ArticleFrontiers in cell and developmental biology2020
Rescue of HSP70 in Spinal Neurons Alleviates Opioids-Induced Hyperalgesia via the Suppression of Endoplasmic Reticulum Stress in Rodents.
Article in Frontiers in cell and developmental biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Endoplasmic Reticulum Stress in Spinal Cord Injury: Pathological Roles, Molecular Targets, and Emerging Treatments: A Systematic Review.Molecular neurobiology · 2026Pooled it
- Modulation of Endoplasmic Reticulum Stress via CEBPB: A Potential Molecular Link to Therapeutic Action in Substance Use Disorders.CNS neuroscience & therapeutics · 2026Article
- Mitochondrial Dysfunction and Endoplasmic Reticulum Stress in Chronic Pain.Brain sciences · 2026Review
- Heat shock protein 70 in Cynops orientalis: bidirectional thermal regulation and metabolic optimization in amphibian climatic adaptation.BMC genomics · 2026Article
- Unidirectional Crosstalk Between NTRK1 and IGF2 Drives ER Stress in Chronic Pain.Biomedicines · 2025Article
- Cancer pain: molecular mechanisms and management.Molecular biomedicine · 2025Review
- Protein Misfolding and Aggregation as a Mechanistic Link Between Chronic Pain and Neurodegenerative Diseases.Current issues in molecular biology · 2025Review
- Targeted Regulation of HSP70 by the ARP2/3 Complex in Mammary Epithelial Cells and Its Impact on Host Cell Apoptosis.Biomolecules · 2025Article
- Astrocytic pyruvate dehydrogenase kinase-lactic acid axis involvement in glia-neuron crosstalk contributes to morphine-induced hyperalgesia in mice.Fundamental research · 2024Article
- Unraveling the Connection: Pain and Endoplasmic Reticulum Stress.International journal of molecular sciences · 2024Review
- Endoplasmic reticular stress as an emerging therapeutic target for chronic pain: a narrative review.British journal of anaesthesia · 2024Review
- SHED-derived exosomes attenuate trigeminal neuralgia after CCI of the infraorbital nerve in mice via the miR-24-3p/IL-1R1/p-p38 MAPK pathway.Journal of nanobiotechnology · 2023Article
- Sex-dependent differences in the genomic profile of lingual sensory neurons in naïve and tongue-tumor bearing mice.Scientific reports · 2023Article
- Sex-dependent Differences in the Genomic Profile of Lingual Sensory Neurons in Naïve and Tongue-Tumor Bearing Mice.bioRxiv : the preprint server for biology · 2023Article
- Sinomenine alleviates diabetic peripheral neuropathic pain through inhibition of the inositol-requiring enzyme 1 alpha-X-box binding protein 1 pathway by downregulating prostaglandin-endoperoxide synthase 2.Journal of diabetes investigation · 2023Article
- Docetaxel-induced cognitive impairment in rats can be ameliorated by edaravone dexborneol: Evidence from the indicators of biological behavior and anisotropic fraction.Frontiers in neuroscience · 2023Article
- Pharmacological Interventions for Opioid-Induced Hyperalgesia: A Scoping Review of Preclinical Trials.Journal of clinical medicine · 2022Article
- The Proteostasis Network: A Global Therapeutic Target for Neuroprotection after Spinal Cord Injury.Cells · 2022Review
- AMPK-autophagy-mediated inhibition of microRNA-30a-5p alleviates morphine tolerance via SOCS3-dependent neuroinflammation suppression.Journal of neuroinflammation · 2022Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A major unresolved issue in treating pain is the paradoxical hyperalgesia produced by the gold-standard analgesic morphine and other opioids. Endoplasmic reticulum (ER) stress has been shown to contribute to neuropathic or inflammatory pain, but its roles in opioids-induced hyperalgesia (OIH) are elusive. Here, we provide the first direct evidence that ER stress is a significant driver of OIH. GRP78, the ER stress marker, is markedly upregulated in neurons in the spinal cord after chronic morphine treatment. At the same time, morphine induces the activation of three arms of unfolded protein response (UPR): inositol-requiring enzyme 1α/X-box binding protein 1 (IRE1α/XBP1), protein kinase RNA-like ER kinase/eukaryotic initiation factor 2 subunit alpha (PERK/eIF2α), and activating transcription factor 6 (ATF6). Notably, we found that inhibition on either IRE1α/XBP1 or ATF6, but not on PERK/eIF2α could attenuate the development of OIH. Consequently, ER stress induced by morphine enhances PKA-mediated phosphorylation of NMDA receptor subunit 1(NR1) and leads to OIH. We further showed that heat shock protein 70 (HSP70), a molecular chaperone involved in protein folding in ER, is heavily released from spinal neurons after morphine treatment upon the control of K
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