ArticlePain2020
Wnt signaling contributes to withdrawal symptoms from opioid receptor activation induced by morphine exposure or chronic inflammation.
Article in Pain, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 35 citations in OpenAlex.
- Sex Differences in Pain Contagion Determined by the Balance of Oxytocin and Corticosterone in the Anterior Cingulate Cortex in Rodents.Neuroscience bulletin · 2025Article
- Morphine-induced hyperalgesia impacts small extracellular vesicle microRNA composition and function.The Journal of pharmacology and experimental therapeutics · 2025Article
- Morphine-induced hyperalgesia impacts small extracellular vesicle miRNA composition and function.bioRxiv : the preprint server for biology · 2024Article
- [D-Ala2, D-Leu5]-enkephalin (DADLE) provides protection against myocardial ischemia reperfusion injury by inhibiting Wnt/β-Catenin pathway.BMC cardiovascular disorders · 2024Article
- YAP/TAZ: Molecular pathway and disease therapy.MedComm · 2023Review
- Profiling neuronal methylome and hydroxymethylome of opioid use disorder in the human orbitofrontal cortex.Nature communications · 2023Article
- Article
- DKK3 ameliorates neuropathic pain via inhibiting ASK-1/JNK/p-38-mediated microglia polarization and neuroinflammation.Journal of neuroinflammation · 2022Article
- Physiological dependence to mitragynine indicated by a rapid cross-dependence procedure with heroin-dependent mice.Psychopharmacology · 2022Article
- Estrogen receptor alpha and NFATc1 bind to a bone mineral density-associated SNP to repress WNT5B in osteoblasts.American journal of human genetics · 2022Article
- 5-HTFrontiers in pharmacology · 2022Article
- CpH methylome analysis in human cortical neurons identifies novel gene pathways and drug targets for opioid use disorder.Frontiers in psychiatry · 2022Article
- WNT5B in Physiology and Disease.Frontiers in cell and developmental biology · 2021Review
- Differential DNA methylation in Black and White individuals with chronic low back pain enrich different genomic pathways.Neurobiology of pain (Cambridge, Mass.)Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Preventing and treating opioid dependence and withdrawal is a major clinical challenge, and the underlying mechanisms of opioid dependence and withdrawal remain elusive. We hypothesized that prolonged morphine exposure or chronic inflammation-induced μ-opioid receptor activity serves as a severe stress that elicits neuronal alterations and recapitulates events during development. Here, we report that Wnt signaling, which is important in developmental processes of the nervous system, plays a critical role in withdrawal symptoms from opioid receptor activation in mice. Repeated exposures of morphine or peripheral inflammation produced by intraplantar injection of complete Freund's adjuvant significantly increase the expression of Wnt5b in the primary sensory neurons in dorsal root ganglion (DRG). Accumulated Wnt5b in DRG neurons quickly transmits to the spinal cord dorsal horn (DH) after naloxone treatment. In the DH, Wnt5b, acts through the atypical Wnt-Ryk receptor and alternative Wnt-YAP/TAZ signaling pathways, contributing to the naloxone-precipitated opioid withdrawal-like behavioral symptoms and hyperalgesia. Inhibition of Wnt synthesis and blockage of Wnt signaling pathways greatly suppress the behavioral and neurochemical alterations after naloxone-precipitated withdrawal. These findings reveal a critical mechanism underlying naloxone-precipitated opioid withdrawal, suggesting that targeting Wnt5b synthesis in DRG neurons and Wnt signaling in DH may be an effective approach for prevention and treatment of opioid withdrawal syndromes, as well as the transition from acute to chronic 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.