ArticleScience advances2022
Switch of serotonergic descending inhibition into facilitation by a spinal chloride imbalance in neuropathic pain.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The trial behind it
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Who cites it
18 citing papers in PubMed.
- Gabapentinoids-duloxetine combination therapy for chronic pain: A mechanism oriented rational to bridge theoretical knowledge and real life setting.British journal of clinical pharmacology · 2026Review
- Molecular and Cellular Mechanisms of Spinal Cord Stimulation: Linking Dorsal Horn Circuits, Glia, and ECAP-Guided Therapy.International journal of molecular sciences · 2026Review
- Review
- A Freshwater Pearl Mussel Polysaccharide Alleviates Inflammatory Pain by Targeting Peripheral Cytokines and Spinal Astroglial NLRP3/GFAP Responses.Food science & nutrition · 2026Article
- Chronic stress increases the susceptibility to chronic vulvar pain following acute vulvar inflammation in a preclinical model of vulvodynia.Molecular brain · 2026Article
- The role of gut microbiota in neuropathic pain: insights into immune mechanisms.The journal of headache and pain · 2025Review
- Targeting the hypothalamic a11 nucleus to treat parkinsonian-like nociceptive impairments.NPJ Parkinson's disease · 2025Article
- Pain Perception and Modulation: Fundamental Neurobiology and Recent Advances.The European journal of neuroscience · 2025Review
- Nociceptor-localized KCC2 suppresses brachial plexus avulsion-induced neuropathic pain and related central sensitization.Cell & bioscience · 2025Article
- Brainstem serotonin amplifies nociceptive transmission in a mouse model of Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Article
- Modulating Neural Circuits of Pain in Preclinical Models: Recent Insights for Future Therapeutics.Cells · 2024Review
- Analgesic effects of oral Yokukansan on acute postoperative pain and involvement of the serotonin nervous system: a mouse model study.BMC complementary medicine and therapies · 2024Article
- Development of KCC2 therapeutics to treat neurological disorders.Frontiers in molecular neuroscience · 2024Article
- Article
- Microglial P2X4 receptors are essential for spinal neurons hyperexcitability and tactile allodynia in male and female neuropathic mice.iScience · 2023Article
- Neuropathic pain; what we know and what we should do about it.Frontiers in pain research (Lausanne, Switzerland) · 2023Review
- EA participates in pain transition through regulating KCC2 expression by BDNF-TrkB in the spinal cord dorsal horn of male rats.Neurobiology of pain (Cambridge, Mass.)Article
Corrections and comments
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Authors and funding
17 authors.
Funding
No grant is acknowledged in the PubMed record.
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 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.