ArticlePharmacological research2019
The antidiabetic drug metformin prevents and reverses neuropathic pain and spinal cord microglial activation in male but not female mice.
Article in Pharmacological research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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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.
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Who cites it
79 citing papers in PubMed, 129 citations in OpenAlex.
- Safety and efficacy of metformin for the treatment of pain: protocol for a systematic review.BMJ open · 2026Article
- Repurposed Systemic Pharmacologic Agents in Chronic Pain: Emerging Mechanistic and Clinical Insights.Journal of clinical medicine · 2026Review
- The role of gut microbiota in neuropathic pain: insights into immune mechanisms.The journal of headache and pain · 2025Review
- Neuroprotective Roles of Metformin in a Streptozotocin-Induced Dementia Model in Rats.Neurotoxicity research · 2025Article
- Early Life Injury Alters Spinal Astrocyte Development.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Beyond inflammation: a comprehensive microglial regulation model in chronic pain.Molecular biology reports · 2025Review
- Preclinical Assessment of a Metformin-Melatonin Combination: Antinociceptive Synergism.Pharmaceutics · 2025Article
- Mechanism-based nonopioid analgesic targets.The Journal of clinical investigation · 2025Review
- Monocyte eukaryotic initiation factor 2 signaling differentiates 17-hydroxy-docosahexaenoic acid levels and pain.iScience · 2025Article
- Intravenous Streptozotocin Induces Variants in Painful Diabetic Peripheral Neuropathy in Female Mice.Journal of pain research · 2025Article
- Metformin and fibromyalgia pathophysiology: current insights and promising future therapeutic strategies.Molecular biology reports · 2024Review
- Article
- The influence of sex on neuroimmune communication, pain, and physiology.Biology of sex differences · 2024Review
- Article
- Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024Review
- A Mechanism of Action of Metformin in the Brain: Prevention of Methylglyoxal-Induced Glutamatergic Impairment in Acute Hippocampal Slices.Molecular neurobiology · 2024Article
- Targeting Prefrontal Cortex Dysfunction in Pain.The Journal of pharmacology and experimental therapeutics · 2024Review
- Review
- Role of microglia in diabetic neuropathic pain.Frontiers in cell and developmental biology · 2024Review
- Stathmin-2 loss leads to neurofilament-dependent axonal collapse driving motor and sensory denervation.Nature neuroscience · 2024Article
19 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Metformin is a widely prescribed drug used in the treatment of type II diabetes. While the drug has many mechanisms of action, most of these converge on AMP activated protein kinase (AMPK), which metformin activates. AMPK is a multifunctional kinase that is a negative regulator of mechanistic target of rapamycin (mTOR) and mitogen activated protein kinase (MAPK) signaling. Activation of AMPK decreases the excitability of dorsal root ganglion neurons and AMPK activators are effective in reducing chronic pain in inflammatory, post-surgical and neuropathic rodent models. We have previously shown that metformin leads to an enduring resolution of neuropathic pain in the spared nerve injury (SNI) model in male mice and rats. The precise mechanism underlying this long-lasting effect is not known. We conducted experiments to investigate the effects of metformin on SNI-induced microglial activation, a process implicated in the maintenance of neuropathic pain that has recently been shown to be sexually dimorphic. We find that metformin is effective at inhibiting development of neuropathic pain when treatment is given around the time of injury and that metformin is likewise effective at reversing neuropathic mechanical hypersensitivity when treatment is initiation weeks after injury. This effect is linked to decreased Iba-1 staining in the dorsal horn, a marker of microglial activation. Importantly, these positive behavioral and microglia effects of metformin were only observed in male mice. We conclude that the neuropathic pain modifying effects of metformin are sex-specific supporting a differential role for microglial activation in male and female mice.
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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.