The effects of botulinum toxin type A injection on pain symptoms, quality of life, and sleep quality of patients with diabetic neuropathy: A randomized double-blind clinical trial

  • Hossein Salehi Department of Plastic and Reconstructive Surgery, School of Medicine, Rafsanjan University of Medical Sciences, Iran Clinical Research Development Center, Ali Ibn Abi Talib Hospital, Rafsanjan University of Medical Sciences, Iran
  • Moein Moussaei School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  • Zahra Kamiab Department of Social Medicine, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran Clinical Research Development Unit, Ali Ibn Abi Talib Hospital, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  • Alireza Vakilian Department of Neurology, School of Medicine, University of Medical Sciences, Rafsanjan, Iran Non-Communicable Diseases Research Center, Ali Ibn Abi Talib Hospital, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
Keywords: Diabetic Neuropathies, Botulinum A Toxin, Quality of Life, Sleep


Background: Neuropathic pain is one of the most common problems in patients with diabetes mellitus (DM). In this study, the effect of botulinum toxin type A (BTX-A) on neuropathic pain, quality of sleep, and quality of life of diabetic patients with sensorimotor polyneuropathy was studied.

Methods: This randomized placebo-controlled trial study was carried out in a double-blind (patient-researcher) method. The study was performed on 32 patients with type 2 DM. Neuropathy was confirmed by Douleur Neuropathique 4 (DN4) Questionnaire and nerve conduction study (NCS). The patients were randomly assigned to two intervention and control groups based on the random numbers table. After selecting the subjects, we used 36-Item Short Form Health Survey (SF-36), Neuropathic Pain Scale (NPS), Visual Analogue Scale (VAS), and Pittsburgh Sleep Quality Index (PSQI) questionnaires before and after 3 months of 100 units BTX-A injection (as intervention group) or same amount of chloride sodium (as control group) to the subjects' feet. The data were analyzed by SPSS software using independent two-sample t-test, chi-square test, and one-way repeated measures analysis of variance (ANOVA).

Results: 12 male and 20 female patients participated in this study. There was a significant difference in the mean VAS, PSQI, physical dimension of the SF-36, and some NPS indices over time (12 weeks) (P < 0.001).

Conclusion: The results of this study showed that BTX-A reduced neuropathic pain and improved the quality of life and sleep in people with diabetic neuropathy.


1. Boulton AJ. Diabetic neuropathy: Classification, measurement and treatment. Curr Opin Endocrinol Diabetes Obes 2007; 14(2): 141-5.
2. Baron R. Mechanisms of disease: neuropathic pain--a clinical perspective. Nat Clin Pract Neurol 2006; 2(2): 95-106.
3. Gangadhar M, Mishra RK, Sriram D, Yogeeswari P. Future directions in the treatment of neuropathic pain: a review on various therapeutic targets. CNS Neurol Disord Drug Targets 2014; 13(1): 63-81.
4. Merskey H, Bogduk N. Classification of chronic pain: Descriptions of chronic pain syndromes and definitions of pain terms. Seattle, WA: IASP Press; 1994.
5. Davies M, Brophy S, Williams R, Taylor A. The prevalence, severity, and impact of painful diabetic peripheral neuropathy in type 2 diabetes. Diabetes Care 2006; 29(7): 1518-22.
6. Abbott CA, Malik RA, van Ross ER, Kulkarni J, Boulton AJ. Prevalence and characteristics of painful diabetic neuropathy in a large community-based diabetic population in the U.K. Diabetes Care 2011; 34(10): 2220-4.
7. Galer BS, Gianas A, Jensen MP. Painful diabetic polyneuropathy: Epidemiology, pain description, and quality of life. Diabetes Res Clin Pract 2000; 47(2): 123-8.
8. Callaghan BC, Little AA, Feldman EL, Hughes RA. Enhanced glucose control for preventing and treating diabetic neuropathy. Cochrane Database Syst Rev 2012; (6): CD007543.
9. Snyder MJ, Gibbs LM, Lindsay TJ. Treating painful diabetic peripheral neuropathy: An update. Am Fam Physician 2016; 94(3): 227-34.
10. Tankisi H, Pugdahl K, Fuglsang-Frederiksen A, Johnsen B, de Carvalho M, Fawcett PR, et al. Pathophysiology inferred from electrodiagnostic nerve tests and classification of polyneuropathies. Suggested guidelines. Clin Neurophysiol 2005; 116(7): 1571-80.
11. Jensen MP, Friedman M, Bonzo D, Richards P. The validity of the neuropathic pain scale for assessing diabetic neuropathic pain in a clinical trial. Clin J Pain 2006; 22(1): 97-103.
12. Boulton AJ, Kirsner RS, Vileikyte L. Clinical practice. Neuropathic diabetic foot ulcers. N Engl J Med 2004; 351(1): 48-55.
13. Kiani J, Moghimbeigi A, Azizkhani H, Kosarifard S. The prevalence and associated risk factors of peripheral diabetic neuropathy in Hamedan, Iran. Arch Iran Med 2013; 16(1): 17-9.
14. Rahimdel A, Afkhami-Ardekani M, Souzani A, Modaresi M, Mashahiri MR. Prevalence of sensory neuropathy in type 2 diabetic patients in Iranian population (Yazd Province). Iran J diabetes Obes 2009; 1(1): 30-5. [In Persian].
15. Baharvand P, Moazami Ghoodarzi H, Moarefzade M. The prevalence of peripheral neuropathy in diabetic Patients of Khorramabad diabetes center in 2015. Yafte 2015; 17(2): 51-9. [In Persian].
16. Daousi C, MacFarlane IA, Woodward A, Nurmikko TJ, Bundred PE, Benbow SJ. Chronic painful peripheral neuropathy in an urban community: A controlled comparison of people with and without diabetes. Diabet Med 2004; 21(9): 976-82.
17. Dworkin RH, O'Connor AB, Backonja M, Farrar JT, Finnerup NB, Jensen TS, et al. Pharmacologic management of neuropathic pain: Evidence-based recommendations. Pain 2007; 132(3): 237-51.
18. Ziegler D. Painful diabetic neuropathy: Treatment and future aspects. Diabetes Metab Res Rev 2008; 24(Suppl 1): S52-S57.
19. Finnerup NB, Sindrup SH, Jensen TS. Recent advances in pharmacological treatment of neuropathic pain. F1000 Med Rep 2010; 2: 52.
20. Gilio F, Iacovelli E, Frasca V, Gabriele M, Giacomelli E, Picchiori F, et al. Botulinum toxin type A for the treatment of sialorrhoea in amyotrophic lateral sclerosis: a clinical and neurophysiological study. Amyotroph Lateral Scler 2010; 11(4): 359-63.
21. Relja M, Klepac N. Different doses of botulinum toxin A and pain responsiveness in cervical dystonia. Neurology 2002; 58: A474.
22. Paterson K, Lolignier S, Wood JN, McMahon SB, Bennett DL. Botulinum toxin-A treatment reduces human mechanical pain sensitivity and mechanotransduction. Ann Neurol 2014; 75(4): 591-6.
23. Dolly JO, O'Connell MA. Neurotherapeutics to inhibit exocytosis from sensory neurons for the control of chronic pain. Curr Opin Pharmacol 2012; 12(1): 100-8.
24. Moon YE, Choi JH, Park HJ, Park JH, Kim JH. Ultrasound-guided nerve block with botulinum toxin type a for intractable neuropathic pain. Toxins (Basel) 2016; 8(1).
25. Nam KE, Kim JS, Hong BY, Sul B, Choi H, Jun SY, et al. Botulinum toxin type A injection for neuropathic pain in a patient with a brain tumor: A case report. Ann Rehabil Med 2017; 41(6): 1088-92.
26. Park J, Park HJ. Botulinum toxin for the treatment of neuropathic pain. Toxins (Basel) 2017; 9(9).
27. Han ZA, Song DH, Oh HM, Chung ME. Botulinum toxin type A for neuropathic pain in patients with spinal cord injury. Ann Neurol 2016; 79(4): 569-78.
28. Madani SP, Fateh HR, Forogh B, Fereshtehnejad SM, Ahadi T, Ghaboussi P, et al. Validity and reliability of the Persian (Farsi) version of the DN4 (Douleur Neuropathique 4 Questions) questionnaire for differential diagnosis of neuropathic from non-neuropathic pains. Pain Pract 2014; 14(5): 427-36.
29. Bouhassira D, Attal N, Alchaar H, Boureau F, Brochet B, Bruxelle J, et al. Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 2005; 114(1-2): 29-36.
30. Chatterjee S, Sanyal D, Das Choudhury S, Bandyopadhyay M, Chakraborty S, Mukherjee A. Effect of pioglitazone on nerve conduction velocity of the median nerve in the carpal tunnel in type 2 diabetes patients. World J Diabetes 2016; 7(19): 547-53.
31. Yuan RY, Sheu JJ, Yu JM, Chen WT, Tseng IJ, Chang HH, et al. Botulinum toxin for diabetic neuropathic pain: a randomized double-blind crossover trial. Neurology 2009; 72(17): 1473-8.
32. Ghasemi M, Ansari M, Basiri K, Shaigannejad V. The effects of intradermal botulinum toxin type a injections on pain symptoms of patients with diabetic neuropathy. J Res Med Sci 2014; 19(2): 106-11.
33. Jhang JF, Kuo HC. Novel treatment of chronic bladder pain syndrome and other pelvic pain disorders by onabotulinumtoxina injection. Toxins (Basel) 2015; 7(6): 2232-50.
34. Montazeri A, Goshtasebi A, Vahdaninia M, Gandek B. The Short Form Health Survey (SF-36): Translation and validation study of the Iranian version. Qual Life Res 2005; 14(3): 875-82.
35. Said G. Focal and multifocal diabetic neuropathies. Arq Neuropsiquiatr 2007; 65(4B): 1272-8.
36. Turk DC, Melzack R. The measurement of pain and the assessment of people experiencing pain. In: Turk DC, Melzack R, editors. Handbook of pain assessment. 2nd ed. New York, NY: The Guilford Press; 2001. p. 1-11.
37. Jensen MP, Karoly P, Braver S. The measurement of clinical pain intensity: A comparison of six methods. Pain 1986; 27(1): 117-26.
38. Farrahi MJ, Nakhaee N, Sheibani V, Garrusi B, Amirkafi A. Reliability and validity of the Persian version of the Pittsburgh Sleep Quality Index (PSQI-P). Sleep Breath 2012; 16(1): 79-82.
39. Zdravkovic V, Daneman D, Hamilton J. Presentation and course of Type 2 diabetes in youth in a large multi-ethnic city. Diabet Med 2004; 21(10): 1144-8.
40. Congdon P. Estimating diabetes prevalence by small area in England. J Public Health (Oxf) 2006; 28(1): 71-81.
41. Lin SF, Lin JD, Huang YY. Diabetic ketoacidosis: Comparisons of patient characteristics, clinical presentations and outcomes today and 20 years ago. Chang Gung Med J 2005; 28(1): 24-30.
42. Sadosky A, Schaefer C, Mann R, Bergstrom F, Baik R, Parsons B, et al. Burden of illness associated with painful diabetic peripheral neuropathy among adults seeking treatment in the US: Results from a retrospective chart review and cross-sectional survey. Diabetes Metab Syndr Obes 2013; 6: 79-92.
43. Pavone F, Luvisetto S. Botulinum neurotoxin for pain management: insights from animal models. Toxins (Basel) 2010; 2(12): 2890-913.
44. Francisco GE, Tan H, Green M. Do botulinum toxins have a role in the management of neuropathic pain?: A focused review. Am J Phys Med Rehabil 2012; 91(10): 899-909.
45. Lakhan SE, Velasco DN, Tepper D. Botulinum toxin-A for painful diabetic neuropathy: A meta-analysis. Pain Med 2015; 16(9): 1773-80.
46. Ding XD, Zhong J, Liu YP, Chen HX. Botulinum as a toxin for treating post-herpetic Neuralgia. Iran J Public Health 2017; 46(5): 608-11.
47. Binay Safer V, Ozbudak Demir S, Ozkan E, Demircioglu Guneri F. Effects of botulinum toxin serotype A on sleep problems in children with cerebral palsy and on mothers sleep quality and depression. Neurosciences (Riyadh) 2016; 21(4): 331-7.
How to Cite
Salehi H, Moussaei M, Kamiab Z, Vakilian A. The effects of botulinum toxin type A injection on pain symptoms, quality of life, and sleep quality of patients with diabetic neuropathy: A randomized double-blind clinical trial. Iran J Neurol. 18(3):99-107.
Original Article(s)