Botulinum toxin treatment of neuropathic pain

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Neuropathic pain appears to be an actual medical and social issue. Pharmacological and neurosurgical treatment methods do not always lead to effective pain relief. The aim of this review is to summarize clinical data on the antinociceptive effects and clinical use of BTA in patients with central and peripheral neuropathic pain. We searched for RCTs, systematic reviews, and meta-analyzes on the subject in the PubMed and OvidSP databases from 2008 to February 2020. BTA injections may be beneficial for patients with neuropathic pain, when pharmacotherapy is ineffective, insufficiently effective or cannot be used. Botulinum toxin may be used as a multi-purpose drug for these patients due to its clinical efficacy, favorable safety profile and long-term pain relief effecr after a single injection. At the same time, BTA injections are referred to the third-line drugs and further large-scale, carefully conducted clinical studies are needed to increase the recommendations level for the BTA use in terms of the neuropathic pain treatment.

Keywords:

neuropathic pain

Botulinum toxin type A

neuropathic pain treatment

botulinum toxin for neuropathic pain

neuropathic pain botulinum therapy

Authors:

Medvedeva L.A.

FGBU "RNTsKh im. akad. B.V. Petrovskogo" RAMN

Zagorulko O.I.

Petrovsky Russian Research Center of Surgery

ORCID: 0000-0002-2713-9577

Shevtsova G.E.

Sechenov First Moscow State Medical University, Moscow

Received:

22.04.2020

Accepted:

29.04.2020

Conflict of Interest :

The authors declare no conflicts of interest.

List of references:

Jensen TS, Baron R, Haanpää M, Kalso E, Loeser JD, Rice AS, Treede RD. A new definition of neuropathic pain. Pain. 2011;152(10):2204-2205. https://doi.org/10.1016/j.pain.2011.06.017
Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, Gilron I, Haanpää M, Hansson P, Jensen TS, Kamerman PR, Lund K, Moore A, Raja SN, Rice AS, Rowbotham M, Sena E, Siddall P, Smith BH, Wallace M. Pharmacotherapy for neuropathic pain in adults: A systematic review and meta‐analysis. The Lancet Neurology. 2015;14(2):162-173. https://doi.org/10.1016/S1474-4422(14)70251-0
van Hecke O, Austin SK, Khan RA, Smith BH, Torrance N. Neuropathic pain in the general population: A systematic review of epidemiological studies. Pain. 2014;155(4):654-662. https://doi.org/10.1016/j.pain.2013.11.013
Yakhno NN, Kukushkin ML, Danilov AB, Amelin AV, Davydov OS, Kulikov SM. Results of the Russian epidemiological study of neuropathic pain, its causes and characteristics in the population of outpatients who turned to a neurologist. Bol’. 2008;3(20):24-32. (In Russ.).
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;29:1518-1522. https://doi.org/10.2337/dc05-2228
Kiyani M, Yang Z, Charalambous LT, Adil SM, Lee H, Yang S, Pagadala P, Parente B, Spratt SE, Lad SP. Painful diabetic peripheral neuropathy: Health care costs and complications from 2010 to 2015. Neurology: Clinical Practice. 2020;10(1):47-57. https://doi.org/10.1212/CPJ.0000000000000671
Hetmann F, Kongsgaard UE, Sandvik L, Schou-Bredal I. Post-thoracotomy pain syndrome and sensory disturbances following thoracotomy at 6- and 12-month follow-ups. Journal of Pain Research. 2017;10:663-668. https://doi.org/10.2147/JPR.S126639
Medvedeva LA, Zagorulko OI, Churukanov MV, Davydov O.S. Neuropathic pain after surgery. Rossijskij zhurnal boli. 2018;1(55):7-13. (In Russ.).
Heitmann H, Biberacher V, Tiemann L, Buck D, Loleit V, Selter RC, Knier B, Tölle TR, Mühlau M, Berthele A, Hemmer B, Ploner M. Prevalence of neuropathic pain in early multiple sclerosis. Multiple Sclerosis. 2016;22(9):1224-1230. https://doi.org/10.1177/1352458515613643
Yoon SY, Oh J. Neuropathic cancer pain: Prevalence, pathophysiology, and management. The Korean Journal of Internal Medicine. 2018;33(6):1058-1069. https://doi.org/10.3904/kjim.2018.162
Freynhagen R, Baron R, Tölle T, Stemmler E, Gockel U, Stevens M, Maier C. Screening of neuropathic pain components in patients with chronic back pain associated with nerve root compression: a prospective observational pilot study (MIPORT). Current Medical Research and Opinion. 2006;22(3):529-537. https://doi.org/10.1185/030079906X89874
Davydov OS, Yakhno NN, Kukushkin ML, Churyukanov MV, Abuzarova GR, Amelin AV, Balyazin VA, Barantsevich ER, Barinov AN, Barulin AE, Belskaya GN, Bykov YuN, Danilov AB, Doronina OB, Dreval ON, Evseev MA, Zagorulko OI, Isagulyan ED, Kalinsky PP, Karakulova YuV, Karateev AE, Kopenkin SS, Kurushina OV, Medvedeva LA, Parfenov VA, Sergienko DA, Strokov IA, Khabirov FA, Shirokov VA. Neuropathic pain: clinical guidelines for the diagnosis and treatment of the Russian Society for the Study of Pain. Rossijskij zhurnal boli. 2018;4(58):5-41. (In Russ). https://doi.org/10.25731/RASP.2018.04.025
Hansson PT, Attal N, Baron R, Cruccu G. Toward a definition of pharmacoresistant neuropathic pain. European Journal of Pain. 2009;13(5):439-440. https://doi.org/10.1016/j.ejpain.2009.02.008
Freynhagen R, Serpell M, Emir B, Whalen E, Parsons B, Clair A, Latymer M. A comprehensive drug safety evaluation of pregabalin in peripheral neuropathic pain. Pain Practice. 2015;15(1):47-57. https://doi.org/10.1111/papr.12146
Wei J, Zhu X, Yang G, Shen J, Xie P, Zuo X, Xia L, Han Q, Zhao Y. The efficacy and safety of botulinum toxin type A in treatment of trigeminal neuralgia and peripheral neuropathic pain: A meta-analysis of randomized controlled trials. Brain and Behavior. 2019;9(10):01409. https://doi.org/10.1002/brb3.1409
Aoki KR. Review of a Proposed Mechanism for the Antinociceptive Action of Botulinum Toxin Type A. Neurotoxicology. 2005;26:785-793. https://doi.org/10.1016/j.neuro.2005.01.017
Jeynes LC, Gauci CA. Evidence for the use of botulinum toxin in the chronic pain setting: A review of the literature. Pain Practice. 2008;8:269-276. https://doi.org/10.1111/j.1533-2500.2008.00202.x
Cui M, Khanijou S, Rubino J, Aoki KR. Subcutaneous administration of botulinum toxin A reduces formalin-induced pain. Pain. 2004;107:125-133. https://doi.org/10.1016/j.pain.2003.10.008
Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, Schünemann HJ. GRADE: An emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336:924-926. https://doi.org/10.1136/bmj.39489.470347.AD
AGREE Collaboration. Development and validation of an international appraisal instrument for assessing the quality of clinical practice guidelines: the AGREE project. Quality and Safety in Health Care. 2003;12(1):18-23. https://doi.org/10.1136/qhc.12.1.18
Meng F, Peng K, Yang JP, Ji FH, Xia F, Meng XW. Botulinum toxin-A for the treatment of neuralgia: a systematic review and meta-analysis. Journal of Pain Research. 2018;11:2343-2351. https://doi.org/10.2147/JPR.S168650
Mittal SO, Safarpour D, Jabbari B. Botulinum Toxin Treatment of Neuropathic Pain. Seminars in Neurology. 2016;36(1):73-83. https://doi.org/10.1055/s-0036-1571953
Safarpour Y, Jabbari B. Botulinum toxin treatment of pain syndromes — an evidence based review. Toxicon. 2018;147:120-128. https://doi.org/10.1016/j.toxicon.2018.01.017
Ranoux D, Attal N, Morain F, Bouhassira D. Botulinum toxin type A induces direct analgesic effects in chronic neuropathic pain. Annals of Neurology. 2008;64:274-283. https://doi.org/10.1002/ana.21427
Xiao L, Mackey S, Hui H, Xong D, Zhang Q, Zhang D. Subcutaneous injection of botulinum toxin A is beneficial in postherpetic neuralgia. Pain Medicine. 2010;11:1827-1833. https://doi.org/10.1111/j.1526-4637.2010.01003.x
Zhang H, Lian Y, Ma Y, Chen Y, He C, Xie N, Wu C. Two doses of botulinum toxin type A for the treatment of trigeminal neuralgia: observation of therapeutic effect from a randomized, double-blind, placebo-controlled trial. The Journal of Headache and Pain. 2014;15(1):65. https://doi.org/10.1186/1129-2377-15-65
Attal N, de Andrade DC, Adam F, Ranoux D, Teixeira MJ, Galhardoni R, Raicher I, Üçeyler N, Sommer C, Bouhassira D. Safety and efficacy of repeated injections of botulinum toxin A in peripheral neuropathic pain (BOTNEP): a randomised, double-blind, placebo-controlled trial. The Lancet Neurology. 2016;15(6):555-565. https://doi.org/10.1016/S1474-4422(16)00017-X
Li XL, Zeng X, Zeng S, He HP, Zeng Z, Peng LL, Chen LG. Botulinum toxin A treatment for post-herpetic neuralgia: A systematic review and meta-analysis. Experimental and Therapeutic Medicine. 2020;19(2):1058-1064. https://doi.org/10.3892/etm.2019.8301
Breuer B, Sperber K, Wallenstein S, Kiprovski K, Calapa A, Snow B, Pappagallo M. Clinically Significant Placebo Analgesic Response in a Pilot Trial of Botulinum B in Patients with Hand Pain and Carpal Tunnel Syndrome. Pain Medicine. 2006;7(1):16-24. https://doi.org/10.1111/j.1526-4637.2006.00084.x
Juan-García FJ, Formigo-Couceiro J, Barrio-Alonso M, Ouviña-Arribas R. Effectiveness of botulinum toxin type a in carpal tunnel syndrome. Musculoskeletal Research. 2016;19(2):1650006. https://doi.org/10.1142/S0218957716500068
Shymaa A, Hablas SA, Nada DW, Alashkar DS, Elsharkawy AA. The effect of botulinum toxin type A injection in decreasing intratunnel tendon tension in carpal tunnel syndrome: a randomized controlled trial for efficacy and safety. Egyptian Rheumatology and Rehabilitation. 2019;46(4):299-303.
Yuan RY, Sheu JJ, Yu JM, Chen WT, Tseng IJ, Chang HH, Hu CJ. Botulinum toxin for diabetic neuropathic pain A randomized double-blind crossover trial. Neurology. 2009;72(17):1473-1478. https://doi.org/10.1212/01.wnl.0000345968.05959.cf
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. Iranian Journal of Neurology. 2019;18(3):99-107.
Lakhan SE, Velasco DN, Tepper D. Botulinum Toxin-A for Painful Diabetic Neuropathy: A Meta-Analysis. Pain Medicine. 2015;16(9):1773-1780. https://doi.org/10.1111/pme.12728
Fabregat G, Asensio-Samper JM, Palmisani S, Villanueva-Pérez VL, De Andrés J. Subcutaneous botulinum toxin for chronic post-thoracotomy pain. Pain Practice: the Official Journal of World Institute of Pain. 2013;13(3):231-234. https://doi.org/10.1111/j.1533-2500.2012.00569.x
Smoot D, Zielinski M, Jenkins D, Schiller H. Botox A injection for pain after laparoscopic ventral hernia: a case report. Pain Medicine. 2011;12(7):1121-1123. https://doi.org/10.1111/j.1526-4637.2011.01147.x
Yang KY, Kim MJ, Ju JS, Park SK, Lee CG, Kim ST, Bae YC, Ahn DK. Antinociceptive Effects of Botulinum Toxin Type A on Trigeminal Neuropathic Pain. Dental Research. 2016;95(10):1183-1190. https://doi.org/10.1177/0022034516659278
Hamdy RC, Montpetit K, Aiona MD, MacKenzie WG, van Bosse HJ, Narayanan U, Raney EM, Chafetz RS, Thomas SE, Weir S, Gregory S, Yorgova P, Takahashi S, Rinaldi M, Zhang X, Dahan-Oliel N. Safety and Efficacy of Botulinum Toxin A in Children Undergoing Lower Limb Lengthening and Deformity Correction: Results of a Double-blind, Multicenter, Randomized Controlled Trial. Journal of Pediatric Orthopedics. 2016;36(1):48-55. https://doi.org/10.1097/BPO.0000000000000398
Tandon HK, Stratton P, Sinaii N, Shach J, Karp BL. Botulinum toxin for chronic pelvic pain in women with endometriosis: a cohort study of a pain-focused treatment. Regional Anesthesia and Pain Medicine. 2019;44:886-892. https://doi.org/10.1136/rapm-2019-100529
Karp BI, Tandon H, Vigil D, Stratton P. Methodological approaches to botulinum toxin for the treatment of chronic pelvic pain, vaginismus, and vulvar pain disorders. International Urogynecology Journal. 2019;30:1071-1081. https://doi.org/10.1007/s00192-018-3831-z
Diomande I, Gabriel N, Kashiwagi M, Ghisu GP, Welter J, Fink D, Fehr MK, Betschart C. Subcutaneous botulinum toxin type A injections for provoked vestibulodynia: A randomized placebo-Controlled trial and exploratory subanalysis. Archives of Gynecology and Obstetrics. 2019;299:993-1000. https://doi.org/10.1007/s00404-019-05043-w
Wells C, Farrah K. Injectable Botulinum Toxin for Pelvic Pain: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2019 Aug 22. Available at: https://www.nc Accessed April 20, 2020
Han ZA, Song DH, Oh HM, Chung ME. Botulinum toxin type A for neuropathic pain in patients with spinal cord injury. Annals of Neurology. 2016;79:569-578. https://doi.org/10.1002/ana.24605
Intiso D, Basciani M, Santamato A, Intiso M, Di Rienzo F. Botulinum Toxin Type A for the Treatment of Neuropathic Pain in Neuro-Rehabilitation. Toxins. 2015;7:2454-2480. https://doi.org/10.3390/toxins7072454

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