Switch of serotonergic descending inhibition into facilitation by a spinal chloride imbalance in neuropathic pain
Language
EN
Article de revue
This item was published in
Science Advances. 2022-07-29, vol. 8, n° 30
English Abstract
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 ...Read more >
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.Read less <
English Keywords
Chlorine Compounds
Health
Clinical Study
Descending Inhibitions
Experimental Modelling
Nerve Injuries
Neuropathic Pain
Optogenetics
Preclinical Studies
Selective Serotonin Re-Uptake Inhibitors
Spinal-Cord
Mammals
ANR Project
Circuits neuronaux de l'analgésie conditionnée
Bordeaux Region Aquitaine Initiative for Neuroscience - ANR-10-LABX-0043
Bordeaux Region Aquitaine Initiative for Neuroscience - ANR-10-LABX-0043