ArticleJournal of inflammation research2020
Spinal TLR4/P2X7 Receptor-Dependent NLRP3 Inflammasome Activation Contributes to the Development of Tolerance to Morphine-Induced Antinociception.
Article in Journal of inflammation research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 25 citations in OpenAlex.
- The actions of morphine on microglia and the underlying effects on associated adverse effects.Psychopharmacology · 2026Review
- The analgesic effect of electroacupuncture in alleviating paclitaxel-induced peripheral neuropathic pain and its possible mechanism relates to TLR4/P2X7-NLRP3 signaling pathway.Purinergic signalling · 2026Article
- Evaluation of AT121 versus morphine on cortical neurons electrophysiology and dopamine concentrations in hippocampal cells.PloS one · 2026Article
- Transcutaneous Electrical Acupoint Stimulation for Opioid Tolerance in Hepatocellular Carcinoma and Proteomics Analysis: A Randomized Controlled Trial Protocol.Journal of pain research · 2026Article
- Zonisamide attenuates morphine tolerance in association with reduced spinal TLR4/p38 MAPK signaling.Frontiers in pharmacology · 2026Article
- NLRP3 inflammasome: a key driver of neuroinflammation and a novel therapeutic target for neuropathic pain.Anesthesia and pain medicine · 2025Review
- Time-restricted feeding modulates neuron-glial interactions and circadian rhythm in the spinal cord of male Wistar rats fed a high-fat diet.Spinal cord · 2025Article
- Decoding NLRP3 Inflammasome Activation in Alzheimer's Disease: A Focus on Receptor Dynamics.Molecular neurobiology · 2025Review
- Microglial pyroptosis as a therapeutic target after traumatic spinal cord injury: current progress and future directions.Frontiers in immunology · 2025Review
- The therapeutic potential of phytochemicals in morphine tolerance: targeting microglia-mediated neuroinflammation.Frontiers in pharmacology · 2025Review
- The effect of cannabinoid type 2 receptor agonist on morphine tolerance.IBRO neuroscience reports · 2024Review
- Microglia in morphine tolerance: cellular and molecular mechanisms and therapeutic potential.Frontiers in pharmacology · 2024Review
- Effect of NLRP3 inflammasome induced astrocyte phenotype alteration in morphine tolerance.Frontiers in pharmacology · 2024Article
- Role of the P2 × 7 receptor in neurodegenerative diseases and its pharmacological properties.Cell & bioscience · 2023Review
- Neuromodulation in Parkinson's disease targeting opioid and cannabinoid receptors, understanding the role of NLRP3 pathway: a novel therapeutic approach.Inflammopharmacology · 2023Review
- Emerging roles of the P2X7 receptor in cancer pain.Purinergic signalling · 2023Review
- Microglia NLRP3 Inflammasome and Neuroimmune Signaling in Substance Use Disorders.Biomolecules · 2023Review
- Angiotensin II receptor type 1 blocker candesartan improves morphine tolerance by reducing morphine‑induced inflammatory response and cellular activation of BV2 cells via the PPARγ/AMPK signaling pathway.Molecular medicine reports · 2022Article
- Cannabidivarin alleviates neuroinflammation by targeting TLR4 co-receptor MD2 and improves morphine-mediated analgesia.Frontiers in immunology · 2022Article
- Endogenous opioid systems alterations in pain and opioid use disorder.Frontiers in systems neuroscience · 2022Review
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 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLong-term use of morphine induces antinociceptive tolerance and limits its clinical efficacy. Neuroinflammation in the spinal cord is thought to play a pivotal role in the development of morphine tolerance. Toll-like receptor 4 (TLR4) and P2X7 receptor (P2X7R) are key modulators of neuroinflammation. Recent studies show that the Nod-like receptor protein 3 (NLRP3) inflammasome play a crucial role in microglia-mediated neuroinflammation. Thus far, the mechanism underlying NLRP3 inflammasome activation during morphine-induced tolerance is not yet fully understood. Therefore, we sought to investigate the mechanisms of NLRP3 inflammasome activation and its role in the development of morphine-induced tolerance.
methodsRepeated morphine treatment through intrathecal injection (15 μg once daily for 7 days) was given to establish antinociceptive tolerance in mice. Tail-flick latency was used to evaluate morphine-induced antinociception. NLRP3 knockout mice were used to assess the role of NLRP3 inflammasome in morphine tolerance. TLR4 knockout mice and A438079, a P2X7R antagonist, were used to assess the role of TLR4 and P2X7R in chronic morphine-induced NLRP3 inflammasome activation. Western blot and immunofluorescence were used for quantitative comparison.
resultsRepeated morphine treatment increased the expression of NLRP3. Knockout of NLRP3 attenuated morphine-induced tolerance and suppressed morphine-induced activation of microglia. Knockout of TLR4 alleviated morphine tolerance and chronic morphine-induced upregulation of spinal NLRP3. Inhibition of spinal P2X7R with A438079 not only prevented the development of morphine-induced tolerance but also inhibited repeated morphine treatment-induced upregulation of spinal NLRP3. Furthermore, spinal NLRP3, TLR4 and P2X7R were collectively colocalized with the microglia marker Iba1.
conclusionThis study demonstrates that the NLRP3 inflammasome in microglia plays a crucial role in morphine tolerance and that both TLR4- and P2X7R-dependent pathways are required for NLRP3 inflammasome activation over the course of the development of morphine-induced tolerance. Our results provide a new perspective for the targeted treatment of morphine-induced tolerance.
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.