The use of botulinum neuropeptide in gynecology

DOI

https://dx.doi.org/10.18565/aig.2023.282

Sokolova A.V., Ushakova K.A., Apolikhina I.A.
Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, Moscow, Russia

Botulinum toxin is a high-molecular protein complex produced by bacteria of the Clostridium genus. It is one of the most powerful organic poisons. Nevertheless, botulinum toxin has become widely used in medical practice due to its unique properties. There are several serotypes of the neurotoxin: BT-A, BT-B, BT-C, BT-D, BT-E, BT-F, BT-G, B-X, and non-clostridial nature: BT-Wo, BT-En. The most common one is botulinum toxin type A which blocks the release of certain neurotransmitters at the neuromuscular junction and leads to a temporary decrease in muscle activity. Botulinum toxin type A has been used for more than 20 years for the symptomatic treatment of various conditions associated with excessive muscle activity. Moreover, botulinum toxin is known as an effective and fast-acting substance in the treatment of chronic pain due to its antinociceptive (analgesic) and anti-inflammatory properties. Recently, the researchers have become particularly interested in the use of botulinum toxin in gynecology, especially in the treatment of diseases such as pelvic floor muscle hyperactivity and vaginismus, vulvodynia and chronic pelvic pain, when first-line therapy is ineffective. Despite the fact that these diseases are not life-threatening, they significantly reduce the quality of patients’ lives. For clinicians who regularly deal with these clinical cases, botulinum toxin type A becomes a valuable medication in the treatment of difficult patients when traditional methods are ineffective.
Conclusion: Different mechanisms of botulinum toxin action as well as the latest research in the field of neurogynecology are considered in this article. The literature review includes publications confirming the effectiveness and safety of the use of this neuropeptide for the treatment of conditions associated with increased tone of the pelvic floor muscles. However, it is necessary to conduct further research for determining the optimal dosages, treatment regimens and evaluation of the long-term efficacy and safety of botulinum toxin in gynecology.

Authors’ contributions: Sokolova A.V. – review of publications on the issue of the article, writing the text, editing the text; Ushakova K.A. – review of publications on the issue of the article, writing the text; Apolikhina I.A. – editing the article.
Conflicts of interest: The authors declare no possible conflicts of interest.
Funding: The study was conducted without sponsorship.
For citation: Sokolova A.V., Ushakova K.A., Apolikhina I.A. The use of botulinum neuropeptide in gynecology.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2024; (3): 28-34 (in Russian)
https://dx.doi.org/10.18565/aig.2023.282

botulinum therapy

botulinum toxin

neuropeptide

vaginismus

chronic pelvic pain

pelvic floor hypertonicity

botulinum therapy in gynecology

neurogynecology

Full text (in Russian)

Каприн А.Д., Аполихин О.И., Алексеев Б.Я., Сивков А.В., Ромих В.В., Захарченко А.В., Пантелеев В.В., Ромих Ф.Д. Ботулинотерапия в современной урологии. Медицинский совет. 2016; 10: 130-9. [Kaprin A.D., Apolikhin O.I., Alekseev B.Ya., Sivkov A.V., Romikh V.V., Zakharchenko A.V., Panteleev V.V., Romikh F.D. Botulinum in modern urology. Medical Council. 2016; (10): 130-9. (in Russian)]. https://dx.doi.org/10.21518/2079-701X-2016-10-130-139.
Jarvis S.K., Abbott J.A., Lenart M.B., Steensma A., Vancaillie T.G. Pilot study of botulinum toxin type A in the treatment of chronic pelvic pain associated with spasm of the levator ani muscles. Aust. N. Z. J. Obstet. Gynaecol. 2004; 44(1): 46-50. https://dx.doi.org/10.1111/j.1479-828X.2004.00163.x.
Pirazzini M., Rossetto O., Eleopra R., Montecucco C. Botulinum neurotoxins: biology, pharmacology and toxicology. Pharmacol. Rev. 2017; 69(2): 200-35. https://dx.doi.org/10.1124/pr.116.012658.
Rossetto O., Pirazzini M., Montecucco C. Botulinum neurotoxins: genetic, structural and mechanistic insights. Nat. Rev. Microbiol. 2014; 12(8): 535-49. https://dx.doi.org/10.1038/nrmicro3295.
Hill K.K., Smith T.J. Genetic diversity within Clostridium botulinum serotypes, botulinum neurotoxin gene clusters and toxin subtypes. Curr. Top. Microbiol. Immunol. 2013; 364: 1-20. https://dx.doi.org/10.1007/978-3-642-33570-9_1.
Burke G.S. Notes on Bacillus botulinus. J. Bacteriol. 1919; 4(5): 555-70.1. https://dx.doi.org/10.1128/jb.4.5.555-570.1.1919.
Gimenez D.F., Ciccarelli A.S. Another type of Clostridium botulinum. Zentralbl. Bakteriol. Orig. 1970; 215(2): 221-4.
Chai Q., Arndt J.W., Dong M., Tepp W.H., Johnson E.A., Chapman E.R. et al. Structural basis of cell surface receptor recognition by botulinum neurotoxin B. Nature. 2006; 444(7122): 1096-100. https://dx.doi.org/10.1038/nature05411.
Эрнандес Е.И., ред. Новая косметология. Инъекционные методы в косметологии. М.: ИД «Косметика и медицина»; 2014: 126-71. [Hernandez E.I., ed. New cosmetology. Injectable methods in cosmetology. Moscow: Publishing House "Cosmetics and Medicine"; 2014: 126-71. (in Russian)].
Kukreja R., Singh B.R. The botulinum toxin as a therapeutic agent: molecular and pharmacological insights. Res. Rep. Biochem. 2015; 5(1): 173-83. https://dx.doi.org/10.2147/RRBC.S60432.
Pellizzari R., Rossetto O., Schiavo G., Montecucco C. Tetanus and botulinum neurotoxins: mechanism of action and therapeutic uses. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 1999; 354(1381): 259-68. https://dx.doi.org/10.1098/rstb.1999.0377.
Azarnia Tehran D., Pirazzini M., Leka O., Mattarei A., Lista F., Binz T. et al. Hsp90 is involved in the entry of clostridial neurotoxins into the cytosol of nerve terminals. Cell. Microbiol. 2017; 19(2): e12647. https://dx.doi.org/10.1111/cmi.12647.
Montal M. Botulinum neurotoxin: a marvel of protein design. Annu. Rev. Biochem. 2010; 79: 591-617. https://dx.doi.org/10.1146/annurev.biochem.051908.125345.
Park J., Park H.J. Botulinum toxin for the treatment of neuropathic pain. Toxins (Basel). 2017; 9(9): 260. https://dx.doi.org/10.3390/toxins9090260.
Shin M.C., Wakita M., Xie D.J., Yamaga T., Iwata S., Torii Y. et al. Inhibition of membrane Na+ channels by A type botulinum toxin at femtomolar concentrations in central and peripheral neurons. J. Pharmacol. Sci. 2012; 118(1): 33-42. https://dx.doi.org/10.1254/jphs.11060fp.
Naumann M., Albaneseb A., Heinenc F., Molenaersd G., Relja M. Safety and efficacy of botulinum toxin type A following long-term use. Eur. J. Neurol. 2006; 13(Suppl. 4): 35-40. https://dx.doi.org/10.1111/j.1468-1331.2006.01652.x.
Reissing E.D. Vaginismus: evaluation and management. In: Goldstein A.T., Pukall C.F., Goldstein I., eds. Female sexual pain disorders. Willey-Blackwell, a John Wiley and Sons, LTD, Publication; 2009: 229-34. https://dx.doi.org/10.1002/9781444308136.ch35.
Pacik P.T., Geletta S. Vaginismus treatment: clinical trials follow up 241 patients. Sex. Med. 2017; 5(2): e114-e123. https://dx.doi.org/10.1016/j.esxm.2017.02.002.
Lamont J.A. Vaginismus. Am. J. Obstet. Gynecol. 1978; 131(6): 633-6.
Shafik A., El-Sibai O. Study of the pelvic floor muscles in vaginismus: a concept of pathogenesis. Eur. J. Obstet. Gynecol. Reprod. Biol. 2002; 105(1): 67-70. https://dx.doi.org/10.1016/s0301-2115(02)00115-x.
Banaei M., Kariman N., Ozgoli G., Nasiri M. Bio-psychosocial factor of vaginismus in Iranian women. Reprod. Health. 2021; 18(1): 210. https://dx.doi.org/10.1186/s12978-021-01260-2.
Pacik P.T. Understanding and treating vaginismus: a multimodal approach. Int. Urogynecol. J. 2014; 25(12): 1613-20. https://dx.doi.org/10.1007/s00192-014-2421-y.
Reissing E.D., Binik Y.M., Khalife S., Cohen D., Amsel R. Etiological correlates of vaginismus: sexual and physical abuse, sexual knowledge, sexual self-schema, and relationship adjustment. J. Sex Marital Ther. 2003; 29(1): 47-59. https://dx.doi.org/10.1080/713847095.
Lahaie M.A., Boyer S.C., Amsel R., Khalife S., Binik Y.M. Vaginismus: a review of the literature on the classification/diagnosis, etiology and treatment. Womens Health (Lond). 2010; 6(5): 705-19. https://dx.doi.org/10.2217/whe.10.46.
Pacik P.T. Vaginismus: review of current concepts and treatment using botox injections, bupivacaine injections, and progressive dilation with the patient under anesthesia. Aesthetic Plast. Surg. 2011; 35(6): 1160-4. https://dx.doi.org/10.1007/s00266-011-9737-5.
Ghazizadeh S., Nikzad M. Botulinum toxin in the treatment of refractory vaginismus. Obstet. Gynecol. 2004; 104(5 Pt. 1): 922-5. https://dx.doi.org/10.1097/01.AOG.0000141441.41178.6b.
Brin M.F., Vapnek J.M. Treatment of vaginismus with botulinum toxin injections. Lancet. 1997; 349(9047): 252-3. https://dx.doi.org/10.1016/S0140-6736(05)64862-3.
Shafik A., El-Sibai O. Vaginismus: results of treatment with botulin toxin. J. Obstet. Gynaecol. 2000; 20(3): 300-2. https://dx.doi.org/10.1080/01443610050009674.
Petersen C.D., Giraldi A., Lundvall L., Kristensen E. Botulinum toxin type A - a novel treatment for provoked vestibulodynia? Results from a randomized, placebo controlled, double blinded study. J. Sex. Med. 2009; 6(9): 2523-37. https://dx.doi.org/10.1111/j.1743-6109.2009.01378.x.
Goldstein A.T., Marinoff S.C., Haefner H.K. Vulvodynia: strategies for treatment. Clin. Obstet. Gynecol. 2005; 48(4): 769-85. https://dx.doi.org/10.1097/01.grf.0000182213.21599.49.
Goldstein A.T., Pukall C.F. Provoked vestibulodynia. In: Goldstein A.T., Pukall C.F., Goldstein I., eds. Female sexual pain disorders. Willey-Blackwell, a John Wiley and Sons, LTD, Publication; 2009: 43-8. https://dx.doi.org/10.1002/9781444308136.ch8.
Pelletier F., Parratte B., Penz S., Moreno J.P., Aubin F., Humbert P. Efficacy of high doses of botulinum toxin A for treating provoked vestibulodynia. Br. J. Dermatol. 2011; 164(3): 617-22. https://dx.doi.org/10.1111/j.1365-2133.2011.10235.x.
Yoon H., Chung W.S., Shim B.S. Botulinum toxin A for the management of vulvodynia. Int. J. Impot. Res. 2007; 19(1): 84-7. https://dx.doi.org/10.1038/sj.ijir.3901487.
Speer L.M., Mushkabar S., Erbele T. Chronic pelvic pain in women. Am. Fam. Physician. 2016; 93(5): 380-7.
Тетерина Т.А., Аполихина И.А. Синдром хронической тазовой боли в практике врача-гинеколога (алгоритмы диагностики лечения). Акушерство и гинекология. 2019; 12(Приложение): 24-30. [Teterina T.A., Apolikhina I.A. Chronic pelvic pain syndrome in the practice of a gynecologist (diagnostic and treatment algorithms). Obstetrics and Gynecology. 2019; (12 Suppl.): 24-30 (in Russian)]. https://dx.doi.org/10.18565/aig.2019.12suppl.24-30.
As-Sanie S., Till S.R., Schrepf A.D., Griffith K.C., Tsodikov A., Missmer S.A. et al. Incidence and predictors of persistent pelvic pain following hysterectomy in women with chronic pelvic pain. Am. J. Obstet. Gynecol. 2021; 225(5): 568.e1-568.e11. https://dx.doi.org/10.1016/j.ajog.2021.08.038.
Jarrell J.F., Vilos G.A., Allaire C., Burgess S., Fortin C., Gerwin R. et al. Consensus guidelines for the management of chronic pelvic pain. J. Obstet. Gynaecol. Can. 2005; 27(8): 781-826. https://dx.doi.org/10.1016/s1701-2163(16)30732-0.
Akour A., Kasabri V., Afifi F.U., Bulatova N. The use of medicinal herbs in gynecological and pregnancy-related disorders by Jordanian women: a review of folkloric practice vs. evidence-based pharmacology. Pharm. Biol. 2016; 54(9): 1901-18. https://dx.doi.org/10.3109/13880209.2015.1113994.
Abbott J.A., Jarvis S.K., Lyons S.D., Thomson A., Vancaille T.G. Botulinum toxin type A for chronic pain and pelvic floor spasm in women: a randomized controlled trial. Obstet. Gynecol. 2006; 108(4): 915-23. https://dx.doi.org/10.1097/01.AOG.0000237100.29870.cc.
Adelowo A., Hacker M.R., Shapiro A., Modest A.M., Elkadry E. Botulinum toxin type A (BOTOX) for refractory myofascial pelvic pain. Female Pelvic Med. Reconstr. Surg. 2013; 19(5): 288-92. https://dx.doi.org/10.1097/SPV.0b013e3182989fd8.
Thomson A.J., Jarvis S.K., Lenart M., Abbott J.A., Vancaillie T.G. The use of botulinum toxin type A (Botox) as treatment for intractable chronic pelvic pain associated with spasm of the levator ani muscles. BJOG. 2005; 112(2): 247-9. https://dx.doi.org/10.1111/j.1471-0528.2004.00315.x.

Received 07.12.2023

Accepted 07.03.2024

Anastasia V. Sokolova, MD, obstetrician-gynecologist, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology,
Ministry of Health of Russia, 4, Oparina str., Moscow, 117997, Russia, +7(915)455-31-32, stasia0590@mail.ru
Kseniia A. Ushakova, student, Pirogov Russian National Research Medical University, Ministry of Health of Russia, 1, Ostrovityanova str., Moscow,
117997, Russia, +7(925)379-33-03, x.ushakova1468@bk.ru
Inna A. Apolikhina, Dr. Med. Sci., Professor, Head of the Department of Aesthetic Gynecology and Rehabilitation, V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia; Professor at the Department of Obstetrics, Gynecology, Perinatology, and Reproductology,
Institute of Professional Education, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, +7(495)735-10-55, apolikhina@inbox.ru,
https://orcid.org/0000-0002-4581-6295, 117997, Russia, Moscow, Ac. Oparina str., 4.

The use of botulinum neuropeptide in gynecology

Sokolova A.V., Ushakova K.A., Apolikhina I.A.

Keywords

References

About the Authors

Similar Articles