ArticleThe journal of pain2013
Persistent peripheral inflammation attenuates morphine-induced periaqueductal gray glial cell activation and analgesic tolerance in the male rat.
Article in The journal of pain, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 62 citations in OpenAlex.
- Integrated quantitative proteomics reveals stress-associated network remodeling induced by mitragynine in RSC96 Schwann cells.Archives of toxicology · 2026Article
- NLRP3 inflammasome: a key driver of neuroinflammation and a novel therapeutic target for neuropathic pain.Anesthesia and pain medicine · 2025Review
- Increased LPS-induced fever and sickness behavior in adult male and female rats perinatally exposed to morphine.Brain, behavior, and immunity · 2025Article
- Repeated Administrations of Polyphenolic Extracts Prevent Chronic Reflexive and Non-Reflexive Neuropathic Pain Responses by Modulating Gliosis and CCL2-CCR2/CX3CL1-CX3CR1 Signaling in Spinal Cord-Injured Female Mice.International journal of molecular sciences · 2025Article
- Low-intensity sciatic nerve-stretch injury increases nociception, anxiety-like behaviors, and astrocyte activity in male Wistar rats.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2025Article
- Optimization of Transcardiac Perfusion for More Accurately Evaluating Biodistribution of Large Molecules.International journal of molecular sciences · 2024Article
- Monoacylglycerol Lipase Protects the Presynaptic Cannabinoid 1 Receptor from Desensitization by Endocannabinoids after Persistent Inflammation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Ventrolateral Periaqueductal Gray Astrocytes Regulate Nociceptive Sensation and Emotional Motivation in Diabetic Neuropathic Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Sex differences in morphine sensitivity are associated with differential glial expression in the brainstem of rats with neuropathic pain.Journal of neuroscience research · 2022Article
- Opioid-induced microglia reactivity modulates opioid reward, analgesia, and behavior.Neuroscience and biobehavioral reviews · 2022Review
- Long-Term Exposure to Morphine Induces Cross-Tolerance to Acute Antinociceptive Effect of Remifentanil on Somatic and Visceral Stimuli in Rats.Journal of pain research · 2022Article
- Cellular and circuit diversity determines the impact of endogenous opioids in the descending pain modulatory pathway.Frontiers in systems neuroscience · 2022Review
- Dihydroartemisinin alleviates morphine-induced neuroinflammation in BV-2 cells.Bioengineered · 2021Article
- Review
- Aberrant Feeding and Growth in Neonates With Prenatal Opioid Exposure: Evidence of Neuromodulation and Behavioral Changes.Frontiers in pediatrics · 2021Review
- On the Role of Peripheral Sensory and Gut Mu Opioid Receptors: Peripheral Analgesia and Tolerance.Molecules (Basel, Switzerland) · 2020Review
- Potentiation of morphine-induced antinociception by harmaline: involvement of μ-opioid and ventral tegmental area NMDA receptors.Psychopharmacology · 2020Article
- μ Opioid Receptor-Triggered Notch-1 Activation Contributes to Morphine Tolerance: Role of Neuron-Glia Communication.Molecular neurobiology · 2020Article
- Inflammatory mediators of opioid tolerance: Implications for dependency and addiction.Peptides · 2019Review
- Emerging roles of microRNAs in morphine tolerance.Journal of pain research · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledMorphine is among the most prevalent analgesics prescribed for chronic pain. However, prolonged morphine treatment results in the development of analgesic tolerance. An abundance of evidence has accumulated indicating that central nervous system glial cell activity facilitates pain transmission and opposes morphine analgesia. While the midbrain ventrolateral periaqueductal gray (vlPAG) is an important neural substrate mediating pain modulation and the development of morphine tolerance, no studies have directly assessed the role of PAG glia. Here we test the hypothesis that morphine-induced increases in vlPAG glial cell activity contribute to the development of morphine tolerance. As morphine is primarily consumed for the alleviation of severe pain, the influence of persistent inflammatory pain was also assessed. Administration of morphine, in the absence of persistent inflammatory pain, resulted in the rapid development of morphine tolerance and was accompanied by a significant increase in vlPAG glial activation. In contrast, persistent inflammatory hyperalgesia, induced by intraplantar administration of complete Freund's adjuvant (CFA), significantly attenuated the development of morphine tolerance. No significant differences were noted in vlPAG glial cell activation for CFA-treated animals versus controls. These results indicate that vlPAG glia are modulated by a persistent pain state, and implicate vlPAG glial cells as possible regulators of morphine tolerance. PERSPECTIVE: The development of morphine tolerance represents a significant impediment to its use in the management of chronic pain. We report that morphine tolerance is accompanied by increased glial cell activation within the vlPAG, and that the presence of a persistent pain state prevented vlPAG glial activation and attenuated morphine tolerance.
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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.