: ON cells increase activity, OFF cells decrease activity, and Neutral cells remain unresponsive (Heinricher et al., 1987). However, traditional recording methods are limited in their ability to track these cells over extended periods, establish causal roles in pain perception, or capture population-level dynamics.
To address these limitations, we developed a novel orthogonal dual c-Fos tagging technique using Capturing Activated Neuronal Ensembles (CANE). This approach allows us to isolate specific medullary ensembles, independently modulate their activity, and simultaneously monitor calcium dynamics during behavior. We applied this framework to characterize the systems-level impact of paracetamol (acetaminophen) on pain-responsive ON cells and morphine-sensitive OFF cells. Combined with circuit-level dissection, our results identify novel parallel pathways within the RVM that are necessary for the antinociceptive and antipyretic actions of paracetamol.
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