A critical brainstem relay for mediation of diffuse noxious inhibitory controls.
descending pain modulatory system (DPMS)
diffuse noxious inhibitory controls (DNIC)
in vivo electrophysiology
noradrenaline
optogenetics
pain inhibition
wide dynamic range neurons
Journal
Brain : a journal of neurology
ISSN: 1460-2156
Titre abrégé: Brain
Pays: England
ID NLM: 0372537
Informations de publication
Date de publication:
01 06 2023
01 06 2023
Historique:
received:
08
08
2022
revised:
06
11
2022
accepted:
05
12
2022
medline:
2
6
2023
pubmed:
11
1
2023
entrez:
10
1
2023
Statut:
ppublish
Résumé
The CNS houses naturally occurring pathways that project from the brain to modulate spinal neuronal activity. The noradrenergic locus coeruleus (the A6 nucleus) originates such a descending control whose influence on pain modulation encompasses an interaction with a spinally projecting non-cerulean noradrenergic cell group. Hypothesizing the origin of an endogenous pain inhibitory pathway, our aim was to identify this cell group. A5 and A7 noradrenergic nuclei also spinally project. We probed their activity using an array of optogenetic manipulation techniques during in vivo electrophysiological experimentation. Interestingly, noxious stimulus evoked spinal neuronal firing was decreased upon opto-activation of A5 neurons (two-way ANOVA with Tukey post hoc, P < 0.0001). Hypothesizing that this may reflect activity in the noradrenergic diffuse noxious inhibitory control circuit, itself activated upon application of a conditioning stimulus, we opto-inhibited A5 neurons with concurrent conditioning stimulus application. Surprisingly, no spinal neuronal inhibition was observed; activity in the diffuse noxious inhibitory control circuit was abolished (two-way ANOVA, P < 0.0001). We propose that the A5 nucleus is a critical relay nucleus for mediation of diffuse noxious inhibitory controls. Given the plasticity of diffuse noxious inhibitory controls in disease, and its back and forward clinical translation, our data reveal a potential therapeutic target.
Identifiants
pubmed: 36625030
pii: 6980486
doi: 10.1093/brain/awad002
pmc: PMC10232242
doi:
Substances chimiques
Norepinephrine
X4W3ENH1CV
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2259-2267Subventions
Organisme : Medical Research Council
ID : MR/W004739/1
Pays : United Kingdom
Organisme : National Centre for the Replacement, Refinement and Reduction of Animals in Research
ID : NC/T002115/1
Pays : United Kingdom
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.
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