ArticleDiabetologia2008
Inducible nitric oxide synthase gene deficiency counteracts multiple manifestations of peripheral neuropathy in a streptozotocin-induced mouse model of diabetes.
Article in Diabetologia, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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
42 citing papers in PubMed, 86 citations in OpenAlex.
- Diabetic neuropathy: cutting-edge research and future directions.Signal transduction and targeted therapy · 2025Review
- Diabetic Neuropathy: An Overview of Molecular Pathways and Protective Mechanisms of Phytobioactives.Endocrine, metabolic & immune disorders drug targets · 2024Review
- Melatonin Mitigates iNOS-Related Effects of HEMA and Camphorquinone in Human Dental Pulp Cells: Relevance for Postoperative Sensitivity Mechanism in Type 2 Diabetes.International journal of molecular sciences · 2023Article
- The Predictive Value of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio Levels of Diabetic Peripheral Neuropathy.Journal of pain research · 2021Article
- Diabetic neuropathy research: from mouse models to targets for treatment.Neural regeneration research · 2019Review
- Neurons and Microglia; A Sickly-Sweet Duo in Diabetic Pain Neuropathy.Frontiers in neuroscience · 2019Review
- Nitrosative damage during retrovirus infection-induced neuropathic pain.Journal of neuroinflammation · 2018Article
- Article
- Association of myelinated primary afferents impairment with mechanical allodynia in diabetic peripheral neuropathy: an experimental study in rats.Oncotarget · 2017Article
- Small-molecule inhibition of STOML3 oligomerization reverses pathological mechanical hypersensitivity.Nature neuroscience · 2017Article
- Wound Healing Delay in the ZDSD Rat.In vivo (Athens, Greece) · 2017Article
- Role of Transient Receptor Potential Channels Trpv1 and Trpm8 in Diabetic Peripheral Neuropathy.Journal of diabetes and treatment · 2017Article
- Gene Expression Profiling Identifies Downregulation of the Neurotrophin-MAPK Signaling Pathway in Female Diabetic Peripheral Neuropathy Patients.Journal of diabetes research · 2017Article
- Article
- Oxidative and nitrative stress in neurodegeneration.Neurobiology of disease · 2015Review
- Potential role of nitric oxide synthase isoforms in pathophysiology of neuropathic pain.Inflammopharmacology · 2014Review
- Glucose-induced metabolic memory in Schwann cells: prevention by PPAR agonists.Endocrinology · 2013Article
- Cytokine modulation is necessary for efficacious treatment of experimental neuropathic pain.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2013Review
- Animal models of diabetic neuropathy: progress since 1960s.Journal of diabetes research · 2013Review
- Marrow-derived cells regulate the development of early diabetic retinopathy and tactile allodynia in mice.Diabetes · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
aims/hypothesisEvidence for the importance of peroxynitrite, a product of superoxide anion radical reaction with nitric oxide, in peripheral diabetic neuropathy is emerging. The role of specific nitric oxide synthase isoforms in diabetes-associated nitrosative stress and nerve fibre dysfunction and degeneration remains unknown. This study evaluated the contribution of inducible nitric oxide synthase (iNOS) to peroxynitrite injury to peripheral nerve and dorsal root ganglia and development of peripheral diabetic neuropathy.
methodsControl mice and mice with iNos (also known as Nos2) gene deficiency (iNos ( -/- )) were made diabetic with streptozotocin, and maintained for 6 weeks. Peroxynitrite injury was assessed by nitrotyrosine and poly(ADP-ribose) accumulation (immunohistochemistry). Thermal algesia was evaluated by paw withdrawal, tail-flick and hot plate tests, mechanical algesia by the Randall-Selitto test, and tactile allodynia by a von Frey filament test.
resultsDiabetic wild-type mice displayed peroxynitrite injury in peripheral nerve and dorsal root ganglion neurons. They also developed motor and sensory nerve conduction velocity deficits, thermal and mechanical hypoalgesia, tactile allodynia and approximately 36% loss of intraepidermal nerve fibres. Diabetic iNos ( -/- ) mice did not display nitrotyrosine and poly(ADP-ribose) accumulation in peripheral nerve, but were not protected from nitrosative stress in dorsal root ganglia. Despite this latter circumstance, diabetic iNos ( -/- ) mice preserved normal nerve conduction velocities. Small-fibre sensory neuropathy was also less severe in diabetic iNos ( -/- ) than in wild-type mice. CONCLUSIONS/
interpretationiNOS plays a key role in peroxynitrite injury to peripheral nerve, and functional and structural changes of diabetic neuropathy. Nitrosative stress in axons and Schwann cells, rather than dorsal root ganglion neurons, underlies peripheral nerve dysfunction and degeneration.
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.