Skip to main content
The Egyptian Journal of Internal Medicine
Download PDF
  • Original article
  • Open access
  • Published:

Acetylcholine iontophoresis in diabetic patients with and without peripheral neuropathy: a potential therapeutic tool

The Egyptian Journal of Internal Medicine volume 30, pages 140–144 (2018)Cite this article

Abstract

Background

Iontophoresis had been widely used as a therapeutic option in the field of dermatology and physiotherapy. In vascular medicine, vasodilating response to acetylcholine (ACh) iontophoresis had been also previously studied in the evaluation of endothelial dysfunction in diabetes mellitus and its microvascular complications but less was published about its therapeutic implementations. The current study aimed at investigating the therapeutic role of ACh iontophoresis in the improvement of endothelial dysfunction seen in diabetic patients with and without peripheral neuropathy (PN).

Patients and methods

Forty patients with type 2 diabetes mellitus, 20 with and 20 without PN, were subjected to a therapeutic program of ACh iontophoresis three times a week for 2 successive weeks ‘long-term iontophoresis’. Percentage change in perfusion was measured in the two groups using laser Doppler flowmetry. Readings were taken pretreatment and post-treatment on three occasions: at baseline temperature, after local warming to 35°C, and at maximal flow after exposure to ACh iontophoresis ‘short-term iontophoresis’.

Results

Perfusion significantly improved after 2 weeks of therapy in the two groups with percentage change improvement of 180.65 vs. 131.50% in the baseline, 219.45 vs. 149.40% after local warming to 35°C and 269.60 vs. 236.95% after short-term ACh iontophoresis in patients without and those with PN, respectively, with P values of 0.0004, 0.0005, and 0.049, respectively.

Conclusion

ACh iontophoresis may be an optional treatment procedure for improving cutaneous perfusion in diabetics for further randomized control studies.

References

  1. Korula M. Iontophoretic delivery of drugs. Indian Anaesth Forum 2004; 94:1484–1488.

    Google Scholar 

  2. Eisenach JH, Atkinson JL, Fealey RD. Hyperhidrosis: evolving therapies for a well-established phenomenon. Mayo Clin Proc 2005; 80:657–666.

    Article  Google Scholar 

  3. Goyal M, Kumar A, Mahajan N, Moitra M. Treatment of plantar fasciitis by taping vs. iontophoresis: a randomized clinical trial. J Exercise Sci Physiother 2013; 9:34–39.

    Google Scholar 

  4. Zecuity. NuPathe’s Zecuity approved by the FDA for the acute treatment of migraine. Available at: http://ir.nupathe.com/press-releases. (Accessed 25 April 2013).

  5. Zhao M, Song B, Pu J, Wada T, Reid B, Tai G, et al. Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN. Nature 2006; 442:457–460.

    Article  CAS  Google Scholar 

  6. Murray AK, Moore TL, King TA, Herrick AL. Vasodilator iontophoresis: a possible new therapy for digital ischaemia in systemic sclerosis?.. Rheumatology 2008; 47:76–79.

    Article  CAS  Google Scholar 

  7. Cordovil I, Huguenin G, Rosa G, Bello A, Köhler O, De Moraes R, et al. Evaluation of systemic microvascular endothelial function using laser speckle contrast imaging. Microvasc Res 2012; 83:376–379.

    Article  Google Scholar 

  8. Morris SJ, Shore AC. Skin blood flow responses to the iontophoresis of acetylcholine and sodium nitroprusside in man: possible mechanisms. J Physiol. 1996; 496:531–542.

    Article  CAS  Google Scholar 

  9. Puissant C, Abraham P, Durand S, Humeau-Heurtier A, Faure S, Rousseau P, et al. Endothelial function: role, assessment and limits. J Mal Vasc 2014; 39:47–56.

    Article  CAS  Google Scholar 

  10. Sauvet F, Mahé G, Chennaoui M, Langrume C, Vasseur M, Abraham P, et al. Acetylcholine chloride as a potential source of variability in the study of cutaneous vascular function in man. Microvasc Res 2011; 82:190–197.

    Article  CAS  Google Scholar 

  11. Ruderman A, Williamson N, Brownlee M. Glucose and diabetic vascular disease. FASEB J 1992; 6:2905–2914.

    Article  CAS  Google Scholar 

  12. Brownlee M, Cerami A, Vlassara H. Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med 1988; 318:1315–1321.

    Article  CAS  Google Scholar 

  13. Asad A, Hameed MA, Khan UA, Ahmed N, Butt MU. Reliability of the neurological scores for assessment of sensorimotor neuropathy in type 2 diabetics. J Pak Med Assoc 2010; 60:166–170.

    PubMed  Google Scholar 

  14. Tanenberg RJ. Diabetic peripheral neuropathy: painful or painless. Hosp Physician 2009; 45:1–8.

    Google Scholar 

  15. Elashmaoui A, Nashaat M, Abdelghany H. Endothelial dysfunction and microangiopathic changes in first degree relatives of patients with type 2 diabetes assessed by iontophoresis. European Society For Microcirculation: 23rd Conference, Lisbon, Portugal, Microcirculation and Vascular Biology: a basis for research and a reason for life. J Vasc Res 2004; 8:319–324.

    Google Scholar 

  16. Brooks BA, Melennan SV, Twigg SM, Yu DK. Detection and characterization of microcirculatory abnormalities in the skin of diabetic patients with microvascular complications. Diab Vasc Dis Res 2008; 5:30–35.

    Article  Google Scholar 

  17. Singh PK, Kumar S, Easwari TS, Shukla VK, Chaudhary R, Verma P. Iontophoretic delivery of drugs: maximizing treatment effectiveness. Int J Pharm Sci Letters 2011; 1:28–33.

    Google Scholar 

  18. Kellogg DL Jr, Crandall CG, Liu Y, Charkoudian N, Johnson JM. Nitric oxide and cutaneous active vasodilation during heat stress in humans. J Appl Physiol 1998; 85:824–829.

    Article  CAS  Google Scholar 

  19. Kellogg DL Jr, Johnson JM, Kosiba WA. Selective abolition of adrenergic vasoconstrictor responses in skin by local iontophoresis of bretylium. Am J Physiol 1989; 257:1599–1606.

    Google Scholar 

  20. Kelly J, Cassella JP, Ashford RL, Thomkin GH. An iontophoretic study of the endothelial response in the diabetic foot with symmetrical sensory neuropathy. Foot 2001; 11:144–150.

    Article  Google Scholar 

  21. Hamdy O, Abou-Elenin K, LoGerfo FW, Horton ES, Veves A. Contribution of nerve axon reflex related vasodilation to the total skin vasodilation in diabetic patients with and without neuropathy. Diabetes Care 2001; 24:344–349.

    Article  CAS  Google Scholar 

  22. Zimny S, Dessel F, Ehren M, Pfohl M, Schatz H. Early detection of microcirculatory impairment in diabetic patients with foot at risk. Diabetes Care 2001; 24:1810–1814.

    Article  CAS  Google Scholar 

  23. Arora S, Pomposelli F, Logerfo FW, Veves A. Cutaneous microcirculation in the neuropathic diabetic foot improves significantly but not completely after successful lower extremity revascularization. J Vasc Surg 2002; 35:501–505.

    Article  Google Scholar 

  24. Quattrini C, Harris ND, Malik RA, Tesfaye S. Impaired skin microvascular reactivity in painful diabetic neuropathy. Diabetes Care 2007; 30:655–659.

    Article  Google Scholar 

  25. Christen S, Delachaux A, Dischl B, Golay S, Liaudet L, Feihl F, et al. Dose dependent vasodilatory effects of Acetylcholine and local warming on skin microcirculation. J Cardiovasc Pharmacol 2004; 44:659–664.

    Article  CAS  Google Scholar 

  26. Beer S, Feihl F, Ruiz J, Juhan-Vague L, Aillaud MF, Wetzel SG, et al. Comparison of skin microvascular reactivity with hemostatic markers of endothelial dysfunction and damage in type 2 diabetes. Vascu Health Risk Manag 2008; 4:1449–1458.

    Article  CAS  Google Scholar 

  27. Kalia YN, Naik A, Garrison J, Guy RH. Iontophoretic drug delivery. Adv Drug Deliv Rev 2004; 56:619–658.

    Article  CAS  Google Scholar 

  28. Tesselaar E, Sjoberg F. Transdermal iontophoresis as an in-vivo technique for studying microvascular physiology. Microvasc Res 2011; 81:88–96.

    Article  CAS  Google Scholar 

  29. Ramsay JE, Ferrell WR, Greer IA, Sattar N. Factors critical to iontophoretic assessment of vascular reactivity: implications for clinical studies of endothelial function. J Cardiovasc Pharmacol 2002; 39:9–17.

    Article  CAS  Google Scholar 

  30. Walch L, Norel X, Leconte B, Gascard JP, Brink C. Cholinergic control of human and animal pulmonary vascular tone. Therapie 1999; 54: 99–102.

    CAS  PubMed  Google Scholar 

  31. Thomas I, Brown J, Vafai J, Schwartz RA. Palmoplantar hyperhydrosis: a therapeutic challenge. Am Fam Physician 2004; 69:1117–1121.

    PubMed  Google Scholar 

  32. Durand S, Tartas M, Bouye P, Koitka A, Saumet JL, Abraham P. Prostaglandins participate in the late phase of the vascular response to acetylcholine iontophoresis in humans. J Physiol 2004; 561:811–819.

    Article  CAS  Google Scholar 

  33. Ward JD. Upright posture and the microvasculature in human diabetic neuropathy: a hypothesis. Diabetes 1997; 46:S94–S97.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Physical Therapy, Faculty of Physical Therapy, Cairo University, Cairo, Egypt

    Ibrahim Ismail Abu Zaid

  2. Department of Internal Medicine, Cairo University, Cairo, Egypt

    Mohamed Ahmed Hussein MD, MSc & Alaa A. Hamid

  3. Physical Therapy for Cardiovascular/ Respiratory disorders and Geriatrics, Faculty of Physical Therapy, Cairo University, Cairo, Egypt

    Gihan Samir Mousa & Nagwa Mohamed Badr

  4. Physical Therapy, Critical Care Department, Cairo University Hospitals, Cairo, Egypt

    Amany Raafat Mohamed

Authors
  1. Ibrahim Ismail Abu Zaid
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohamed Ahmed Hussein MD, MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gihan Samir Mousa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Amany Raafat Mohamed
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nagwa Mohamed Badr
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alaa A. Hamid
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mohamed Ahmed Hussein MD, MSc.

Additional information

This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zaid, I.I.A., Hussein, M.A., Mousa, G.S. et al. Acetylcholine iontophoresis in diabetic patients with and without peripheral neuropathy: a potential therapeutic tool. Egypt J Intern Med 30, 140–144 (2018). https://doi.org/10.4103/ejim.ejim_51_17

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.4103/ejim.ejim_51_17

Keywords