Skip to main content

Advertisement

SpringerLink
Log in

Modulation of neuropathic pain in experimental diabetes mellitus

  • Original Paper
  • Published:
Journal of Physiology and Biochemistry Aims and scope Submit manuscript

Abstract

The main objective of the current article is to investigate the diabetic polyneuropathy which represents a major preoccupation within the context of high incidence of diabetes mellitus (DM) and its complications. Moreover, neuropathy may develop despite intensive hyperglycaemic control. The effect of Zn and black grape seed polyphenols (BGSP) in streptozotocin diabetic rats was studied. Zn and BGSP were administered by gavage, daily, for 16 weeks to Wistar rats that have been rendered diabetic by a single i.v. injection of streptozotocin (55 mg/kg body weight). Dysalgesia was investigated under the conditions of nociceptive stimulation through the following tests: the thermoalgesic mechanism through the tail-flick test, the hot plate test and the plantar test, and the mechanoalgesic mechanism through the algesimetric test. Thermal hyperalgesia detected in the diabetic group is significantly reduced (p < 0.001) through the administration of polyphenols, or even better, of Zn. Diabetes-associated mechanical hyperalgesia decreased significantly (p < 0.001) probably through the inhibition of the NMDA receptors. Administration of Zn or BGSP to the diabetic group improves glycosylated haemoglobin (HbA1c) values but does not bring them to normal. The present data suggest a favourable effect of Zn and BGSP in inhibiting diabetic complications by several mechanisms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ahmed N (2005) Advanced glycation endproducts—role in pathology of diabetic complications. Diabetes Res Clin Pract 67(1):3–21

    Article  CAS  PubMed  Google Scholar 

  2. Ahmed N, Thornalley PJ (2007) Advanced glycation endproducts: what is their relevance to diabetic complications? Diabetes Obes Metab 9(3):233–245

    Article  CAS  PubMed  Google Scholar 

  3. Ametov A, Barinov A, Dyck PJ, Hermann R (2003) The sensory symptoms of diabetic polyneuropathy are improved with lipoic acid. The SYDNEY trial. Diabetes Care 26:770–776

    Article  CAS  PubMed  Google Scholar 

  4. Andreassen CS, Jakobsen J, Andersen H (2006) Muscle weakness, a progressive late complication in diabetic distal symmetric polyneuropathy. Diabetes 55:806–812

    Article  CAS  PubMed  Google Scholar 

  5. Aziz MTA, Ibrashy INE, Mikhailidis DP et al (2013) Signalling mechanisms of a water soluble curcumin derivative in experimental type 1 diabetes with cardiomyopathy. Diabetol Metab Syndr 5:13. doi:10.1186/1758-5996-5-13

    Article  PubMed Central  PubMed  Google Scholar 

  6. Balasundram N, Sundram K, Saman S (2006) Phenolic compounds in plants and agro-industrial by-products: antioxidant activity, occurrence and potential uses. Food Chem 99:191–203

    Article  CAS  Google Scholar 

  7. Boulton AJ, Malik RA, Arezzo JC, Sosenko JM (2004) Diabetic somatic neuropathies. Diabetes Care 27:1458–1486

    Article  PubMed  Google Scholar 

  8. Boulton AJ, Vinik A, Arezzo J, Bril V, Feldman E, Freeman R, Malik R, Maser R, Sosenko J, Ziegler D (2005) Diabetic neuropathies. A statement by the American Diabetes Association. Diabetes Care 28:956–962

    Article  PubMed  Google Scholar 

  9. Cheynier V (2005) Polyphenols in foods are more complex than often thought. Am J Clin Nutr 81:223S–229S

    CAS  PubMed  Google Scholar 

  10. Feldman EL (2003) Oxidative stress and diabetic neuropathy: a new understanding of an old problem. J Clin Invest 111(4):431–433

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Freeman R (2005) Autonomic peripheral neuropathy. Lancet 365:1259–1270

    Article  CAS  PubMed  Google Scholar 

  12. Gilgun-Sherki Y, Rosenbaum Z, Melamed E, Offen D (2002) Antioxidant therapy in acute central nervous system injury: current state. Pharmacol 54:271–284

    CAS  Google Scholar 

  13. Gooch C, Podwall D (2004) The diabetic neuropathies. Neurologist 10(6):311–322

    Article  PubMed  Google Scholar 

  14. Guy RJC (2002) Evaluation of thermal and vibration sensation in diabetic neuropathy. Diabetologia 28:131–137

    Google Scholar 

  15. Haupt E, Ledermann H, Kopcke W (2005) Benfotiamine in the treatment of diabetic polyneuropathy—a three-week randomized, controlled pilot study (BEDIP study). Int J Clin Pharmacol Ther 43(2):71–77

    Article  CAS  PubMed  Google Scholar 

  16. Jensen TS, Backonja MM, Hernández Jiménez S, Tesfaye S, Valensi P, Ziegler D (2006) New perspectives on the management of diabetic peripheral neuropathic pain. Diab Vasc Dis Res 3:108–119

    Article  PubMed  Google Scholar 

  17. Kahn AH, Pessin JE (2002) Insulin regulation of glucose uptake: a complex interplay of intracellular signalling pathways. Diabetologia 45:1475–1483

    Article  Google Scholar 

  18. Kaneto H, Kajimoto Y, Miyagawa J, Matruoka T, Fujitani Y, Umayahara Y, Hanafusa T, Matsuzawa Y, Yamasaki Y, Hori M (1999) Beneficial effects of antioxidants in diabetes. Possible protection of pancreatic beta-cells against glucose toxicity. Diabetes 48:2398–2406

    Article  CAS  PubMed  Google Scholar 

  19. King H, Aubert R, Herman W (1998) Global burden of diabetes, 1995-2025. Prevalence, numerical estimates and projections. Diabetes Care 21:1414–1431

    Article  CAS  PubMed  Google Scholar 

  20. Landrault N, Poucheret P, Azay J et al (2003) Effect of the polyphenols-enriched Chardonnay white wine in diabetic rats. J Agric Food Chem 51:311–318

    Article  CAS  PubMed  Google Scholar 

  21. Leikert JF, Rathel TR, Wohlfart P et al (2002) Red wine polyphenols enhance endothelial nitric oxide synthase expression and subsequent nitric oxide release from endothelial cells. Circulation 106:1614–1617

    Article  CAS  PubMed  Google Scholar 

  22. Low PA, Benrud-Larson LM, Sletten DM, Tonette L (2004) Autonomic symptoms and diabetic neuropathy. A population-based study. Diabetes Care 27:2942–2947

    Article  PubMed  Google Scholar 

  23. Misawa S, Kuwabara S, Ogawara K, Kitano Y, Yagui K, Hattori T (2004) Hyperglycemia alters refractory periods in human diabetic neuropathy. Clin Neurophysiol 115(11):2525–2529

    Article  CAS  PubMed  Google Scholar 

  24. Morley GK, Mooradian AD, Levine AS et al (1984) Mechanism of pain in diabetic peripheral neuropathy. Effect of glucose on pain perception in humans. Am J Med 77(1):79–82

    Article  CAS  PubMed  Google Scholar 

  25. Oberly LW (1988) Free radicals and diabetes. Free Radic Biol Med 5:113–124

    Article  Google Scholar 

  26. Obrosova IG, Julius UA (2005) Role for poly(ADP-ribose) polymerase activation in diabetic nephropathy, neuropathy and retinopathy. Curr Vasc Pharmacol 3:267–283

    Article  CAS  PubMed  Google Scholar 

  27. Prior RL (2003) Fruits and vegetables in the prevention of cellular oxidative damage. Am J Clin Nutr 78:570S–578S

    CAS  PubMed  Google Scholar 

  28. Rajbhandari SM, Piya MK (2005) A brief review on the pathogenesis of human diabetic neuropathy: observations and postulations. Int J Diab Metab 13:135–140

    Google Scholar 

  29. Scalbert A, Manach C, Morand C, Remesy C, Jimenez L (2005) Dietary polyphenols and the prevention of diseases. Crit Rev Food Sci Nutr 45:287–306

    Article  CAS  PubMed  Google Scholar 

  30. Simonyi A, Wang Q, Miller RL et al (2005) Polyphenols in cerebral ischemia. Molec Neurobiol 31:135–147

    Article  CAS  Google Scholar 

  31. Stracke H, Hammes HP, Werkmann D et al (2001) Efficacy of benfotiamine versus thiamine on function and glycation products of peripheral nerves in diabetic rats. Exp Clin Endocrinol Diabetes 109(6):330–336

    Article  CAS  PubMed  Google Scholar 

  32. Sun AY, Chen YM (2002) Oxidative stress and neurodegenerative disorders. J Biomed Sci 5:401–414

    Article  Google Scholar 

  33. Sundkvist G, Dahlin LB, Nilsson H et al (2000) Sorbitol and myo-inositol levels and morphology of sural nerve in relation to peripheral nerve function and clinical neuropathy in men with diabetic, impaired, and normal glucose tolerance. Diabet Med 17:259–268

    Article  CAS  PubMed  Google Scholar 

  34. Vinik AI (2004) Advances in diabetes for the millenium: new treatments for diabetic neuropathies. Med Gen Med 6(2):13–17

    Google Scholar 

  35. Vlassara H, Palace MR (2002) Diabetes and advanced glycation end products. J Intern Med 251:87–101

    Article  CAS  PubMed  Google Scholar 

  36. Wang X, Wang B, Fan Z, Shi X, Ke ZJ, Luo J (2007) Thiamine deficiency induces endoplasmic reticulum stress in neurons. Neuroscience 144(3):1.045– 1.056

    Article  Google Scholar 

  37. Weis J, Dimpfel W, Schröder JM (2005) Nerve conduction changes and fine structural alterations of extra-and intrafusal muscle and nerve fibers in streptozotocin diabetic rats. Muscle Nerve 48:175–184

    Google Scholar 

  38. Wu S, Ren J (2006) Benfotiamine alleviates diabetes-induced cerebral oxidative damage independent of advanced glycation end-product, tissue factor and TNF-alpha. Neurosci Lett 394(2):158–162

    Article  CAS  PubMed  Google Scholar 

  39. Yao LH, Jiang YM, Shi J, Tomas-Barberan FA, Datta N, Singanusong R, Chen SS (2004) Flavonoids in food and their health benefits. Plant Foods Hum Nutr 59:113–122

    Article  CAS  PubMed  Google Scholar 

  40. Yeh GY, Eisenberg DM, Kaptchuk TJ, Phillips RS (2003) Systematic review of herbs and dietary supplements for glycemic control in diabetes. Diabetes Care 26:1277–1294

    Article  CAS  PubMed  Google Scholar 

  41. Ziegler D, Sohr C, Nourooz-Zadeh J (2004) Oxidative stress and antioxidant defense in relation to the severity of diabetic polyneuropathy and cardiovascular autonomic neuropathy. Diabetes Care 27:2178–2183

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cellular and Molecular Biology, University of Medicine and Pharmacy “Grigore T. Popa”, Universitatii St.16, Iasi, 700115, Romania

    Laurentiu Bădescu

  2. Department of Pathophysiology, University of Medicine and Pharmacy “Grigore T. Popa”, Universitatii St.16, Iasi, 700115, Romania

    Oana Bădulescu, Manuela Ciocoiu & Magda Bădescu

Authors
  1. Laurentiu Bădescu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Oana Bădulescu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Manuela Ciocoiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Magda Bădescu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Manuela Ciocoiu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bădescu, L., Bădulescu, O., Ciocoiu, M. et al. Modulation of neuropathic pain in experimental diabetes mellitus. J Physiol Biochem 70, 355–361 (2014). https://doi.org/10.1007/s13105-013-0309-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13105-013-0309-9

Keywords

Search

Navigation