ArticleEuropean journal of pain (London, England)2017
Blockade of sigma 1 receptors alleviates sensory signs of diabetic neuropathy in rats.
Article in European journal of pain (London, England), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 25 citations in OpenAlex.
- Diabetic neuropathy: cutting-edge research and future directions.Signal transduction and targeted therapy · 2025Review
- Preclinical Evaluation of Sigma 1 Receptor Antagonists as a Novel Treatment for Painful Diabetic Neuropathy.ACS pharmacology & translational science · 2024Article
- Review
- Review
- Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioids.Acta pharmaceutica Sinica. B · 2023Article
- Article
- 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
- Sigma-1 Receptor Inhibition Reduces Neuropathic Pain Induced by Partial Sciatic Nerve Transection in Mice by Opioid-Dependent and -Independent Mechanisms.Frontiers in pharmacology · 2019Article
- Repeated Sigma-1 Receptor Antagonist MR309 Administration Modulates Central Neuropathic Pain Development After Spinal Cord Injury in Mice.Frontiers in pharmacology · 2019Article
- Characterization of Cardiovascular Alterations Induced by Different Chronic Cisplatin Treatments.Frontiers in pharmacology · 2017Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundE-52862 (S1RA, 4-[2-[[5-methyl-1-(2-naphthalenyl)-1H-pyrazol-3-yl]oxy]ethyl]-morpholine), a novel selective sigma 1 receptor (σ1R) antagonist, has demonstrated efficacy in nociceptive and neuropathic pain models. Our aim was to test if σ1R blockade with E-52862 may modify the signs of neuropathy in Zucker diabetic fatty (ZDF) rats, a type 2 diabetes model.
methodsMechanical and thermal response thresholds were tested on 7-, 13-, 14- and 15-week-old ZDF rats treated with saline or with E-52862 acutely administered on week 13, followed by sub-chronic administration (14 days). Axonal peripheral activity (skin-saphenous nerve preparation) and isolated aorta or mesenteric bed reactivity were analysed in 15-week-old ZDF rats treated with saline or E-52862 and in LEAN rats.
resultsZucker diabetic fatty rats showed significantly decreased thermal withdrawal latency and threshold to mechanical stimulation on week 13 compared to week 7 (prediabetes) and with LEAN animals; single-dose and sub-chronic E-52862 administration restored both parameters to those recorded on week 7. Regarding axonal peripheral activity, E-52862 treatment increased the mean mechanical threshold (77.3 ± 21 mN vs. 19.6 ± 1.5 mN, saline group) and reduced the response evoked by mechanical increasing stimulation (86.4 ± 36.5 vs. 352.8 ± 41.4 spikes) or by repeated mechanical supra-threshold steps (39.4 ± 1.4 vs. 83.5 ± 0.9). E-52862 treatment also restored contractile response to phenylephrine in aorta and mesenteric bed.
conclusionsE-52862 administration reverses neuropathic (behavioural and electrophysiological) and vascular signs in the ZDF rat. SIGNIFICANCE: Blockade of σ1R avoids the development of diabetic neuropathy in rats, and may represent a potentially useful therapeutic approach to peripheral neuropathies in diabetic patients. WHAT DOES THIS STUDY ADD?: This study presents evidences for the potential usefulness of sigma receptor blockade on diabetic neuropathy in rats. The methodology includes behavioural evidences, electrophysiological data and vascular-isolated models.
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