ArticleJournal of cellular and molecular medicine2019
Metformin relieves neuropathic pain after spinal nerve ligation via autophagy flux stimulation.
Article in Journal of cellular and molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 42 citations in OpenAlex.
- Metformin's therapeutic potential in spinal cord injury: a systematic review and meta-analysis on locomotor recovery, neuropathic pain alleviation, and modulation of secondary injury mechanisms.Acta neurochirurgica · 2025Pooled it
- Pooled it
- Novel Insights into the Management of Painful Trigeminal Neuropathy: Targeting Peripheral and Central Pathomechanisms.Journal of pain research · 2026Review
- Novel mechanistic insights of the potential role of gasotransmitters and autophagy in the protective effect of metformin against hepatic ischemia/reperfusion injury in rats.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Metformin and fibromyalgia pathophysiology: current insights and promising future therapeutic strategies.Molecular biology reports · 2024Review
- Article
- Store-operated calcium entry mediates hyperalgesic responses during neuropathy.FEBS open bio · 2023Article
- Article
- Sex Differences in Neuropathy: The Paradigmatic Case of MetFormin.International journal of molecular sciences · 2022Article
- Inflammatory-associated apoptotic markers: are they the culprit to rheumatoid arthritis pain?Molecular biology reports · 2022Review
- Curcumin and metformin synergistically modulate peripheral and central immune mechanisms of pain.Scientific reports · 2022Article
- Caloric Restriction Alleviates CFA-Induced Inflammatory PainFrontiers in neuroscience · 2022Article
- Review: Myelin clearance is critical for regeneration after peripheral nerve injury.Frontiers in neurology · 2022Review
- Article
- P2X7R-mediated autophagic impairment contributes to central sensitization in a chronic migraine model with recurrent nitroglycerin stimulation in mice.Journal of neuroinflammation · 2021Article
- Role of the Ubiquitin System in Chronic Pain.Frontiers in molecular neuroscience · 2021Review
- Protectin DX Attenuates Lumbar Radicular Pain of Non-compressive Disc Herniation by Autophagy Flux StimulationFrontiers in physiology · 2021Article
- Metformin limits osteoarthritis development and progression through activation of AMPK signalling.Annals of the rheumatic diseases · 2020Article
- p66shc siRNA-Encapsulated PLGA Nanoparticles Ameliorate Neuropathic Pain Following Spinal Nerve Ligation.Polymers · 2020Article
- Exploration of metformin as novel therapy for osteoarthritis: preventing cartilage degeneration and reducing pain behavior.Arthritis research & therapy · 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
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuropathic pain is a well-known type of chronic pain caused by damage to the nervous system. Autophagy is involved in the development and/or progression of many diseases, including neuropathic pain. Emerging evidence suggests that metformin relieves neuropathic pain in several neuropathic pain models; however, metformin's cellular and molecular mechanism for pain relief remains unknown. In this study, we investigated the therapeutic effects of metformin on pain relief after spinal nerve ligation (SNL) and its underlying mechanism of autophagy regulation. Behavioural analysis, histological assessment, expression of c-Fos and molecular biological changes, as well as ultrastructural features, were investigated. Our findings showed that the number of autophagosomes and expression of autophagy markers, such as LC3 and beclin1, were increased, while the autophagy substrate protein p62, as well as the ubiquitinated proteins, were accumulated in the ipsilateral spinal cord. However, metformin enhanced the expression of autophagy markers, while it abrogated the abundance of p62 and ubiquitinated proteins. Blockage of autophagy flux by chloroquine partially abolished the apoptosis inhibition and analgesic effects of metformin on SNL. Taken together, these results illustrated that metformin relieved neuropathic pain through autophagy flux stimulation and provided a new direction for metformin drug development to treat neuropathic pain.
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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.