ABY, Franck; LORENZO, Louis-Etienne; GRIVET, Zoe; BOUALI-BENAZZOUZ, Rabia; MARTIN, Hugo; VALERIO, Stephane; WHITESTONE, Sara; ISABEL, Dominique; IDI, Walid; BOUCHATTA, Otmane; DE DEURWAERDERE, Philippe; GODIN, Antoine G.; HERRY, Cyril; FIORAMONTI, Xavier; LANDRY, Marc; DE KONINCK, Yves; FOSSAT, Pascal

doi:10.1126/sciadv.abo0689

ABY, Franck
Institut des Maladies Neurodégénératives [Bordeaux] [IMN]

LORENZO, Louis-Etienne

GRIVET, Zoe

Institut des Maladies Neurodégénératives [Bordeaux] [IMN]
Université de Bordeaux [UB]

Idioma

Article de revue

Este ítem está publicado en

Science Advances. 2022-07-29, vol. 8, n° 30

Resumen en inglés

Descending control from the brain to the spinal cord shapes our pain experience, ranging from powerful analgesia to extreme sensitivity. Increasing evidence from both preclinical and clinical studies points to an imbalance toward descending facilitation as a substrate of pathological pain, but the underlying mechanisms remain unknown. We used an optogenetic approach to manipulate serotonin (5-HT) neurons of the nucleus raphe magnus that project to the dorsal horn of the spinal cord. We found that 5-HT neurons exert an analgesic action in naïve mice that becomes proalgesic in an experimental model of neuropathic pain. We show that spinal KCC2 hypofunction turns this descending inhibitory control into paradoxical facilitation; KCC2 enhancers restored 5-HT–mediated descending inhibition and analgesia. Last, combining selective serotonin reuptake inhibitors (SSRIs) with a KCC2 enhancer yields effective analgesia against nerve injury–induced pain hypersensitivity. This uncovers a previously unidentified therapeutic path for SSRIs against neuropathic pain. Copyright © 2022 The Authors.< Leer menos

Palabras clave en inglés

Chlorine Compounds

Health

Clinical Study

Descending Inhibitions

Experimental Modelling

Nerve Injuries

Neuropathic Pain

Optogenetics

Preclinical Studies

Selective Serotonin Re-Uptake Inhibitors

Spinal-Cord

Mammals

URI

https://oskar-bordeaux.fr/handle/20.500.12278/170445

DOI

http://dx.doi.org/10.1126/sciadv.abo0689

Proyecto ANR

Circuits neuronaux de l'analgésie conditionnée
Bordeaux Region Aquitaine Initiative for Neuroscience - ANR-10-LABX-0043

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Switch of serotonergic descending inhibition into facilitation by a spinal chloride imbalance in neuropathic pain

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Switch of serotonergic descending inhibition into facilitation by a spinal chloride imbalance in neuropathic pain

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Palabras clave en inglés

URI

DOI

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Centros de investigación