ArticleNeurobiology of disease2012
Nerve growth factor/p38 signaling increases intraepidermal nerve fiber densities in painful neuropathy of type 2 diabetes.
Article in Neurobiology of disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 53 citations in OpenAlex.
- Dietary monounsaturated fatty acids reduce nerve inflammation and improve nerve function in murine models of obesity.Frontiers in immunology · 2026Article
- Dynamic transcriptomic profiling of dorsal root ganglia reveals stage-specific mechanisms in diabetic neuropathic pain.Frontiers in molecular neuroscience · 2026Article
- Intraepidermal Nerve Fiber Quantification of the Mouse Hind Paw Footpads: A Detailed and Simplified Protocol.Bio-protocol · 2025Article
- Synergistic effects of PAR2 and TrkA exacerbate visceral hypersensitivity induced by chronic pancreatitis in rats.IBRO neuroscience reports · 2025Article
- Nerve Growth Factor in Diabetes Mellitus: Pathophysiological Mechanisms, Biomarkers and Therapeutic Opportunities.Pharmaceuticals (Basel, Switzerland) · 2025Review
- NGF in Neuropathic Pain: Understanding Its Role and Therapeutic Opportunities.Current issues in molecular biology · 2025Review
- The analgesic effect of paeoniflorin: A focused review.Open life sciences · 2024Review
- Transcriptomic analysis of diabetic kidney disease and neuropathy in mouse models of type 1 and type 2 diabetes.Disease models & mechanisms · 2023Article
- Dietary interventions improve diabetic kidney disease, but not peripheral neuropathy, in a db/db mouse model of type 2 diabetes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Netrin-3 Suppresses Diabetic Neuropathic Pain by Gating the Intra-epidermal Sprouting of Sensory Axons.Neuroscience bulletin · 2023Article
- Treatment for Diabetic Peripheral Neuropathy: What have we Learned from Animal Models?Current diabetes reviews · 2022Review
- Neuronal Inflammation is Associated with Changes in Epidermal Innervation in High Fat Fed Mice.Frontiers in physiology · 2022Article
- An Insight into Potential Pharmacotherapeutic Agents for Painful Diabetic Neuropathy.Journal of diabetes research · 2022Review
- Monoclonal Antibodies for Chronic Pain Treatment: Present and Future.International journal of molecular sciences · 2021Review
- Sex-related differences in response to masseteric injections of glutamate and nerve growth factor in healthy human participants.Scientific reports · 2021Article
- Differential effects of minocycline on microvascular complications in murine models of type 1 and type 2 diabetes.Journal of translational science · 2021Article
- Nerve and Vascular Biomarkers in Skin Biopsies Differentiate Painful From Painless Peripheral Neuropathy in Type 2 Diabetes.Frontiers in pain research (Lausanne, Switzerland) · 2021Article
- Upregulation of miR-133a-3p in the Sciatic Nerve Contributes to Neuropathic Pain Development.Molecular neurobiology · 2020Article
- Interleukin-10 Reduces Neurogenic Inflammation and Pain Behavior in a Mouse Model of Type 2 Diabetes.Journal of pain research · 2020Article
- Toll-like receptors and inflammation in metabolic neuropathy; a role in early versus late disease?Experimental neurology · 2019Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Painful diabetic neuropathy (PDN) is a common, yet devastating complication of type 2 diabetes. At this time, there is no objective test for diagnosing PDN. In the current study, we measured the peptidergic intraepidermal nerve fiber densities (IENFD) from hind paws of the db/db mouse, an animal model for type 2 diabetes, during the period of mechanical allodynia from 6 to 12 weeks of age. Intraepidermal nerve fibers (IENF) of the hind footpads were identified by protein gene product (PGP) 9.5 immunohistochemistry. The peptidergic IENF were determined by double immunofluorescence using anti-PGP9.5 and antibodies against tropomyosin-receptor-kinase (Trk) A. We observed a significant increase in PGP9.5-positive IENFD at 8 and 10 weeks of age. Similarly, Trk A-positive peptidergic IENF, which also express substance P and calcitonin gene related peptide in db/db mice, were observed to be elevated from 1.5 to 2 fold over controls. This upregulation ended at 16 weeks of age, in accordance with the reduction of mechanical allodynia. Anti-NGF treatment significantly inhibited the upregulation of peptidergic IENFD during the period of mechanical allodynia, suggesting that increased neurotrophism may mediate this phenomenon. In addition, SB203580, an inhibitor of p38, blocked the increase in peptidergic IENFD in db/db mice. The current results suggest that peptidergic IENFD could be a potential diagnostic indicator for PDN in type 2 diabetes. Furthermore, the inhibition of NGF-p38 signaling could be a potential therapeutic strategy for treating this painful condition.
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