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Complications
Pharmacological and Nonpharmacological Treatments for Painful Diabetic Peripheral Neuropathy
Han Na Jang, Tae Jung Oh
Diabetes Metab J. 2023;47(6):743-756.   Published online September 6, 2023
DOI: https://doi.org/10.4093/dmj.2023.0018
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AbstractAbstract PDFPubReader   ePub   
Diabetic peripheral neuropathy (DPN) is one of the most prevalent chronic complications of diabetes. The lifetime prevalence of DPN is thought to be >50%, and 15%–25% of patients with diabetes experience neuropathic pain, referred to as “painful DPN.” Appropriate treatment of painful DPN is important because this pain contributes to a poor quality of life by causing sleep disturbance, anxiety, and depression. The basic principle for the management of painful DPN is to control hyperglycemia and other modifiable risk factors, but these may be insufficient for preventing or improving DPN. Because there is no promising diseasemodifying medication for DPN, the pain itself needs to be managed when treating painful DPN. Drugs for neuropathic pain, such as gabapentinoids, serotonin–norepinephrine reuptake inhibitors, tricyclic antidepressants, alpha-lipoic acid, sodium channel blockers, and topical capsaicin, are used for the management of painful DPN. The U.S. Food and Drug Administration (FDA) has approved pregabalin, duloxetine, tapentadol, and the 8% capsaicin patch as drugs for the treatment of painful DPN. Recently, spinal cord stimulation using electrical stimulation is approved by the FDA for the treatment for painful DPN. This review describes the currently available pharmacological and nonpharmacological treatments for painful DPN.

Citations

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  • J-2156, a small molecule somatostatin type 4 receptor agonist, alleviated hindpaw hypersensitivity in the streptozotocin-induced rat model of painful diabetic neuropathy but with a 2-fold decrease in potency at an advanced stage in the model, mimicking mo
    A. Kuo, M. Z. Imam, R. Li, L. Lin, A. Raboczyj, A. E. Bohmer, J. R. Nicholson, L. Corradini, M. T. Smith
    Frontiers in Pharmacology.2024;[Epub]     CrossRef
  • The Chronic Wound–Related Pain Model
    Kevin Woo
    Clinics in Geriatric Medicine.2024;[Epub]     CrossRef
Short Communication
Technology/Device
Comparison of Laser and Conventional Lancing Devices for Blood Glucose Measurement Conformance and Patient Satisfaction in Diabetes Mellitus
Jung A Kim, Min Jeong Park, Eyun Song, Eun Roh, So Young Park, Da Young Lee, Jaeyoung Kim, Ji Hee Yu, Ji A Seo, Kyung Mook Choi, Sei Hyun Baik, Hye Jin Yoo, Nan Hee Kim
Diabetes Metab J. 2022;46(6):936-940.   Published online March 30, 2022
DOI: https://doi.org/10.4093/dmj.2021.0293
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  • 1 Web of Science
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AbstractAbstract PDFPubReader   ePub   
Self-monitoring of capillary blood glucose is important for controlling diabetes. Recently, a laser lancing device (LMT-1000) that can collect capillary blood without skin puncture was developed. We enrolled 150 patients with type 1 or 2 diabetes mellitus. Blood sampling was performed on the same finger on each hand using the LMT-1000 or a conventional lancet. The primary outcome was correlation between glucose values using the LMT-1000 and that using a lancet. And we compared the pain and satisfaction of the procedures. The capillary blood sampling success rates with the LMT-1000 and lancet were 99.3% and 100%, respectively. There was a positive correlation (r=0.974, P<0.001) between mean blood glucose levels in the LMT-1000 (175.8±63.0 mg/dL) and conventional lancet samples (172.5±63.6 mg/dL). LMT-1000 reduced puncture pain by 75.0% and increased satisfaction by 80.0% compared to a lancet. We demonstrated considerable consistency in blood glucose measurements between samples from the LMT-1000 and a lancet, but improved satisfaction and clinically significant pain reduction were observed with the LMT-1000 compared to those with a lancet.

Citations

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  • Comparison between a laser-lancing device and automatic incision lancet for capillary blood sampling from the heel of newborn infants: a randomized feasibility trial
    Chul Kyu Yun, Eui Kyung Choi, Hyung Jin Kim, Jaeyoung Kim, Byung Cheol Park, Kyuhee Park, Byung Min Choi
    Journal of Perinatology.2024;[Epub]     CrossRef
Original Article
Others
Increased Nociceptive Responses in Streptozotocin-Induced Diabetic Rats and the Related Expression of Spinal NR2B Subunit of N-Methyl-D-Aspartate Receptors
Che Aishah Nazariah Ismail, Rapeah Suppian, Che Badariah Abd Aziz, Khalilah Haris, Idris Long
Diabetes Metab J. 2019;43(2):222-235.   Published online November 19, 2018
DOI: https://doi.org/10.4093/dmj.2018.0020
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  • 12 Web of Science
  • 13 Crossref
AbstractAbstract PDFPubReader   
Background

This study investigated the role of NR2B in a modulated pain process in the painful diabetic neuropathy (PDN) rat using various pain stimuli.

Methods

Thirty-two Sprague-Dawley male rats were randomly allocated into four groups (n=8): control, diabetes mellitus (DM) rats and diabetic rats treated with ifenprodil at a lower dose (0.5 µg/day) (I 0.5) or higher dose (1.0 µg/day) (I 1.0). DM was induced by a single injection of streptozotocin at 60 mg/kg on day 0 of experimentation. Diabetic status was assessed on day 3 of the experimentation. The responses on both tactile and thermal stimuli were assessed on day 0 (baseline), day 14 (pre-intervention), and day 22 (post-intervention). Ifenprodil was given intrathecally for 7 days from day 15 until day 21. On day 23, 5% formalin was injected into the rats' hind paw and the nociceptive responses were recorded for 1 hour. The rats were sacrificed 72 hours post-formalin injection and an analysis of the spinal NR2B expression was performed.

Results

DM rats showed a significant reduction in pain threshold in response to the tactile and thermal stimuli and higher nociceptive response during the formalin test accompanied by the higher expression of phosphorylated spinal NR2B in both sides of the spinal cord. Ifenprodil treatment for both doses showed anti-allodynic and anti-nociceptive effects with lower expression of phosphorylated and total spinal NR2B.

Conclusion

We suggest that the pain process in the streptozotocin-induced diabetic rat that has been modulated is associated with the higher phosphorylation of the spinal NR2B expression in the development of PDN, which is similar to other models of neuropathic rats.

Citations

Citations to this article as recorded by  
  • Painful diabetic neuropathy: The role of ion channels
    Qi Wang, Yifei Ye, Linghui Yang, Lifan Xiao, Jin Liu, Wensheng Zhang, Guizhi Du
    Biomedicine & Pharmacotherapy.2024; 173: 116417.     CrossRef
  • Therapeutic potential of progesterone in spinal cord injury‐induced neuropathic pain: At the crossroads between neuroinflammation and N‐methyl‐D‐aspartate receptor
    Sol Ferreyra, Susana González
    Journal of Neuroendocrinology.2023;[Epub]     CrossRef
  • Chemical, pharmacodynamic and pharmacokinetic characterization of the GluN2B receptor antagonist 3-(4-phenylbutyl)-2,3,4,5-tetrahydro-1H-3-benzazepine-1,7-diol – starting point for PET tracer development
    Marvin Korff, Ruben Steigerwald, Elena Bechthold, Dirk Schepmann, Julian A. Schreiber, Sven G. Meuth, Guiscard Seebohm, Bernhard Wünsch
    Biological Chemistry.2023; 404(4): 279.     CrossRef
  • Mechanisms of Transmission and Processing of Pain: A Narrative Review
    Girolamo Di Maio, Ines Villano, Ciro Rosario Ilardi, Antonietta Messina, Vincenzo Monda, Ashlei Clara Iodice, Chiara Porro, Maria Antonietta Panaro, Sergio Chieffi, Giovanni Messina, Marcellino Monda, Marco La Marra
    International Journal of Environmental Research and Public Health.2023; 20(4): 3064.     CrossRef
  • Indazole as a Phenol Bioisostere: Structure–Affinity Relationships of GluN2B-Selective NMDA Receptor Antagonists
    Judith Lüken, Gunnar Goerges, Nadine Ritter, Paul Disse, Julian A. Schreiber, Judith Schmidt, Bastian Frehland, Dirk Schepmann, Guiscard Seebohm, Bernhard Wünsch
    Journal of Medicinal Chemistry.2023; 66(16): 11573.     CrossRef
  • Synthesis of oxazolo‐annulated 3‐benzazepines designed by merging two negative allosteric NMDA receptor modulators
    Alexander Markus, Dirk Schepmann, Bernhard Wünsch
    Archiv der Pharmazie.2022;[Epub]     CrossRef
  • Phenol—Benzoxazolone bioisosteres: Synthesis and biological evaluation of tricyclic GluN2B‐selective N‐methyl‐d‐aspartate receptor antagonists
    Alexander Markus, Julian A. Schreiber, Gunnar Goerges, Bastian Frehland, Guiscard Seebohm, Dirk Schepmann, Bernhard Wünsch
    Archiv der Pharmazie.2022;[Epub]     CrossRef
  • Ifenprodil Reduced Expression of Activated Microglia, BDNF and DREAM Proteins in the Spinal Cord Following Formalin Injection During the Early Stage of Painful Diabetic Neuropathy in Rats
    Che Aishah Nazariah Ismail, Rapeah Suppian, Che Badariah Ab Aziz, Idris Long
    Journal of Molecular Neuroscience.2021; 71(2): 379.     CrossRef
  • Ifenprodil Stereoisomers: Synthesis, Absolute Configuration, and Correlation with Biological Activity
    Elena Bechthold, Julian A. Schreiber, Kirstin Lehmkuhl, Bastian Frehland, Dirk Schepmann, Freddy A. Bernal, Constantin Daniliuc, Inés Álvarez, Cristina Val Garcia, Thomas J. Schmidt, Guiscard Seebohm, Bernhard Wünsch
    Journal of Medicinal Chemistry.2021; 64(2): 1170.     CrossRef
  • The anti-diabetic effects of betanin in streptozotocin-induced diabetic rats through modulating AMPK/SIRT1/NF-κB signaling pathway
    Nasim Abedimanesh, Somayyeh Asghari, Kosar Mohammadnejad, Zahra Daneshvar, Soudeh Rahmani, Samaneh Shokoohi, Amir Hasan Farzaneh, Seyed Hojjat Hosseini, Iraj Jafari Anarkooli, Maryam Noubarani, Sina Andalib, Mohammad Reza Eskandari, Behrooz Motlagh
    Nutrition & Metabolism.2021;[Epub]     CrossRef
  • Diabetic neuropathy and neuropathic pain: a (con)fusion of pathogenic mechanisms?
    Nigel A. Calcutt
    Pain.2020; 161(Supplement): S65.     CrossRef
  • N-Acetylcysteine causes analgesia in a mouse model of painful diabetic neuropathy
    Serena Notartomaso, Pamela Scarselli, Giada Mascio, Francesca Liberatore, Emanuela Mazzon, Santa Mammana, Agnese Gugliandolo, Giorgio Cruccu, Valeria Bruno, Ferdinando Nicoletti, Giuseppe Battaglia
    Molecular Pain.2020; 16: 174480692090429.     CrossRef
  • Effect of aerobic exercise on innate immune responses and inflammatory mediators in the spinal cord of diabetic rats
    A. Kaki, M. Nikbakht, A.H. Habibi, H.F. Moghadam
    Comparative Exercise Physiology.2020; 16(4): 293.     CrossRef
Review
Diabetic Peripheral Neuropathy in Type 2 Diabetes Mellitus in Korea
Seung-Hyun Ko, Bong-Yun Cha
Diabetes Metab J. 2012;36(1):6-12.   Published online February 17, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.1.6
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  • 30 Crossref
AbstractAbstract PDFPubReader   

Diabetic peripheral neuropathy (DPN), a common and troublesome complication in patients with type 2 diabetes mellitus (T2DM), contributes to a higher risk of diabetic foot ulcer and lower limb amputation. These situations can negatively impact the quality of life of affected individuals. Despite its high prevalence and clinical importance, most diabetes mellitus patients not only do not recognize the presence of diabetic neuropathy, but also do not report their symptoms to physicians or other health care providers. Therefore, DPN is usually under diagnosed and undertreated. For early detection and appropriate intervention for DPN, a careful history, physical with neurologic examination, and prompt treatment are needed in T2DM patients.

Citations

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  • Pramipexole protects against diabetic neuropathy: Effect on oxidative stress, TLR4/IRAK-1/TRAF-6/NF-κB and downstream inflammatory mediators
    Nada H. Eisa, Sahar A Helmy, Dalia H. El-Kashef, Mohamed El-Sherbiny, Nehal M. Elsherbiny
    International Immunopharmacology.2024; 128: 111514.     CrossRef
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    Yohannes Mekuria Negussie, Nardos Tilahun Bekele
    Scientific Reports.2024;[Epub]     CrossRef
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    Jung Hwan Park, Dong Sun Kim
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Original Articles
Association of Haplotype Combinations of Calpain-10 Gene Polymorphisms and the Metabolic Syndrome in Type 2 Diabetes.
Eun Seok Kang, Hye Joo Kim, Sung Min Myoung, Yumie Rhee, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Moonsuk Nam
Korean Diabetes J. 2005;29(5):451-459.   Published online September 1, 2005
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AbstractAbstract PDF
OBJECTIVE: Patients with metabolic syndrome are at increased risk of developing cardiovascular disease. The combinations of the haplotype created by the alleles of three single nucleotide polymorphisms (SNPs): SNP-43, SNP-19, and SNP-63 of the Calpain 10 gene (CAPN10), have been reported to be associated with the risk of type 2 diabetes (T2DM) in many populations. The aim of this study was to examine the association of the CAPN10 polymorphisms with metabolic syndrome in Korean patients with T2DM. METHODS: Overall, 382 T2DM patients were enrolled in this study. All the subjects were genotyped according to CAPN10 SNP-43, SNP-19 and SNP-63. The restriction fragment length polymorphism method was used for the three SNPs. The baseline presence of the components of metabolic syndrome was determined. RESULTS: 265 (69.4 %) patients were found to have metabolic syndrome. Patients with the 111/121 haplotype combination showed a higher risk of hypertension than the other haplotype combinations (OR=2.334, P=0.010) and also had a significantly higher risk of having metabolic syndrome (OR=1.927, P=0.042). CONCLUSION: The results of this study suggest a role of the novel 111/121 haplotype combination created by the CAPN10 SNPs -43, -19 and -63 in the susceptibility to metabolic syndrome of T2DM patients.
Analgesic Effects of DA-5018, a New Capsaicin Derivative, in Hyperalgesia of Experimental Diabetic Neuropathy.
Eun Ju Bae, Soon How Kim, Moon Ho Son, Hee Kee Kim, Myeong Soo Shin, Hyun Ji Kim, Won Bae Kim
Korean Diabetes J. 1997;21(1):91-101.   Published online January 1, 2001
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AbstractAbstract PDF
BACKGROUND
Painful peripheral neuropathy is one of the most common complications of diabetes and not responsive to conventional analgesics. Capsaicin cream has been used to treat the pain associated with diabetic neuropathy, rheumatoid arthritis, osteoarthritis and postherpetic neuralgia. But its common side effect, burning sensation, limits the use of it. DA-5018 is a newly synthesized capsaicin derivative which shows more potent systemic and topical analgesia than capsaicin in various animal models of acute and chronic pain, but has little skin irritaion. This study was designed to evaluate the effect of DA-5018 administered systemically or topically on hyperalgesia in streptozotocin-induced diabetic and galactosaemic rats. METHODS: One group of SD rats was treated with streptozotocin(60mg/kg, I.v.) and the pain thresholds were determined weekly by Randall-Selitto paw pressure test. And the other group of SD rats was maintained on 50%-galactose diet until 4~5 weeks and the pain thresholds were determined as well, Drugs were administered subcutaneously once a day for 7 days or topically to the paw for 5 hours a day for 10 days at a time when the hyperalgesia was already present. The increase of pain thresholds by drug was regarded as an indication of analgesia. RESULTS: Streptozotocin-diabetic rats displayed a reduction of pain threshold. Similarly, galactosefeeding resulted in significant reduction of pain threshold. It is concluded that hyperalgesia is a constant feature of sensory dysfunction in experimental models of diabetic and nutritional neuropathy. DA-5018(0.2, 0.5mg/kg, s.c.) produced significant antinociception with efficacy similar to that of capsaicin(10mg/kg, s.c.) in streptozotocin-induced hyperalgesia and furthermore, no tolerance developed for 7 days. And this analgesic effect was superior to desipramine(10mg/kg, s.c.). But ketoprofen(10mg/kg, s.c.) produced no analgesia. Topically, 0.3% DA-5018 cream was as effective as Zostrix-HP(capsaicin 0.075%) both in streptozotocin-diabetic and galactosefed rats while Kenofen gel(ketoprofen 3%) was ineffective to reduce pain. CONCLUSION: These results demonstrate the potent analgesic efficacy of DA-5018 in diabetic pain models and suggest that topical DA-5018 cream may relieves pain caused by diabetic neuropathy offering an alternative for patients not responsive to other treatments or unable to tolerate capsaicin.

Diabetes Metab J : Diabetes & Metabolism Journal