ArticleMolecular psychiatry2023
Development of opioid-induced hyperalgesia depends on reactive astrocytes controlled by Wnt5a signaling.
Article in Molecular psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- The Wnt5a-PKCδ-GluA1 axis controls synapse-specific plasticity in HIV-1 gp120-induced pain pathogenesis.Brain : a journal of neurology · 2026Article
- Dual CCR2/CCR5 Antagonism with Cenicriviroc Alleviates Nerve Injury-Induced Hypersensitivity and Prevents Morphine Tolerancevia Modulation of Neuroimmune Signaling.Cellular and molecular neurobiology · 2026Article
- Water channel changes in astrocytes associated with buprenorphine administration in a rat model of diffuse traumatic brain injury.Research square · 2026Article
- Multifaceted Astrocyte-Neuron Cross-Talk in Neuropathic Pain: Potential Mechanisms and Functional Implications.Journal of pain research · 2026Review
- Oral Ketamine for Chronic Pain: Towards an Evidence-Based Dosing Regimen.Journal of pain research · 2026Review
- Influence of qNOX-guided remifentanil titration on intraoperative dosing and postoperative pain in total knee arthroplasty: a pilot randomized trial.Journal of anesthesia, analgesia and critical care · 2025Article
- Identification of a reactive astrocyte subpopulation during HIV-associated pain pathogenesis in mouse models.Nature communications · 2025Article
- Neuroplasticity-related genes correlate with individual differences in distinct phases of oxycodone self-administration in male rats.Neuropharmacology · 2024Article
- Sustained morphine exposure alters spinal NMDA receptor and astrocyte expression and exacerbates chronic pain behavior in female rats.Pain reports · 2024Article
- Review
- Review
- Pathogenic mechanisms of human immunodeficiency virus (HIV)-associated pain.Molecular psychiatry · 2023Review
- P2X4 signalling contributes to hyperactivity but not pain sensitization comorbidity in a mouse model of attention deficit/hyperactivity disorder.Frontiers in pharmacology · 2023Article
- Reactive astrocytes in pain neural circuit pathogenesis.Current opinion in neurobiology · 2022Review
- Epigenetic regulation in opioid induced hyperalgesia.Neurobiology of pain (Cambridge, Mass.)Review
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 2 countries.
Funding
Abstract
Opioids are the frontline analgesics for managing various types of pain. Paradoxically, repeated use of opioid analgesics may cause an exacerbated pain state known as opioid-induced hyperalgesia (OIH), which significantly contributes to dose escalation and consequently opioid overdose. Neuronal malplasticity in pain circuits has been the predominant proposed mechanism of OIH expression. Although glial cells are known to become reactive in OIH animal models, their biological contribution to OIH remains to be defined and their activation mechanism remains to be elucidated. Here, we show that reactive astrocytes (a.k.a. astrogliosis) are critical for OIH development in both male and female mice. Genetic reduction of astrogliosis inhibited the expression of OIH and morphine-induced neural circuit polarization (NCP) in the spinal dorsal horn (SDH). We found that Wnt5a is a neuron-to-astrocyte signal that is required for morphine-induced astrogliosis. Conditional knock-out of Wnt5a in neurons or its co-receptor ROR2 in astrocytes blocked not only morphine-induced astrogliosis but also OIH and NCP. Furthermore, we showed that the Wnt5a-ROR2 signaling-dependent astrogliosis contributes to OIH via inflammasome-regulated IL-1β. Our results reveal an important role of morphine-induced astrogliosis in OIH pathogenesis and elucidate a neuron-to-astrocyte intercellular Wnt signaling pathway that controls the astrogliosis.
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