Journal
BRAIN
Volume 145, Issue 7, Pages 2293-2300Publisher
OXFORD UNIV PRESS
DOI: 10.1093/brain/awac085
Keywords
noradrenaline; locus coeruleus; descending modulation; diffuse noxious inhibitory controls; spinal wide dynamic range neurons
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Funding
- Academy of Medical Sciences, Springboard grant [SBF004\1064]
- National Centre for the Replacement, Refinement and Reduction of Animals in Research studentship [NC/T002115/1]
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This study investigates the relationship between brain-spine pathways that project from the brain to the spinal cord and shows that their ability to inhibit pain depends on their connectivity, revealing a separable function for parallel brain-spine circuits.
Brainstem to spinal cord noradrenergic pathways include a locus coeruleus origin projection and diffuse noxious inhibitory controls. While both pathways are traditionally viewed as exerting an inhibitory effect on spinal neuronal activity, the locus coeruleus was previously shown to have a facilitatory influence on thermal nocioception according to the subpopulation of coerulean neurons activated. Coupled with knowledge of its functional modular organisation and the fact that diffuse noxious inhibitory controls are not expressed in varied animal models of chronicity, we hypothesized a regulatory role for the locus coeruleus on non-coerulean, discrete noradrenergic cell group(s). We implemented locus coeruleus targeting strategies by microinjecting canine adenovirus encoding for channelrhodopsin-2 under a noradrenaline-specific promoter in the spinal cord (retrogradely labelling a coeruleospinal module) or the locus coeruleus itself (labelling the entire coerulean module). Coeruleospinal module optoactivation abolished diffuse noxious inhibitory controls (two-way ANOVA, P < 0.0001), which were still expressed following locus coeruleus neuronal ablation. We propose that the cerulean system interacts with, but does not directly govern, diffuse noxious inhibitory controls. This mechanism may underlie the role of the locus coeruleus as a 'chronic pain generator'. Pinpointing the functionality of discrete top-down pathways is crucial for understanding sensorimotor modulation in health and disease. Nerve pathways project from the brain to the spinal cord to influence pain perception. Kucharczyk et al. investigate the relationship between two such pathways and show that their ability to inhibit pain depends on their connectivity, thus revealing a separable function for parallel brain-spine circuits.
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