ArticleThe journal of pain2016
Pioglitazone Inhibits the Development of Hyperalgesia and Sensitization of Spinal Nociresponsive Neurons in Type 2 Diabetes.
Article in The journal of pain, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Exploring the efficacy of plant-based nutraceuticals in managing diabetic neuropathy.Inflammopharmacology · 2025Pooled it
- New pharmacological agents and emerging therapeutic targets for painful diabetic neuropathy.Frontiers in endocrinology · 2026Review
- Long-lasting and fast methylglyoxal-scavenging peptide CycK(Myr)RPain reports · 2025Article
- New PPARα Agonist A190-Loaded Microemulsion for Chemotherapy-Induced Peripheral Neuropathy.Molecular pharmaceutics · 2025Article
- Single-cell analysis of dorsal root ganglia reveals metalloproteinase signaling in satellite glial cells and pain.Brain, behavior, and immunity · 2023Article
- Peroxisome proliferator-activated receptor gamma agonist ELB00824 suppresses oxaliplatin-induced pain, neuronal hypersensitivity, and oxidative stress.Neuropharmacology · 2022Article
- Peripheral Neuropathy Phenotyping in Rat Models of Type 2 Diabetes Mellitus: Evaluating Uptake of the Neurodiab Guidelines and Identifying Future Directions.Diabetes & metabolism journal · 2022Review
- The PPARγ agonist pioglitazone produces a female-predominant inhibition of hyperalgesia associated with surgical incision, peripheral nerve injury, and painful diabetic neuropathy.Neuropharmacology · 2022Article
- Therapeutic Potential of Polyphenols in the Management of Diabetic Neuropathy.Evidence-based complementary and alternative medicine : eCAM · 2021Review
- Metformin Preserves Peripheral Nerve Damage with Comparable Effects to Alpha Lipoic Acid in Streptozotocin/High-Fat Diet Induced Diabetic Rats.Diabetes & metabolism journal · 2020Article
- Lipid metabolism adaptations are reduced in human compared to murine Schwann cells following injury.Nature communications · 2020Article
- Building and Testing PPARγ Therapeutic ELB00824 with an Improved Therapeutic Window for Neuropathic Pain.Molecules (Basel, Switzerland) · 2020Review
- Polyphenols for diabetes associated neuropathy: Pharmacological targets and clinical perspective.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2019Review
- Article
- Sexual Dimorphism of Pain Control: Analgesic Effects of Pioglitazone and Azithromycin in Chronic Spinal Cord Injury.Journal of neurotrauma · 2019Article
- Methylglyoxal and a spinal TRPA1-AC1-Epac cascade facilitate pain in the db/db mouse model of type 2 diabetes.Neurobiology of disease · 2019Article
- PPARs and pain.British journal of pharmacology · 2019Review
- 3-Mercapto-5H-1,2,4-Triazino[5,6-b]Indole-5-Acetic Acid (Cemtirestat) Alleviates Symptoms of Peripheral Diabetic Neuropathy in Zucker Diabetic Fatty (ZDF) Rats: A Role of Aldose Reductase.Neurochemical research · 2019Article
- Article
- Effects of Dual Peroxisome Proliferator-Activated ReceptorsPPAR research · 2019Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledThiazolidinedione drugs (TZDs) such as pioglitazone are approved by the U.S. Food and Drug Administration for the treatment of insulin resistance in type 2 diabetes. However, whether TZDs reduce painful diabetic neuropathy (PDN) remains unknown. Therefore, we tested the hypothesis that chronic administration of pioglitazone would reduce PDN in Zucker Diabetic Fatty (ZDF(fa/fa) [ZDF]) rats. Compared with Zucker Lean (ZL(fa/+)) controls, ZDF rats developed: (1) increased blood glucose, hemoglobin A1c, methylglyoxal, and insulin levels; (2) mechanical and thermal hyperalgesia in the hind paw; (3) increased avoidance of noxious mechanical probes in a mechanical conflict avoidance behavioral assay, to our knowledge, the first report of a measure of affective-motivational pain-like behavior in ZDF rats; and (4) exaggerated lumbar dorsal horn immunohistochemical expression of pressure-evoked phosphorylated extracellular signal-regulated kinase. Seven weeks of pioglitazone (30 mg/kg/d in food) reduced blood glucose, hemoglobin A1c, hyperalgesia, and phosphorylated extracellular signal-regulated kinase expression in ZDF. To our knowledge, this is the first report to reveal hyperalgesia and spinal sensitization in the same ZDF animals, both evoked by a noxious mechanical stimulus that reflects pressure pain frequently associated with clinical PDN. Because pioglitazone provides the combined benefit of reducing hyperglycemia, hyperalgesia, and central sensitization, we suggest that TZDs represent an attractive pharmacotherapy in patients with type 2 diabetes-associated pain. PERSPECTIVE: To our knowledge, this is the first preclinical report to show that: (1) ZDF rats exhibit hyperalgesia and affective-motivational pain concurrent with central sensitization; and (2) pioglitazone reduces hyperalgesia and spinal sensitization to noxious mechanical stimulation within the same subjects. Further studies are needed to determine the anti-PDN effect of TZDs in humans.
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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.