The ‘in’s and out’s’ of descending pain modulation from the rostral ventromedial medulla

The rostral ventromedial medulla (RVM) is the key output node of the descending pain-modulating system.Intrinsic and extrinsic factors contribute to the pain experience by influencing the activity of two functional types of RVM neurons, OFF-cells and ON-cells, which respectively exert inhibitory and...

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Veröffentlicht in:Trends in neurosciences (Regular ed.) 2024-06, Vol.47 (6), p.447-460
Hauptverfasser: De Preter, Caitlynn C., Heinricher, Mary M.
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Sprache:eng
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Zusammenfassung:The rostral ventromedial medulla (RVM) is the key output node of the descending pain-modulating system.Intrinsic and extrinsic factors contribute to the pain experience by influencing the activity of two functional types of RVM neurons, OFF-cells and ON-cells, which respectively exert inhibitory and facilitatory control over nociceptive transmission and pain.Dysfunction in descending control, which alters the distinct inhibitory and facilitatory outputs of RVM, contributes to persistent pain states.Characterizing the function(s) of genetically defined RVM populations has been challenging and conflicting results have emerged, stressing the need for rigorous interpretation of experiments based on candidate molecular markers.Further investigation of interactions within and between functional RVM populations are a critical next step in improving our understanding of descending control of pain. The descending-pain modulating circuit controls the experience of pain by modulating transmission of sensory signals through the dorsal horn. This circuit’s key output node, the rostral ventromedial medulla (RVM), integrates ‘top-down’ and ‘bottom-up’ inputs that regulate functionally defined RVM cell types, ‘OFF-cells’ and ‘ON-cells’, which respectively suppress or facilitate pain-related sensory processing. While recent advances have sought molecular definition of RVM cell types, conflicting behavioral findings highlight challenges involved in aligning functional and molecularly defined types. This review summarizes current understanding, derived primarily from rodent studies but with corroborating evidence from human imaging, of the role of RVM populations in pain modulation and persistent pain states and explores recent advances outlining inputs to, and outputs from, RVM pain-modulating neurons. The descending-pain modulating circuit controls the experience of pain by modulating transmission of sensory signals through the dorsal horn. This circuit’s key output node, the rostral ventromedial medulla (RVM), integrates ‘top-down’ and ‘bottom-up’ inputs that regulate functionally defined RVM cell types, ‘OFF-cells’ and ‘ON-cells’, which respectively suppress or facilitate pain-related sensory processing. While recent advances have sought molecular definition of RVM cell types, conflicting behavioral findings highlight challenges involved in aligning functional and molecularly defined types. This review summarizes current understanding, derived primarily from rodent studi
ISSN:0166-2236
1878-108X
1878-108X
DOI:10.1016/j.tins.2024.04.006