ArticleNeuroscience bulletin2014
Extracellular signal-regulated protein kinase activation in spinal cord contributes to pain hypersensitivity in a mouse model of type 2 diabetes.
Article in Neuroscience bulletin, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 31 citations in OpenAlex.
- Monoclonal antibodies inhibiting MMP-9 activity alleviate peripheral neuropathy in diabetic mice.Science translational medicine · 2026Article
- Targeting druggable kinases in neuropathic pain.npj drug discovery · 2026Review
- Role of astrocytes in diabetic neuropathy: Review of their involvement in disease mechanisms.World journal of diabetes · 2025Review
- Long-lasting and fast methylglyoxal-scavenging peptide CycK(Myr)RPain reports · 2025Article
- Translating Basic Science to Clinical Applications: A Narrative Review of Repurposed Pharmacological Agents in Preclinical Models of Diabetic Neuropathy.Biomedicines · 2025Review
- RNA Interference Unleashed: Current Perspective of Small Interfering RNA (siRNA) Therapeutics in the Treatment of Neuropathic Pain.ACS pharmacology & translational science · 2024Review
- Glial cell alterations in diabetes-induced neurodegeneration.Cellular and molecular life sciences : CMLS · 2024Review
- Protein Kinase C (PKC)-mediated TGF-β Regulation in Diabetic Neuropathy: Emphasis on Neuro-inflammation and Allodynia.Endocrine, metabolic & immune disorders drug targets · 2024Review
- Neuroinflammation Involved in Diabetes-Related Pain and Itch.Frontiers in pharmacology · 2022Review
- Neuropathic Pain: Biomolecular Intervention and Imaging via Targeting Microglia Activation.Biomolecules · 2021Review
- SP6616 as a Kv2.1 inhibitor efficiently ameliorates peripheral neuropathy in diabetic mice.EBioMedicine · 2020Article
- Resolvins: Potent Pain Inhibiting Lipid Mediators via Transient Receptor Potential Regulation.Frontiers in cell and developmental biology · 2020Review
- Methylglyoxal and a spinal TRPA1-AC1-Epac cascade facilitate pain in the db/db mouse model of type 2 diabetes.Neurobiology of disease · 2019Article
- Pretreatment with AM1241 Enhances the Analgesic Effect of Intrathecally Administrated Mesenchymal Stem Cells.Stem cells international · 2019Article
- Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in mice.Scientific reports · 2018Article
- Sex-Dependent Glial Signaling in Pathological Pain: Distinct Roles of Spinal Microglia and Astrocytes.Neuroscience bulletin · 2018Article
- The Inhibitory Effects of Cobalt Protoporphyrin IX and Cannabinoid 2 Receptor Agonists in Type 2 Diabetic Mice.International journal of molecular sciences · 2017Article
- The induction of the transcription factor Nrf2 enhances the antinociceptive effects of delta-opioid receptors in diabetic mice.PloS one · 2017Article
- Methylglyoxal Requires AC1 and TRPA1 to Produce Pain and Spinal Neuron Activation.Frontiers in neuroscience · 2017Article
- Interferon alpha inhibits spinal cord synaptic and nociceptive transmission via neuronal-glial interactions.Scientific reports · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Painful peripheral neuropathy is a common complication of diabetes mellitus. The symptom of pain can become a major factor that decreases the quality of life of patients with diabetes, while effective treatment is lacking. In the present study, we aimed to investigate the changes of pain threshold in the early stage of diabetes in db/db mice, an animal model of type 2 diabetes mellitus, and the underlying molecular mechanisms. We found that (1) db/db mice (with a leptin receptor-null mutation and characterized by obesity and hyperglycemia) showed hypersensitivity to mechanical and thermal stimuli at the early stage of diabetes; (2) phosphorylated extracellular signal-regulated kinase (pERK), but not total ERK in the spinal cord and dorsal root ganglia in db/db mice significantly increased compared with wild-type mice. The increased pERK immunoreactivity occurred in both NeuN-expressing neurons and GFAP-expressing astrocytes, but not in Iba-1-expressing microglia; (3) both single and consecutive (for 5 days) intrathecal injections of U0126 (2 nmol per day), a selective MEK (an ERK kinase) inhibitor beginning at 8 weeks of age, attenuated the bilateral mechanical allodynia in the von-Frey test and heat hyperalgesia in Hargreave's test; and (4) db/db mice also displayed increased nocifensive behavior during the formalin test, and this was blocked by intrathecal injection of U0126. Also, the expression of pERK1 and pERK2 was upregulated following the formalin injection. Our results suggested that the activation of ERK in spinal neurons and astrocytes is correlated with pain hypersensitivity of the type 2 diabetes animal model. Inhibiting the ERK pathway may provide a new therapy for pain control in type 2 diabetes.
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.