ArticlePloS one2014
Neurostimulation of the cholinergic anti-inflammatory pathway ameliorates disease in rat collagen-induced arthritis.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 110 papers, 1 of them a synthesis that pooled it.
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.
A Pilot Study to Quantify the Autonomic Nervous System Balance in Healthy, Able-Bodied Individuals
Effect of Perioperative Neurostimulation in Patients Undergoing Whipple Operation (Pancreaticoduodenectomy) on Acute Postsurgical Inflammatory Response [ENSWAPI-trial]
Who cites it
110 citing papers in PubMed, 1 synthesis or guideline pooled it, 197 citations in OpenAlex.
- Assessing the therapeutic potential of vagus nerve stimulation in autoimmune diseases: A systematic review.Physiological reports · 2025Pooled it
- Sacral nerve stimulation modulates disease activity and autonomic function in active rheumatoid arthritis: a randomized pilot study.Clinical rheumatology · 2026Trial
- Vagus nerve-mediated neuroimmune modulation for rheumatoid arthritis: a pivotal randomized controlled trial.Nature medicine · 2026Trial
- The Cholinergic Drug Galantamine Alleviates Oxidative Stress Alongside Anti-inflammatory and Cardio-Metabolic Effects in Subjects With the Metabolic Syndrome in a Randomized Trial.Frontiers in immunology · 2021Trial
- Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis.Proceedings of the National Academy of Sciences of the United States of America · 2016Trial
- Transvenous vagus nerve stimulation does not modulate the innate immune response during experimental human endotoxemia: a randomized controlled study.Arthritis research & therapy · 2015Trial
- The Vagus Nerve-Macrophage Connection: Tuning the Rheostat of Regenerative Medicine.International journal of molecular sciences · 2026Review
- Closed-Loop Neuromodulation for Brain Fatigue: From Real-Time Biomarkers to Adaptive Intervention.International journal of molecular sciences · 2026Review
- Review
- Vagus nerve stimulation in Crohn's disease: long-term outcomes, mechanistic insights, and the promise of non-invasive approaches.Bioelectronic medicine · 2026Article
- The roles of the nerve-immune axis in modulating bone regeneration.Bone research · 2026Review
- The brain-gut-joint axis in arthritis: crosstalk, treatment, and future perspectives.Journal of orthopaedic translation · 2026Review
- Neuroimmune Modulation for Drug-Refractory Rheumatoid Arthritis: Long-Term Safety and Efficacy in Patients Enrolled in a Pilot Vagus Nerve Stimulation Study.Rheumatology and therapy · 2025Article
- Neuroimmune Control of Inflammation in Acute Kidney Injury and Multiorgan Dysfunction.Journal of the American Society of Nephrology : JASN · 2025Review
- Article
- Gut-specific histamine 3 receptor signaling orchestrates microglia-dependent resolution of peripheral inflammation.The Journal of clinical investigation · 2025Article
- Autonomic Nervous System in Bone Remodeling: From Mechanisms to Novel Therapies in Orthopedic Diseases.Orthopaedic surgery · 2025Review
- Scaling of vagus nerve stimulation parameters does not achieve equivalent nerve responses across species.Bioelectronic medicine · 2025Article
- Macrophages as central mediators of sympathetic neuro-immune interplay in autoimmunity.Frontiers in immunology · 2025Review
- Physiopathological Roles of White Adiposity and Gut Functions in Neuroinflammation.International journal of molecular sciences · 2024Review
50 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThe inflammatory reflex is a physiological mechanism through which the nervous system maintains immunologic homeostasis by modulating innate and adaptive immunity. We postulated that the reflex might be harnessed therapeutically to reduce pathological levels of inflammation in rheumatoid arthritis by activating its prototypical efferent arm, termed the cholinergic anti-inflammatory pathway. To explore this, we determined whether electrical neurostimulation of the cholinergic anti-inflammatory pathway reduced disease severity in the collagen-induced arthritis model.
methodsRats implanted with vagus nerve cuff electrodes had collagen-induced arthritis induced and were followed for 15 days. Animals underwent active or sham electrical stimulation once daily from day 9 through the conclusion of the study. Joint swelling, histology, and levels of cytokines and bone metabolism mediators were assessed.
resultsCompared with sham treatment, active neurostimulation of the cholinergic anti-inflammatory pathway resulted in a 52% reduction in ankle diameter (p = 0.02), a 57% reduction in ankle diameter (area under curve; p = 0.02) and 46% reduction overall histological arthritis score (p = 0.01) with significant improvements in inflammation, pannus formation, cartilage destruction, and bone erosion (p = 0.02), accompanied by numerical reductions in systemic cytokine levels, not reaching statistical significance. Bone erosion improvement was associated with a decrease in serum levels of receptor activator of NF-κB ligand (RANKL) from 132±13 to 6±2 pg/mL (mean±SEM, p = 0.01).
conclusionsThe severity of collagen-induced arthritis is reduced by neurostimulation of the cholinergic anti-inflammatory pathway delivered using an implanted electrical vagus nerve stimulation cuff electrode, and supports the rationale for testing this approach in human inflammatory disorders.
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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.