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Authors & Affiliations
Carl Ashworth, Caitlynn De Preter, Melissa Martenson, Zhigang Shi, Mary Heinricher, Flavia Mancini
Abstract
Chronic pain is a serious clinical and scientific problem, affecting 1 in 5 people worldwide, yet its mechanisms and ways to treat it remain poorly understood. Pain is modulated by endogenous pain modulatory pathways that connect the brain to the spinal cord, up- and down-regulating the transmission of nociceptive information. The most important region when such modulation occurs is the Rostral Ventromedial Medulla (Fields et al., 1983; Chen and Heinricher, 2022). Despite extensive work characterising the responses of RVM cells during pharmacological interventions, little is currently known about their population behaviour and connectivity within the RVM (De Preter and Heinricher, 2024).
We analysed the population dynamics of RVM cells, from recordings in lightly anaesthetised rats, both at rest and in response to noxious stimuli. We found evidence for strongly connected subpopulations of bi-stable RVM cells (OFF and ON cells), alongside periodic population fluctuations with a period of 5 minutes present in these cells, across animals, trials, and locations within the RVM. Figure 1 shows the frequency plots and strongly correlated activity observed. This frequency did not correlate with heart rate, despite previous work showing evidence for MAP fluctuations correlated with RVM activity (Leung and Mason, 1996; El Bitar, Pollin and Le Bars, 2014). This research suggests that although the RVM does not show somatotopic organisation, there may be subgroups of cells which function as tightly coupled networks within the global population behaviour. It also suggests several possible connectivity structures for the RVM, opening avenues for further research into the anatomical and functional connectivity of this region.