Skip to main content
SpringerLink
Log in

Treatment of Painful Diabetic Neuropathy

  • Chapter
  • First Online:
Diabetic Neuropathy and Clinical Practice

  • 676 Accesses

Abstract

Despite having a detailed understanding of the pathophysiology of diabetic neuropathy and considerable work on its painful part, it still remains a difficult if not impossible task to control pain in painful neuropathies in diabetes. Relief comes, often partial and almost never complete, with a heavy burden of drugs and lingering side effects. Strangely the drugs that are generally effective have little to do with the pathogenesis of the neuropathy or pain. Severe neuropathic pain often leads to depression and the drugs which are often effective in it are useful for alleviating diabetic neuropathy pain also. There are other drugs which may have to do something with pathogenesis, remain experimental or extremely difficult to administer, like C-peptide, or have been proved to be of no use at all like Aldose Reductase inhibitors despite the pathophysiological connection to their actions.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Notes

  1. 1.

    This agent has been in use extensively in India for over decade now, but the exact contributions and efficacy have not been registered in the minds of clinicians adequately clearly. Since it is a popular agent it is described under trial evidence in a little more detailed fashion to bring out clarity in this area.

  2. 2.

    In vit D correction regimens it appears to the author desirable that some study about which is more effective in correcting vit D deficiency—oral weekly doses of vit D3 against massive doses of injectable vit D2 is worthwhile. Oral vit D 3 may have to be considered as a drug reserved for those with end-stage renal disease where conversion of injected vit D 2 is not possible. But in vast majority of calcium/vit D deficiency it appears to be a legitimate question which one corrects the deficiency better and quicker. Added to that is the high cost of vit D3.

  3. 3.

    The author has seen something similar happening in areas with high content of arsenic and such other metals as in West Bengal. Oral iron replacement over months, which patients any way do not adhere to, does not change the anemia profile in any way. This frustrating experience has led the author to routinely replace iron by intravenous route. In the tribals in Tripura a peculiar microcytic anemia without much iron deficiency is seen. This is also not correctable beyond 9 g/dl, which however is an acceptable level for full functioning. Use of vit B 12 should routinely be combined with Folic acid for full hemtologic/neurological recovery.

References

  1. Boulton AJ, Vinik AI, Arezzo JC, et al. For the American Diabetes Association. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care. 2005;28:956–62.

    Article  PubMed  Google Scholar 

  2. Apfel SC, Asbury AK, Bril V, for the Ad Hoc Panel on Endpoints for Diabetic Neuropathy Trials, et al. Positive neuropathic sensory symptoms as endpoints in diabetic neuropathy trials. J Neurol Sci. 2001;189:3–5.

    Article  CAS  PubMed  Google Scholar 

  3. Attal N, Cruccu G, Baron R, Haanpaa M, Hansson P, Jensen TS, Nurmikko T. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2009 revision. Eur J Neurol. 2010;17:1113. –1e88. [PubMed: 20402746].

    Article  CAS  PubMed  Google Scholar 

  4. Dworkin RH, O'Connor AB, Audette J, Baron R, Gourlay GK, Haanpaa ML, Kent JL, Krane EJ, Lebel AA, Levy RM, Mackey SC, Mayer J, Miaskowski C, Raja SN, Rice AS, Schmader KE, Stacey B, Stanos S, Treede RD, Turk DC, Walco GA, Wells CD. Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clin Proc. 2010;85:S3–S14. [PubMed: 20194146].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Moulin DE, Clark AJ, Gilron I, Ware MA, Watson CP, Sessle BJ, Coderre T, Morley-Forster PK, Stinson J, Boulanger A, Peng P, Finley GA, Taenzer P, Squire P, Dion D, Cholkan A, Gilani A, Gordon A, Henry J, Jovey R, Lynch M, Mailis-Gagnon A, Panju A, Rollman GB, Velly A. Pharmacological management of chronic neuropathic pain - consensus statement and guidelines from the Canadian Pain Society. Pain Res Manag. 2007;12:13–21. [PubMed: 17372630].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Acevedo JC, Amaya A, Casasola OL, Chinchilla N, De GM, Florez S, Genis MA, Gomez-Barrios JV, Hernandez JJ, Ibarra E, Moreno C, Orrillo E, Pasternak D, Romero S, Vallejo M, Velasco M, Villalobos A. Guidelines for the diagnosis and management of neuropathic pain: consensus of a group of Latin American experts. J Pain Palliat Care Pharmacother. 2009;23:261–81. [PubMed: 19670022].

    Article  PubMed  Google Scholar 

  7. Bohlega S, Alsaadi T, Amir A, Hosny H, Karawagh AM, Moulin D, Riachi N, Salti A, Shelbaya S. Guidelines for the pharmacological treatment of peripheral neuropathic pain: expert panel recommendations for the middle east region. J Int Med Res. 2010;38:295–317. [PubMed: 20515552].

    Article  CAS  PubMed  Google Scholar 

  8. Attal N, Cruccu G, Haanpaa M, Hansson P, Jensen TS, Nurmikko T, Sampaio C, Sindrup S, Wiffen P. EFNS guidelines on pharmacological treatment of neuropathic pain. Eur J Neurol. 2006;13:1153–69. [PubMed: 17038030].

    Article  CAS  PubMed  Google Scholar 

  9. Dooley DJ, Mieske CA, Borosky SA. Inhibition of K(+)-evoked glutamate release from rat neocortical and hippocampal slices by gabapentin. Neurosci Lett. 2000;280:107–10.

    Article  CAS  PubMed  Google Scholar 

  10. Maneuf YP, McKnight AT. Block by gabapentin of the facilitation of glutamate release from rat trigeminal nucleus following activation of protein kinase C or adenylyl cyclase. Br J Pharmacol. 2001;134:237–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Dooley DJ, Donovan CM, Pugsley TA. Stimulus-dependent modulation of [3H]-norepinephrine release from rat neocortical slices by gabapentin and pregabalin. J Pharmacol Exp Ther. 2000;295:1086–93.

    CAS  PubMed  Google Scholar 

  12. Field MJ, Oles RJ, Singh L. Pregabalin may represent a novel class of anxiolytic agents with a broad spectrum of activity. Br J Pharmacol. 2001;132:1–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Basbaum AI, Fields HL. Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry. Annu Rev Neurosci. 1984;7:309–38.

    Article  CAS  PubMed  Google Scholar 

  14. Fehrenbacher JC, Taylor CP, Vasko MR. Pregabalin and gabapentin reduce release of substance P and CGRP from rat spinal tissues only after inflammation or activation of protein kinase C. Pain. 2003;105:133–41.

    Article  CAS  PubMed  Google Scholar 

  15. Dooley DJ, Donovan CM, Meder WP, et al. Preferential action of gabapentin and pregabalin at P/Q-type voltage-sensitive calcium channels: inhibition of K-evoked [3H]-norepinephrine release from rat neocortical slices. Synapse. 2002;45:171–90.

    Article  CAS  PubMed  Google Scholar 

  16. Busch J, Strand JA, Posvar EL, et al. Pregabalin single-dose pharmacokinetics and safety/tolerance in healthy subjects after oral administration of pregabalin solution or capsule doses. Epilepsia. 1998;39(suppl 6):58. Abstract.

    Google Scholar 

  17. Jones DL, Sorkin LS. Systemic gabapentin and S(+)-3-isobutyl-gammaaminobutyric acid block secondary hyperalgesia. Brain Res. 1998;81:93–9.

    Article  Google Scholar 

  18. Gilron I, Bailey JM, Tu D, Holden RR, Weaver DF, Houlden RL. Morphine, gabapentin, or their combination for neuropathic pain. N Engl J Med. 2005;352:1324–34.

    Article  CAS  PubMed  Google Scholar 

  19. Wong M-c, Chung JWY, Wong TKS. Effects of treatments for symptoms of painful diabetic neuropathy: systematic review. BMJ. 2007;335:87.; originally published online 11 Jun 2007. https://doi.org/10.1136/bmj.39213.565972.AE.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Clark FM, Proudfit HK. The projections of noradrenergic neurons in the A5 catecholamine cell group to the spinal cord in the rat: anatomical evidence that A5 neurons modulate nociception. Brain Res. 1993;616:200–10.

    Article  CAS  PubMed  Google Scholar 

  21. Coderre TJ, Katz J. Peripheral and central hyperexcitability: differential signs and symptoms in persistent pain. Behav Brain Sci. 1997;20:404–19.

    Article  CAS  PubMed  Google Scholar 

  22. Rowbotham MC, Goli V, Kunz NR, et al. Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study. Pain. 2004;110:697–706.

    Article  CAS  PubMed  Google Scholar 

  23. Davis JL, Smith RL. Painful peripheral diabetic neuropathy treated with venlafaxine HCL extended release capsules. Diabetes Care. 1999;22:1909–10.

    Article  CAS  PubMed  Google Scholar 

  24. Lithner F. Venlafaxine in treatment of severe painful peripheral diabetic neuropathy. Diabetes Care. 2000;23:1710–1.

    Article  CAS  PubMed  Google Scholar 

  25. Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG, et al. Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology. 2001;25:871–80.

    Article  CAS  PubMed  Google Scholar 

  26. Gimbel JS, Richards P, Portenoy RK. Controlled release oxycodone for pain in diabetic neuropathy, A randomized controlled trial. Neurology. 2003;60:927.

    Article  CAS  PubMed  Google Scholar 

  27. Kroemer HK, Eichelbaum M. “It's the genes, stupid”. Molecular bases and clinical consequences of genetic cytochrome P450 2D6 polymorphism. Life Sci. 1995;56:2285–98. [PubMed: 7791516].

    Article  CAS  PubMed  Google Scholar 

  28. Binder W, Walker JS. Effect of the peripherally selective kappa-opioid agonist, asimadoline, on adjuvant arthritis. Br J Pharmacol. 1998;124:647–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Finnerup NB, Attal N. Pharmacotherapy of neuropathic pain: time to rewrite the rulebook? Pain Manag. 2016;6:1–3. [PubMed: 26678278].

    Article  PubMed  Google Scholar 

  30. Finnerup NB, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14:162–73. [PubMed: 25575710].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Tesfaye S, et al. Duloxetine and pregabalin: high-dose monotherapy or their combination? The “COMBO-DN study” — a multinational, randomized, double-blind, parallel-group study in patients with diabetic peripheral neuropathic pain. Pain. 2013;154:2616–25. [PubMed: 23732189].

    Article  CAS  PubMed  Google Scholar 

  32. Vinik AI, et al. Capsaicin 8% patch repeat treatment plus standard of care (SOC) versus SOC alone in painful diabetic peripheral neuropathy: a randomised, 52-week, open-label, safety study. BMC Neurol. 2016;16:251. [PubMed: 27919222].

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Cruccu G, et al. EFNS guidelines on neurostimulation therapy for neuropathic pain. Eur J Neurol. 2007;14:952–70. [PubMed: 17718686].

    Article  CAS  PubMed  Google Scholar 

  34. Dworkin RH, et al. Interventional management of neuropathic pain: NeuPSIG recommendations. Pain. 2013;154:2249–61. [PubMed: 23748119].

    Article  PubMed  PubMed Central  Google Scholar 

  35. Ziegler D, Ametov A, Barinov A, Dyck PJ, Gurieva I, Low PA, Munzel U, Yakhno N, Raz T, Novosadova M, Maus J, Samigullin R. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy TheSYDNEY2 trial. Diabetes Care. 2006;29:2365–70.

    Article  CAS  PubMed  Google Scholar 

  36. Agathos E, Tentolouris A, Eleftheriadou I, Katsaouni P, Nemtzas I, Petrou A, Papanikolaou C, Tentolouris N. Effect of a-lipoic acid on symptoms and quality of life in patients with painful diabetic neuropath. J Int Med Res. 2018;46(5):1779–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Vinik AI, Bril V, Kempler P, Litchy WJ, Tesfaye S, Price KL, Bastyr EJ III. Treatment of symptomatic diabetic peripheral neuropathy with the protein kinase C beta-inhibitor ruboxistaurin mesylate during 1year, randomized, placebo-controlled, Double-Blind Clinical Trial. Clin Ther., Express Track online publication. 2005; https://doi.org/10.1016/j.clinthera.2005.08.001.

    Article  CAS  PubMed  Google Scholar 

  38. Cameron NE, Cotter MA. Metabolic and vascular factors in the patho-genesis of diabetic neuropathy. Diabetes. 1997;46(Suppl 2):S31–7.

    Article  CAS  PubMed  Google Scholar 

  39. Ways DK, Sheetz MJ. The rote of protein kinase C in the development of the complications of diabetes. Vitam Horm. 2000;60:149–93.

    Article  CAS  PubMed  Google Scholar 

  40. Ozaki H, Yasuda K, Kim YS, et al. Possible role of the protein kinase C/CPI-17 pathway in the augmented contraction of human myometrium after gestation. Br J Pharmacol. 2003;140:1303–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Vinik A, Tesfaye S, Zhang D, Bastyr E, for the MBBQ Study Group. LY333531 treatment improves diabetic peripheral neuropathy (DPN) with symptoms. Diabetes. 2002;51(Suppl 2):A79.

    Google Scholar 

  42. Bril V, Vinik AI, Litchy WJ, for the MBBQ Study Group, et al. Detectable sural nerve action potential (SNAP) identifies patients with early diabetic peripheral neuropathy (DPN). Diabetes. 2002;51(Suppl 2):A197.

    Google Scholar 

  43. Balbi ME, Tonin FS, Mendes AM, Borba HH, Wiens A. Antioxidant effects of vitamins in type 2 diabetes: a meta-analysis of randomized controlled trials. Diabetol Metab Syndr. 2018;10:18. Published online 2018 Mar 14. https://doi.org/10.1186/s13098-018-0318-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Tutuncu NB, Bayraktar M, Varli K. Reversal of defective nerve conduction with vitamin E supplementation in type 2 diabetes – a preliminary study. Diabetes Care. 1998;21:1915–8.

    Article  CAS  PubMed  Google Scholar 

  45. Finnerup NB, Otto M, Mcquay HJ, Jensen TS, Sindrup SH. Algorithm for neuropathic pain treatment: an evidence based proposal. Pain. 2005;118:289–305.

    Article  CAS  PubMed  Google Scholar 

  46. Reichstein L, Labrenz S, Ziegler D, Martin S. Effective treatment of symptomatic diabetic polyneuropathy by high-frequency external muscle stimulation. Diabetologia. 2005;48:824–8. https://doi.org/10.1007/s00125-005-1728-0.

    Article  CAS  PubMed  Google Scholar 

  47. Bevilacqua M, Barrella M, Toscano R et al (2004) Disturbances of vasomotion in diabetic (type 2) neuropathy: increase of vascular endothelial growth factor, elicitation of sympathetic efflux and synchronization of vascular flow (vasomotion)during frequency modulated neural stimulation (FREMS). 86th Annual Meeting of the Endocrine Society, p 321, P 2–61 (abstract).

    Google Scholar 

  48. Bosi E, Conti M, Vermigli C, Cazzetta G, Peretti E, Cordoni MC, Galimberti G, Scionti L. Effectiveness of frequency-modulated electromagnetic neural stimulation in the treatment of painful diabetic neuropathy. Diabetologia. 2005;48:817–23. https://doi.org/10.1007/s00125-005-1734-2.

    Article  CAS  PubMed  Google Scholar 

  49. Clifft JK, Kasser RJ, Newton TS, Bush AJ. The effect of monochromatic infrared energy on sensation in patients with diabetic peripheral neuropathy a double-blind, placebo-controlled study. Diabetes Care. 2005;28:2896–900.

    Article  PubMed  Google Scholar 

  50. Attal N, et al. Safety and efficacy of repeated injections of botulinum toxin a in peripheral neuropathic pain (BOTNEP): a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2016;15:555–65.

    Article  CAS  PubMed  Google Scholar 

  51. Shackleton T, et al. The efficacy of botulinum toxin for the treatment of trigeminal and postherpetic neuralgia: a systematic review with meta-analyses. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016;122:61–71. [PubMed: 27260275].

    Article  PubMed  Google Scholar 

  52. Lakhan SE, Velasco DN, Tepper D. Botulinum toxin-a for painful diabetic neuropathy: a metaanalysis. Pain Med. 2015;16:1773–80. [PubMed: 25800040].

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Independent Health Researcher, Pune, Maharashtra, India

    Sanjeev Kelkar

Authors
  1. Sanjeev Kelkar
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kelkar, S. (2020). Treatment of Painful Diabetic Neuropathy. In: Diabetic Neuropathy and Clinical Practice. Springer, Singapore. https://doi.org/10.1007/978-981-15-2417-2_12

Download citation

  • DOI: https://doi.org/10.1007/978-981-15-2417-2_12

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-15-2416-5

  • Online ISBN: 978-981-15-2417-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation