ArticleBrain, behavior, and immunity2018
Protraction of neuropathic pain by morphine is mediated by spinal damage associated molecular patterns (DAMPs) in male rats.
Article in Brain, behavior, and immunity, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 2 of them syntheses that pooled it.
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Who cites it
51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 77 citations in OpenAlex.
- Pyroptosis in Peripheral Neuropathy: From Molecular Mechanisms to Therapeutic Targeting.CNS neuroscience & therapeutics · 2026Pooled it
- P2X7 receptor as a key player in pathological pain: insights into Neuropathic, inflammatory, and cancer pain.Frontiers in pharmacology · 2025Pooled it
- 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
- Spinal NLRP3 blockade reverses morphine-prolonged neuropathic pain and proinflammatory immune actions in prenatal alcohol-exposed male mice.Neuropharmacology · 2026Article
- The actions of morphine on microglia and the underlying effects on associated adverse effects.Psychopharmacology · 2026Review
- Association Between Heroin Use and Depression: NHANES 2005-2018.Addiction biology · 2026Article
- 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
- Marine-derived bioactive compounds for neuropathic pain: pharmacology and therapeutic potential.Naunyn-Schmiedeberg's archives of 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
- Inhibiting spinal cord-specific hsp90 isoforms reveals a novel strategy to improve the therapeutic index of opioid treatment.Scientific reports · 2024Article
- NLRs and inflammasome signaling in opioid-induced hyperalgesia and tolerance.Inflammopharmacology · 2024Review
- Interleukin-1beta and inflammasome expression in spinal cord following chronic constriction injury in male and female rats.Brain, behavior, and immunity · 2024Article
- Involvement of microglial P2X7 receptor in pain modulation.CNS neuroscience & therapeutics · 2024Review
- Spinal HMGB1 participates in the early stages of paclitaxel-induced neuropathic pain via microglial TLR4 and RAGE activation.Frontiers in immunology · 2024Article
- Prenatal alcohol exposure promotes NLRP3 inflammasome-dependent immune actions following morphine treatment and paradoxically prolongs nerve injury-induced pathological pain in female mice.Alcohol, clinical & experimental research · 2023Article
- The FDA-approved compound, pramipexole and the clinical-stage investigational drug, dexpramipexole, reverse chronic allodynia from sciatic nerve damage in mice, and alter IL-1β and IL-10 expression from immune cell culture.Neuroscience letters · 2023Article
- Microglia NLRP3 Inflammasome and Neuroimmune Signaling in Substance Use Disorders.Biomolecules · 2023Review
- The Downregulation of Opioid Receptors and Neuropathic Pain.International journal of molecular sciences · 2023Review
- Neuropathic pain; what we know and what we should do about it.Frontiers in pain research (Lausanne, Switzerland) · 2023Review
- The Crosstalk between the Blood-Brain Barrier Dysfunction and Neuroinflammation after General Anaesthesia.Current issues in molecular biology · 2022Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
We have recently reported that a short course of morphine, starting 10days after sciatic chronic constriction injury (CCI), prolonged the duration of mechanical allodynia for months after morphine ceased. Maintenance of this morphine-induced persistent sensitization was dependent on spinal NOD-like receptor protein 3 (NLRP3) inflammasomes-protein complexes that proteolytically activate interleukin-1β (IL-1β) via caspase-1. However, it is still unclear how NLRP3 inflammasome signaling is maintained long after morphine is cleared. Here, we demonstrate that spinal levels of the damage associated molecular patterns (DAMPs) high mobility group box 1 (HMGB1) and biglycan are elevated during morphine-induced persistent sensitization in male rats; that is, 5weeks after cessation of morphine dosing. We also show that HMGB1 and biglycan levels are at least partly dependent on the initial activation of caspase-1, as well as Toll like receptor 4 (TLR4) and the purinergic receptor P2X7R-receptors responsible for priming and activation of NLRP3 inflammasomes. Finally, pharmacological attenuation of the DAMPs HMGB1, biglycan, heat shock protein 90 and fibronectin persistently reversed morphine-prolonged allodynia. We conclude that after peripheral nerve injury, morphine treatment results in persistent DAMP release via TLR4, P2X7R and caspase-1, which are involved in formation/activation of NLRP3 inflammasomes. These DAMPs are responsible for maintaining persistent allodynia, which may be due to engagement of a positive feedback loop, in which NLRP3 inflammasomes are persistently activated by DAMPs signaling at TLR4 and P2X7R.
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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.