ArticleThe Journal of clinical investigation2017
Selective antagonism of muscarinic receptors is neuroprotective in peripheral neuropathy.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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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.
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Who cites it
55 citing papers in PubMed, 89 citations in OpenAlex.
- A muscarinic receptor antagonist reverses multiple indices of diabetic peripheral neuropathy: preclinical and clinical studies using oxybutynin.Acta neuropathologica · 2024Trial
- Discovery of VU6077564: A Selective MACS chemical neuroscience · 2026Article
- Redox and bioenergetic modulation by plumbagin attenuated neuropathic allodynia in mice with diet-induced diabetes.Nutrition & diabetes · 2026Article
- Mechanisms, translational opportunities for diabetic polyneuropathy.Frontiers in endocrinology · 2026Review
- Exploring the Effects of Palm Tocotrienol-Rich Fraction in Diabetic Peripheral Neuropathy Rat's Model: An Untargeted Metabolomic Profiling and Correlation Study.International journal of molecular sciences · 2025Article
- Redox and Bioenergetic Modulation by Acacetin Attenuated Neuropathic Allodynia in Mice with Diet-induced Diabetes.Molecular neurobiology · 2025Article
- Muscarinic Receptor Antagonism and TRPM3 Activation as Stimulators of Mitochondrial Function and Axonal Repair in Diabetic Sensorimotor Polyneuropathy.International journal of molecular sciences · 2025Review
- Mitochondrial dynamics in diabetic peripheral neuropathy: Pathogenesis, progression, and therapeutic approaches.Medicine · 2025Review
- Potassium/Sodium Citrate Attenuates Paclitaxel-Induced Peripheral Neuropathy.International journal of molecular sciences · 2025Article
- Gut microbial-derived phenylacetylglutamine accelerates host cellular senescence.Nature aging · 2025Article
- Collaborative Roles for RAC1, ERM Proteins and PTEN During Adult Sensory Axon Regeneration.Molecular neurobiology · 2025Article
- Drug repurposing for hard-to-treat human alveolar echinococcosis: pyronaridine and beyond.Parasitology · 2024Article
- Investigating the interplay between mitophagy and diabetic neuropathy: Uncovering the hidden secrets of the disease pathology.Pharmacological research · 2024Review
- Targeting the muscarinic M1 receptor with a selective, brain-penetrant antagonist to promote remyelination in multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Centralizing the Knowledge and Interpretation of Pain in Chemotherapy-Induced Peripheral Neuropathy: A Paradigm Shift towards Brain-Centric Approaches.Brain sciences · 2024Review
- Improvement of diabetes-induced spinal cord axon injury with taurine via nerve growth factor-dependent Akt/mTOR pathway.Amino acids · 2024Article
- Vincamine as an agonist of G-protein-coupled receptor 40 effectively ameliorates diabetic peripheral neuropathy in mice.Acta pharmacologica Sinica · 2023Article
- Exploring Cholinergic Compounds for Peripheral Neuropathic Pain Management: A Comprehensive Scoping Review of Rodent Model Studies.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Abnormal Intraepidermal Nerve Fiber Density in Disease: A Scoping Review.medRxiv : the preprint server for health sciences · 2023Article
- Abnormal intraepidermal nerve fiber density in disease: A scoping review.Frontiers in neurology · 2023Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
Abstract
Sensory neurons have the capacity to produce, release, and respond to acetylcholine (ACh), but the functional role of cholinergic systems in adult mammalian peripheral sensory nerves has not been established. Here, we have reported that neurite outgrowth from adult sensory neurons that were maintained under subsaturating neurotrophic factor conditions operates under cholinergic constraint that is mediated by muscarinic receptor-dependent regulation of mitochondrial function via AMPK. Sensory neurons from mice lacking the muscarinic ACh type 1 receptor (M1R) exhibited enhanced neurite outgrowth, confirming the role of M1R in tonic suppression of axonal plasticity. M1R-deficient mice made diabetic with streptozotocin were protected from physiological and structural indices of sensory neuropathy. Pharmacological blockade of M1R using specific or selective antagonists, pirenzepine, VU0255035, or muscarinic toxin 7 (MT7) activated AMPK and overcame diabetes-induced mitochondrial dysfunction in vitro and in vivo. These antimuscarinic drugs prevented or reversed indices of peripheral neuropathy, such as depletion of sensory nerve terminals, thermal hypoalgesia, and nerve conduction slowing in diverse rodent models of diabetes. Pirenzepine and MT7 also prevented peripheral neuropathy induced by the chemotherapeutic agents dichloroacetate and paclitaxel or HIV envelope protein gp120. As a variety of antimuscarinic drugs are approved for clinical use against other conditions, prompt translation of this therapeutic approach to clinical trials is feasible.
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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.