ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2020
Chronic morphine-mediated upregulation of high mobility group box 1 in the spinal cord contributes to analgesic tolerance and hyperalgesia in rats.
Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 42 citations in OpenAlex.
- Effects of MC-100093, GLT-1 enhancer, in mesolimbic brain regions of C57BL/6 mouse exposed to hydrocodone high-dose challenge using comprehensive laboratory monitoring system.IBRO neuroscience reports · 2026Article
- Downregulation of Neuralized1 in the Hippocampal CA1 Through Reducing CPEB3 Ubiquitination Mediates Synaptic Plasticity Impairment and Cognitive Deficits in Neuropathic Pain.Neuroscience bulletin · 2025Article
- Prenatal alcohol exposure promotes nerve injury-induced pathological pain following morphine treatment via NLRP3-mediated peripheral and central proinflammatory immune actions.Brain, behavior, and immunity · 2025Article
- The Receptor for Advanced Glycation End-products in the Mouse Anterior Cingulate Cortex is Involved in Neuron‒Astrocyte Coupling in Chronic Inflammatory Pain and Anxiety Comorbidity.Molecular neurobiology · 2025Article
- The therapeutic potential of phytochemicals in morphine tolerance: targeting microglia-mediated neuroinflammation.Frontiers in pharmacology · 2025Review
- 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
- The effect of cannabinoid type 2 receptor agonist on morphine tolerance.IBRO neuroscience reports · 2024Review
- Upregulation of lysine-specific demethylase 6B aggravates inflammatory pain through H3K27me3 demethylation-dependent production of TNF-α in the dorsal root ganglia and spinal dorsal horn in rats.CNS neuroscience & therapeutics · 2023Article
- Suppressing high mobility group box-1 release alleviates morphine tolerance via the adenosine 5'-monophosphate-activated protein kinase/heme oxygenase-1 pathway.Neural regeneration research · 2023Article
- The role of neuroinflammation in the transition of acute to chronic pain and the opioid-induced hyperalgesia and tolerance.Frontiers in pharmacology · 2023Review
- Fecal Microbiota Transplantation Alleviated Paclitaxel-Induced Peripheral Neuropathy by Interfering with Astrocytes and TLR4/p38MAPK Pathway in Rats.Journal of pain research · 2023Article
- The YTHDF1-TRAF6 pathway regulates the neuroinflammatory response and contributes to morphine tolerance and hyperalgesia in the periaqueductal gray.Journal of neuroinflammation · 2022Article
- Activation of Double-Stranded RNA-Activated Protein Kinase in the Dorsal Root Ganglia and Spinal Dorsal Horn Regulates Neuropathic Pain Following Peripheral Nerve Injury in Rats.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- AMPK-autophagy-mediated inhibition of microRNA-30a-5p alleviates morphine tolerance via SOCS3-dependent neuroinflammation suppression.Journal of neuroinflammation · 2022Article
- Review
- Article
- Suppression of TLR4-MyD88 signaling pathway attenuated chronic mechanical pain in a rat model of endometriosis.Journal of neuroinflammation · 2021Article
- Liquorice for pain?Therapeutic advances in psychopharmacology · 2021Review
- Toll-Like Receptor 4 (TLR4)/Opioid Receptor Pathway Crosstalk and Impact on Opioid Analgesia, Immune Function, and Gastrointestinal Motility.Frontiers in immunology · 2020Review
- Spinal TLR4/P2X7 Receptor-Dependent NLRP3 Inflammasome Activation Contributes to the Development of Tolerance to Morphine-Induced Antinociception.Journal of inflammation research · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Analgesic tolerance and hyperalgesia hinder the long-term utility of opioids. We examined whether spinal high mobility group box 1 (HMGB1) is involved in morphine tolerance and its underlying mechanisms by using a model of repeated intrathecal (i.t.) injections of morphine. The results showed that chronic i.t. morphine exposure led to increased expression of HMGB1, Toll-like receptor 4 (TLR4), and receptor for advanced glycation end products (RAGE) and their mRNAs in the dorsal horn. Morphine challenge also promoted HMGB1 expression and release in cultured spinal neurons, but these effects were inhibited by TAK-242, naloxone (antagonists of TLR4), and TLR4 siRNA. Intrathecal coadministration of morphine with TAK-242 or PDTC (inhibitor of NF-κB activation) also reduced HMGB1 expression in the spinal cord. Repeated i.t. coinjections of morphine with glycyrrhizin (GL, an HMGB1 inhibitor) or HMGB1 siRNA prevented reduction of the maximal possible analgesic effect (MPAE) of morphine and alleviated morphine withdrawal-induced hyperalgesia. The established morphine tolerance and hyperalgesia were partially reversed when i.t. injections of GL or HMGB1 antibody started at day 7 of morphine injection. Repeated i.t. injections of morphine with HMGB1 siRNA inhibited the activation of NF-κB, but not that of JNK and p38. A single i.t. injection of HMGB1 in naïve rats caused pain-related hypersensitivity and reduction in MPAE. Moreover, phosphorylated NF-κB p65, TNF-α, and IL-1β levels in the dorsal horn were upregulated following this treatment, but this upregulation was prevented by coinjection with TAK-242. Together, these results suggest that morphine-mediated upregulation of spinal HMGB1 contributes to analgesic tolerance and hyperalgesia via activation of TLR4/NF-κB signaling, and the HMGB1 inhibitor might be a promising adjuvant to morphine in the treatment of intractable pain in the clinic.
Indexed as
Identifiers
What OpenQuestion holds
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.