New perspectives on the management of diabetic peripheral neuropathic pain

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.SignificanceBlockade 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.

show abstract

“…Current treatments are only partially effective and, at best, provide 50% pain relief in one‐third of patients (Jensen et al., 2006). …”

Section: Introductionmentioning

confidence: 99%

Blockade of sigma 1 receptors alleviates sensory signs of diabetic neuropathy in rats

Paniagua

Girón

Goicoechea

et al. 2016

European Journal of Pain

View full text Add to dashboard Cite

show abstract

“…Additional risk factors for diabetic neuropathic pain have been proposed, including smoking, hypertension, obesity, hypercholesterolaemia and duration of diabetes (Tesfaye et al., 2005; Jensen et al., 2006). Epidemiological studies can identify risk factors and effective preventive strategies in parallel with the search for the underlying causative biological mechanisms, such as genetic pathways (Smith et al., 2007).…”

Section: Introductionmentioning

confidence: 99%

A genome‐wide association study suggests an association of Chr8p21.3 (GFRA2) with diabetic neuropathic pain

Wang

Deshmukh

Zuydam

et al. 2015

European Journal of Pain

View full text Add to dashboard Cite

BackgroundNeuropathic pain, caused by a lesion or a disease affecting the somatosensory system, is one of the most common complications in diabetic patients. The purpose of this study is to identify genetic factors contributing to this type of pain in a general diabetic population.MethodWe accessed the Genetics of Diabetes Audit and Research Tayside (GoDARTS) datasets that contain prescription information and monofilament test results for 9439 diabetic patients, among which 6927 diabetic individuals were genotyped by Affymetrix SNP6.0 or Illumina OmniExpress chips. Cases of neuropathic pain were defined as diabetic patients with a prescription history of at least one of five drugs specifically indicated for the treatment of neuropathic pain and in whom monofilament test result was positive for sensory neuropathy in at least one foot. Controls were individuals who did not have a record of receiving any opioid analgesics. Imputation of non‐genotyped SNPs was performed by IMPUTE2, with reference files from 1000 Genomes Phase I datasets.ResultsAfter data cleaning and relevant exclusions, imputed genotypes of 572 diabetic neuropathic pain cases and 2491 diabetic controls were used in the Fisher's exact test. We identified a cluster in the Chr8p21.3, next to GFRA2 with a lowest p‐value of 1.77 × 10−7 at rs17428041. The narrow‐sense heritability of this phenotype was 11.00%.ConclusionThis genome‐wide association study on diabetic neuropathic pain suggests new evidence for the involvement of variants near GFRA2 with the disorder, which needs to be verified in an independent cohort and at the molecular level.

show abstract

“…Semptomlara yönelik tedavi düzenle-nir. Çok yönlü bir tedavi planlaması gerektirir [26]. Hastalığın doğal seyri değişkendir.…”

Section: Discussionunclassified

Weakness of unilateral lower limb’s proximal muscle; diabetic amyotrophy coexisting with lumbar discopathy: Case report and review of the literature

Kurt¹

2014

Dicle Med J

View full text Add to dashboard Cite

Diabetic amyotrophy is a relatively infrequent complication of diabetes mellitus is most often characterized by weakness of unilateral lower limb and pain. Clinical differentiation from lumbar disc herniation may be difficult. ıt was hereby presented; 64 year old male patient who has 15 year old history of diabetes mellitus and lumbar discopathy previously diagnosed. He had weakness of unilateral lower limb and pain. Patient was admitted right thigh pain and weakness of proximal lower limb muscle. The physical examination, magnetic resonance imaging and electromyographic examination of the patient was consistent with the diagnosis of diabetic amyotrophy. When diabetic amyotrophy and lumbar disc herniaton coexist as a pain source, which disease responsible from pain should be detected well and treatments should be arrenged according to responsible disease. Thus, unnecessary surgeries can be avoided.Key words: Diabetes mellitus, lumbar disc herniation, diabetic amyotrophy ÖZET Diyabetin nadir bir komplikasyonu olan diyabetik amiyotrofi genellikle tek taraflı alt ekstremitede proksimal kas güçsüzlüğü ve ağrı ile seyreder. Klinik olarak lomber diskopatiden ayırımı zor olabilir. Bu olguda daha önce lomber diskopati tanısı konmuş ve 15 yıllık diyabetes mellitusu olan erkek hasta sunulmuştur. Hasta sağ uyluk bölgesinde ağrı, sağ alt ekstemite kas güçsüzlüğü şika-yeti polikliniğe başvurdu. Hastaya fizik muayene, manyetik rezonans görüntüleme ve elektrofizyolojik çalışmalar sonunda Diabetik amiyotrofi tanısı konulmuştur. Özellikle ağrı nedeni olarak lomber diskopti ve diyabetik amiyotrofi birlikteliğinde hastanın şikayetinin hangi hastalıktan kaynaklandığının iyi belirlenmesi ve tedavinin ona göre düzenlenmesi sağlanmalıdır. Böylece gereksiz cerrahi müdahaleden kaçınılmış olur.Anahtar kelimeler: Diyabet, lomber diskopati, diyabetik amiyotrofi GİRİŞ Diyabetik polinöropati (DPNP) diyabetes mellitusun (DM) sık komplikasyonlarından biridir. Kan glukoz düzeyinin yüksekliği ve hastalık süresi ile ilişkilidir [1,2]. Diyabetik amiyotrofi (DA), DP-NP'nin nadir bir formudur. Alt ekstremite proksimalinde akut veya subakut gelişen genellikle asimetrik güçsüzlük ve atrofi ile karakterizedir [3]. Lomber disk hernili (LDH) hastalarda da benzer şe-kilde tek taraflı veya her iki alt ekstremitede ağrı ve güçsüzlük gelişebilir. Diyabetli hastalar tek taraflı alt ekstremite ağrı ve güçsüzlüğü tariflediğinde DA ve LDH'nın ayırıcı tanısı zor olabilir [4,5,6]. Bu iki hastalığın ayırıcı tanısındaki zorluk sebebiyle hastalara gereksiz LDH cerrahisi uygulanabilir [4].Bu olguda lomber diskopati ve DA birlikteliği olan bir hastanın ayırıcı tanısı ve tedavi yaklaşımla-rı tartışılmıştır. OLGUAltmışdört yaşında 15 yıldır diyabetes mellitusun tanısı olan erkek hasta (A.Ö) 5 ay önce sağ bacağa yayılan bel ağrısı ve ayaklarda uyuşma şikayeti ile polikliniğimize başvurdu. Hastanın muayenesinde ,bel eklem hareket açıklığı; fleksiyonu sonlara doğ-ru ağrılı ve kısıtlı, diğer yönlere ağrılı ama açıktı.

show abstract

New perspectives on the management of diabetic peripheral neuropathic pain

Cited by 170 publications

References 78 publications

Blockade of sigma 1 receptors alleviates sensory signs of diabetic neuropathy in rats

Blockade of sigma 1 receptors alleviates sensory signs of diabetic neuropathy in rats

A genome‐wide association study suggests an association of Chr8p21.3 (GFRA2) with diabetic neuropathic pain

Weakness of unilateral lower limb’s proximal muscle; diabetic amyotrophy coexisting with lumbar discopathy: Case report and review of the literature

Contact Info

Product

Resources

About