ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2017
Sex Differences in Microglia Activity within the Periaqueductal Gray of the Rat: A Potential Mechanism Driving the Dimorphic Effects of Morphine.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers, 1 of them a synthesis that pooled it.
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
109 citing papers in PubMed, 1 synthesis or guideline pooled it, 171 citations in OpenAlex.
- Sexually Dimorphic Neuroimmune Pathways in Chronic Pain: A Comprehensive Systematic Review of Cellular and Molecular Mechanisms.Biomolecules · 2026Pooled it
- Impact of sex differences on microglial function in Alzheimer's disease.Alzheimer's research & therapy · 2026Review
- The actions of morphine on microglia and the underlying effects on associated adverse effects.Psychopharmacology · 2026Review
- GWAS of extended prescription analgesic use identifies genetic loci in chronic pain.Nature communications · 2026Article
- Gonadal and sex chromosomal contributions to sex differences in mammalian brain organization.bioRxiv : the preprint server for biology · 2026Article
- Brain nitric oxide and inflammation in chronic intermittent hypoxia: Contributors to cognitive impairment and hypertension.Brain, behavior, & immunity - health · 2025Review
- Microglia/macrophage-specific deletion of TLR-4 protects against neural effects of diet-induced obesity in a sexually dimorphic manner.Journal of neuroinflammation · 2025Article
- Astrocytes and Astrocyte-Derived Extracellular Conduits in Opiate-Mediated Neurological Disorders.Cells · 2025Review
- Therapeutic Potential of Edaravone for Neuroprotection Following Global Cerebral Hypoxia.International journal of molecular sciences · 2025Article
- Peroxisome, neuropeptide, and inflammation signaling pathways uniquely impacted by opioid exposure in the hypothalamus of males and females.Molecular and cellular neurosciences · 2025Article
- Altered Microglial Plasticity in the Periaqueductal Grey of Pre-Symptomatic Mecp2-Heterozygous Mice Following Early-Life Stress.Neuromolecular medicine · 2025Article
- Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer's disease.Immunity · 2025Article
- Increased LPS-induced fever and sickness behavior in adult male and female rats perinatally exposed to morphine.Brain, behavior, and immunity · 2025Article
- Sex chromosomes and sex hormones differently shape microglial properties during normal physiological conditions in the adult mouse hippocampus.Journal of neuroinflammation · 2025Article
- Recent Advances in the Mechanisms of Postoperative Neurocognitive Dysfunction: A Narrative Review.Biomedicines · 2025Review
- The role of gonadal hormones in regulating opioid antinociception.Annals of medicine · 2024Review
- Targeting exosomal double-stranded RNA-TLR3 signaling pathway attenuates morphine tolerance and hyperalgesia.Cell reports. Medicine · 2024Article
- Self-regulated analgesia in males but not females is mediated by endogenous opioids.PNAS nexus · 2024Article
- Examining the effects of the HIV-1 protein Tat and morphine on antiretroviral accumulation and distribution within the brain.Clinical and translational science · 2024Article
- Brain-derived neurotrophic factor contributes to activity-induced muscle pain in male but not female mice.Brain, behavior, and immunity · 2024Article
49 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Although morphine remains the primary drug prescribed for alleviation of severe or persistent pain, both preclinical and clinical studies have shown that females require two to three times more morphine than males to produce comparable levels of analgesia. In addition to binding to the neuronal μ-opioid receptor, morphine binds to the innate immune receptor toll-like receptor 4 (TLR4) localized primarily on microglia. Morphine action at TLR4 initiates a neuroinflammatory response that directly opposes the analgesic effects of morphine. Here, we test the hypothesis that the attenuated response to morphine observed in females is the result of increased microglia activation in the periaqueductal gray (PAG), a central locus mediating the antinociceptive effects of morphine. We report that, whereas no overall sex differences in the density of microglia were noted within the PAG of male or female rats, microglia exhibited a more "activated" phenotype in females at baseline, with the degree of activation a significant predictor of morphine half-maximal antinociceptive dose (ED
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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.