ArticleNeuroscience bulletin2014
Toll-like receptor 4-mediated nuclear factor-κB activation in spinal cord contributes to chronic morphine-induced analgesic tolerance and hyperalgesia in rats.
Article in Neuroscience bulletin, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 68 citations in OpenAlex.
- The actions of morphine on microglia and the underlying effects on associated adverse effects.Psychopharmacology · 2026Review
- Network pharmacology approach to unveiling the mechanism of berberine in the amelioration of morphine tolerance.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Article
- The therapeutic potential of phytochemicals in morphine tolerance: targeting microglia-mediated neuroinflammation.Frontiers in pharmacology · 2025Review
- Morphine-Driven m6A Epitranscriptomic Neuroadaptations in Primary Cortical Cultures.Molecular neurobiology · 2024Article
- Mu-Opioid Receptor (MOR) Dependence of Pain in Chemotherapy-Induced Peripheral Neuropathy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Elucidating the molecular symphony: unweaving the transcriptional & epigenetic pathways underlying neuroplasticity in opioid dependence and withdrawal.Psychopharmacology · 2024Review
- YTHDF1 in periaqueductal gray inhibitory neurons contributes to morphine withdrawal responses in mice.BMC medicine · 2024Article
- Review
- The YTHDF1-TRAF6 pathway regulates the neuroinflammatory response and contributes to morphine tolerance and hyperalgesia in the periaqueductal gray.Journal of neuroinflammation · 2022Article
- Elevated serum TLR4 level as a potential marker for postsurgical chronic pain in pediatric patients with different approaches to analgesia.Frontiers in medicine · 2022Article
- Morphine-3-Glucuronide, Physiology and Behavior.Frontiers in molecular neuroscience · 2022Review
- Dihydroartemisinin alleviates morphine-induced neuroinflammation in BV-2 cells.Bioengineered · 2021Article
- The different mechanisms of peripheral and central TLR4 on chronic postsurgical pain in rats.Journal of anatomy · 2021Article
- Pellino1 Contributes to Morphine Tolerance by Microglia Activation via MAPK Signaling in the Spinal Cord of Mice.Cellular and molecular neurobiology · 2020Article
- Chronic morphine-mediated upregulation of high mobility group box 1 in the spinal cord contributes to analgesic tolerance and hyperalgesia in rats.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Article
- Oleanolic acid administration alleviates neuropathic pain after a peripheral nerve injury by regulating microglia polarization-mediated neuroinflammation.RSC advances · 2020Article
- Opioid Receptors in Immune and Glial Cells-Implications for Pain Control.Frontiers in immunology · 2020Review
- Opioid-Induced Hyperalgesia Is Associated with Dysregulation of Circadian Rhythm and Adaptive Immune Pathways in the Mouse Trigeminal Ganglia and Nucleus Accumbens.Molecular neurobiology · 2019Article
- Circular RNA expression profile in the spinal cord of morphine tolerated rats and screen of putative key circRNAs.Molecular brain · 2019Article
- Role of Nociceptor Toll-like Receptor 4 (TLR4) in Opioid-Induced Hyperalgesia and Hyperalgesic Priming.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nuclear factor kappa B (NF-κB) in the spinal cord is involved in pro-inflammatory cytokine-mediated pain facilitation. However, the role of NF-κB activation in chronic morphine-induced analgesic tolerance and the underlying mechanisms remain unclear. In the present study, we found that the level of phosphorylated NF-κB p65 (p-p65) was increased in the dorsal horn of the lumbar 4-6 segments after intrathecal administration of morphine for 7 consecutive days, and the p-p65 was co-localized with neurons and astrocytes. The expression of TNF-α and IL-1β was also increased in the same area. In addition, pretreatment with pyrrolidinedithiocarbamate (PDTC) or SN50, inhibitors of NF-κB, prevented the development of morphine analgesic tolerance and alleviated morphine withdrawal-induced allodynia and hyperalgesia. The increase in TNF-α and IL-1β expression induced by chronic morphine exposure was also partially blocked by PDTC pretreatment. In another experiment, rats receiving PDTC or SN50 beginning on day 7 of morphine injection showed partial recovery of the anti-nociceptive effects of morphine and attenuation of the withdrawal-induced abnormal pain. Meanwhile, intrathecal pretreatment with lipopolysaccharide from Rhodobacter sphaeroides, an antagonist of toll-like receptor 4 (TLR4), blocked the activation of NF-κB, and prevented the development of morphine tolerance and withdrawal-induced abnormal pain. These data indicated that TLR4-mediated NF-κB activation in the spinal cord is involved in the development and maintenance of morphine analgesic tolerance and withdrawal-induced pain hypersensitivity.
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