ArticlePain2014
Multiple roles for NaV1.9 in the activation of visceral afferents by noxious inflammatory, mechanical, and human disease-derived stimuli.
Article in Pain, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- Systematic Review on Herbal Preparations for Controlling Visceral Hypersensitivity in Functional Gastrointestinal Disorders.Current pharmaceutical biotechnology · 2024Pooled it
- Mechanisms of chronic abdominal pain in inflammatory bowel disease and implications for treatment.Nature reviews. Gastroenterology & hepatology · 2026Review
- Sculpting excitable membranes: voltage-gated ion channel delivery and distribution.Nature reviews. Neuroscience · 2025Review
- Article
- Visceral Pain in Preterm Infants with Necrotizing Enterocolitis: Underlying Mechanisms and Implications for Treatment.Paediatric drugs · 2025Review
- Article
- The influence of Nav1.9 channels on intestinal hyperpathia and dysmotility.Channels (Austin, Tex.) · 2023Review
- Article
- Inflammation differentially controls transport of depolarizing Nav versus hyperpolarizing Kv channels to drive rat nociceptor activity.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Role of NaThe Journal of physiology · 2023Article
- The potential for NaThe Journal of physiology · 2023Article
- Paclitaxel effects on axonal localization and vesicular trafficking of NaFrontiers in molecular neuroscience · 2023Article
- Fibroblast growth factor homologous factor 2 attenuates excitability of DRG neurons.Journal of neurophysiology · 2022Article
- Novel Therapies for the Treatment of Neuropathic Pain: Potential and Pitfalls.Journal of clinical medicine · 2022Review
- Familial Episodic Pain Syndromes.Journal of pain research · 2022Review
- Post-inflammatory Abdominal Pain in Patients with Inflammatory Bowel Disease During Remission: A Comprehensive Review.Crohn's & colitis 360 · 2021Review
- Paclitaxel increases axonal localization and vesicular trafficking of Nav1.7.Brain : a journal of neurology · 2021Article
- The physiological function of different voltage-gated sodium channels in pain.Nature reviews. Neuroscience · 2021Review
- Stimulus intensity-dependent recruitment of NaAmerican journal of physiology. Gastrointestinal and liver physiology · 2020Article
- Enteric Glia Modulate Macrophage Phenotype and Visceral Sensitivity following Inflammation.Cell reports · 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
16 authors at 4 institutions in 1 country.
Funding
Abstract
Chronic visceral pain affects millions of individuals worldwide and remains poorly understood, with current therapeutic options constrained by gastrointestinal adverse effects. Visceral pain is strongly associated with inflammation and distension of the gut. Here we report that the voltage-gated sodium channel subtype NaV1.9 is expressed in half of gut-projecting rodent dorsal root ganglia sensory neurons. We show that NaV1.9 is required for normal mechanosensation, for direct excitation and for sensitization of mouse colonic afferents by mediators from inflammatory bowel disease tissues, and by noxious inflammatory mediators individually. Excitatory responses to ATP or PGE2 were substantially reduced in NaV1.9(-/-) mice. Deletion of NaV1.9 substantially attenuates excitation and subsequent mechanical hypersensitivity after application of inflammatory soup (IS) (bradykinin, ATP, histamine, PGE2, and 5HT) to visceral nociceptors located in the serosa and mesentery. Responses to mechanical stimulation of mesenteric afferents were also reduced by loss of NaV1.9, and there was a rightward shift in stimulus-response function to ramp colonic distension. By contrast, responses to rapid, high-intensity phasic distension of the colon are initially unaffected; however, run-down of responses to repeat phasic distension were exacerbated in NaV1.9(-/-) afferents. Finally colonic afferent activation by supernatants derived from inflamed human tissue was greatly reduced in NaV1.9(-/-) mice. These results demonstrate that NaV1.9 is required for persistence of responses to intense mechanical stimulation, contributes to inflammatory mechanical hypersensitivity, and is essential for activation by noxious inflammatory mediators, including those from diseased human bowel. These observations indicate that NaV1.9 represents a high-value target for development of visceral analgesics.
Indexed as
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.