ArticlePain2025
Decreased KCC2 expression in the human spinal dorsal horn associated with chronic pain and long-term opioid use.
Article in Pain, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed.
- An All-Optical Approach to Probe Chloride Transport with a Bright ChlorON.bioRxiv : the preprint server for biology · 2026Article
- Processing and sectioning of organ donor spinal cord tissue for electrophysiology on acute human spinal cord slices.Brain communications · 2026Article
- The Informational Blackout chronic pain and fatigue as rational outputs of a brain operating on degraded biological signals.Frontiers in pain research (Lausanne, Switzerland) · 2026Article
- Mechanical cues as immunomodulators in neuroinflammation-driven spinal sensitization: analgesic mechanisms and therapeutic strategies.Frontiers in immunology · 2026Review
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Corrections and comments
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Authors and funding
19 authors.
Funding
Abstract
abstractLoss of GABAergic and glycinergic inhibitory efficacy in the spinal dorsal horn is associated with neuropathic pain and opioid-induced hyperalgesia in rodent models. Downregulation of the KCC2 chloride extrusion transporter is a key mechanism underlying this decreased inhibitory efficacy, but to-date there is no evidence supporting or opposing this hypothesis in humans. Here, we demonstrate that KCC2 expression is decreased in superficial dorsal horn neurons of organ donors who died with a documented history of pain, or of long-term opioid use. We show profoundly decreased KCC2 dorsal horn membrane expression in a primary cohort associated with either chronic pain or opioid use, and in a replication cohort of mixed chronic pain and opioid use history. These results show that decreased dorsal horn inhibitory efficacy likely promotes chronic pain in humans and support the development of therapeutics augmenting KCC2 function as a treatment for chronic pain and opioid use disorders.
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What OpenQuestion holds
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.