ArticleFrontiers in molecular neuroscience2018
Endoplasmic Reticulum Stress in Spinal Cord Contributes to the Development of Morphine Tolerance.
Article in Frontiers in molecular neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Endoplasmic Reticulum Stress in Spinal Cord Injury: Pathological Roles, Molecular Targets, and Emerging Treatments: A Systematic Review.Molecular neurobiology · 2026Pooled it
- Role of Muscarinic Receptor Signaling Processes in Specific Aspects of Morphine-Induced Respiratory Depression in Rats.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Exploring the Role of RhoA/ROCK Signaling in Pain: A Narrative Review.Aging and disease · 2025Review
- C3/C3aR Bridges Spinal Astrocyte-Microglia Crosstalk and Accelerates Neuroinflammation in Morphine-Tolerant Rats.CNS neuroscience & therapeutics · 2025Article
- Toll-like Receptor 2-Melatonin Feedback Loop Regulates the Activation of Spinal NLRP3 Inflammasome in Morphine-Tolerant Rats.Neurochemical research · 2023Article
- Targeting the nitric oxide/cGMP signaling pathway to treat chronic pain.Neural regeneration research · 2023Review
- NADPH-Oxidase 2 Promotes Autophagy in Spinal Neurons During the Development of Morphine Tolerance.Neurochemical research · 2021Article
- Neuropathic Pain in Multiple Sclerosis and Its Animal Models: Focus on Mechanisms, Knowledge Gaps and Future Directions.Frontiers in neurology · 2021Review
- Nrf2 Activation Attenuates Chronic Constriction Injury-Induced Neuropathic Pain via Induction of PGC-1Oxidative medicine and cellular longevity · 2021Article
- Anakinra, an interleukin-1 receptor antagonist, increases the morphine analgesic effect and decreases morphine tolerance development by modulating oxidative stress and endoplasmic reticulum stress in ratsTurkish journal of medical sciences · 2020Article
- Spinal heat shock protein 27 participates in PDGFRβ-mediated morphine tolerance through PI3K/Akt and p38 MAPK signalling pathways.British journal of pharmacology · 2020Article
- Titanium dioxide nanoparticles induce endoplasmic reticulum stress-mediated apoptotic cell death in liver cancer cells.The Journal of international medical research · 2020Article
- Rescue of HSP70 in Spinal Neurons Alleviates Opioids-Induced Hyperalgesia via the Suppression of Endoplasmic Reticulum Stress in Rodents.Frontiers in cell and developmental biology · 2020Article
- The Interaction Between Spinal PDGFRβ and μ Opioid Receptor in the Activation of Microglia in Morphine-Tolerant Rats.Journal of pain research · 2020Article
- Proteomic profiling of proteins in the dorsal horn of the spinal cord in dairy cows with chronic lameness.PloS one · 2020Article
- Sigma-1 receptor modulates neuroinflammation associated with mechanical hypersensitivity and opioid tolerance in a mouse model of osteoarthritis pain.British journal of pharmacology · 2019Article
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Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Morphine tolerance remains an intractable problem, which hinders its prolonged use in clinical practice. Endoplasmic reticulum (ER) stress has been proved to play a fundamental role in the pathogenesis of Alzheimer's disease, diabetes, atherosclerosis, cancer, etc. In this study, we provide the first direct evidence that ER stress may be a significant driver of morphine tolerance. Binding immunoglobulin protein (BiP), the ER stress marker, was significantly upregulated in neurons in spinal dorsal horn in rats being treated with morphine for 7 days. Additionally, chronic morphine treatment resulted in the activation of three arms of unfolded protein response (UPR): inositol-requiring enzyme 1/X-box binding protein 1 (IRE1/XBP1), protein kinase RNA-like ER kinase/eukaryotic initiation factor 2 subunit alpha (PERK/eIF2α), and activating transcription factor 6 (ATF6). More importantly, inhibiting either one of the three cascades could attenuate the development of morphine tolerance. Taken together, our results suggest that ER stress in spinal cord might contribute to the development of morphine tolerance. These findings implicate a potential clinical strategy for preventing morphine tolerance and may contribute to expanding the morphine usage in clinic.
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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.