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Botulinum Toxin in Chronic Pelvic Pain Management

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Chronic Pelvic Pain and Pelvic Dysfunctions

Part of the book series: Urodynamics, Neurourology and Pelvic Floor Dysfunctions ((UNPFD))

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Abstract

Botulinum toxins are a large family of proteins produced by a gram-positive anaerobic bacterium, Clostridium botulinum. They are largely used in the clinical practice to treat a number of pathologic conditions characterized by the spasticity of striated muscles. Moreover, the neurotoxin is also used, in an off label setting, in the treatment of pain related disorders, such as chronic pelvic pain. Interstitial cystitis/bladder painful syndrome, category III, nonbacterial chronic prostatitis/chronic pelvic pain syndrome, vaginismus and vulvodynia, are actually fields of application and research of botulinum toxins in the affected patients. Some robust evidences exist on the efficacy and safety of botulinum toxin type A in patients affected by interstitial cystitis/bladder painful syndrome, but no consistent data are available on the use of the neurotoxin in the other pelvic pain conditions. To date, there is the urgent need to have adequate randomized, controlled studies to definitively establish the role of botulinum toxins in treating pelvic pain conditions.

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References

  1. Erbguth FJ, Naumann M. Historical aspects of botulinum toxin: Justinus Kerner (1786–1862) and the ‘sausage poison’. Neurology. 1999;53:1850–3.

    Article  CAS  PubMed  Google Scholar 

  2. Lamanna C, McElroy OE, Eklund HW. The purification and crystallization of clostridium botulinum type A toxin. Science. 1946;103:613–4.

    Article  CAS  PubMed  Google Scholar 

  3. Hill KK, Smith TJ. Genetic diversity within clostridium botulinum serotypes, botulinum neurotoxin gene clusters and toxin subtypes. Curr Top Microbiol Immunol. 2013;364:1–20.

    PubMed  Google Scholar 

  4. Patil S, Willett O, Thompkins T, et al. Botulinum toxin: pharmacology and therapeutic roles in pain states. Curr Pain Headache Rep. 2016;20:1–8.

    Article  Google Scholar 

  5. Zhang S, Masuyer G, Zhang J, et al. Identification and characterization of a novel botulinum neurotoxin. Nat Commun. 2017;8:14,130.

    Article  CAS  Google Scholar 

  6. Lew MF. Review of the FDA-approved uses of botulinum toxins, including data suggesting efficacy in pain reduction. Clin J Pain. 2002;18:142–6.

    Article  Google Scholar 

  7. Lacy DB, Tepp W, Cohen AC, DasGupta BR, Stevens RC. Crystal structure of botulinum neurotoxin type A and implications for toxicity. Nat Struct Biol. 1998;5:898–902.

    Article  CAS  PubMed  Google Scholar 

  8. Dong M, Yeh F, Tepp WH, et al. SV2 is the protein receptor for botulinum neurotoxin A. Science. 2006;312:592–6.

    Article  CAS  PubMed  Google Scholar 

  9. Simpson LL. Molecular pharmacology of botulinum toxin and tetanus toxoid. Annu Rev Pharmacol Toxicol. 1986;26:427–53.

    Article  CAS  PubMed  Google Scholar 

  10. Drachman DB. Botulinum toxin as a tool for research on the nervous system. In: Simpson LL, editor. Neuropoisons. Their physiological actions. New York: Plenum; 1971. p. 325–47.

    Chapter  Google Scholar 

  11. Dover JS, Monheit G, Greener M, et al. Botulinum toxin in aesthetic medicine: myths and realities. Dermatol Surg. 2018;44:249–60.

    Article  CAS  PubMed  Google Scholar 

  12. Rivera Día RC, Lotero MAA, Suarez MVA, et al. Botulinum toxin for the treatment of chronic pain. Review of the evidence. Colomb J Anesthesiol. 2014;42:205–13.

    Google Scholar 

  13. Freund B, Schwartz M. Temporal relationship of muscle weakness and pain reduction in subjects treated with botulinum toxin A. J Pain. 2003;4:159–65.

    Article  CAS  PubMed  Google Scholar 

  14. Antonucci F, Rossi C, Gianfranceschi L, et al. Long-distance retrograde effects of botulinum neurotoxin A. J Neurosci. 2008;28:3689–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Bomba-Warczak E, Vevea JD, Brittain JM, et al. Interneuronal transfer and distal action of tetanus toxin and botulinum neurotoxins A and D in central neurons. Cell Rep. 2016;16:1974–198.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Caleo M, Restani L. Direct central nervous system effects of botulinum neurotoxin. Toxicon. 2018;147:68–72.

    Article  CAS  PubMed  Google Scholar 

  17. Ramachandran R, Lam C, Yaksh TL. Botulinum toxin in migraine: role of transport in trigemino-somatic and trigemino-vascular afferents. Neurobiol Dis. 2015;79:111–22.

    Article  CAS  PubMed  Google Scholar 

  18. Cocco A, Albanese A. Recent developments in clinical trials of bont. Toxicon. 2017;123:77–83.

    Google Scholar 

  19. Marinelli S, Vacca V, Ricordy R, et al. The analgesic effect on neuropathic pain of retrogradely transported botulinum neurotoxin A involves Schwann cells and astrocytes. PLoS One. 2012;7:e47977.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Silva LBD, Poulsen JN, Arendt-Nielsen L, et al. Botulinum neurotoxin type A modulates vesicular release of glutamate from satellite glial cells. J Cell Mol Med. 2015;19:1900–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Matak I, Bach-Rojecky L, Filipović B, et al. Behavioral and immunohistochemical evidence for central antinociceptive activity of botulinum toxin A. Neuroscience. 2011;186:201–7.

    Article  CAS  PubMed  Google Scholar 

  22. Matak I, Tékus V, Bölcskei K, et al. Involvement of substance P in the antinociceptive effect of botulinum toxin type A: evidence from knockout mice. Neuroscience. 2017;358:137–45.

    Article  CAS  PubMed  Google Scholar 

  23. Drinovac V, Bach-Rojecky L, Matak I, et al. Involvement of μ-opioid receptors in antinociceptive action of botulinum toxin type A. Neuropharmacology. 2013;70:331–7.

    Article  CAS  PubMed  Google Scholar 

  24. Zychowska M, Rojewska E, Makuch W, et al. Participation of pro- and anti-nociceptive interleukins in botulinum toxin A-induced analgesia in a rat model of neuropathic pain. Eur J Pharmacol. 2016;791:377–88.

    Article  CAS  PubMed  Google Scholar 

  25. Mika J, Rojewska E, Makuch W, et al. The effect of botulinum neurotoxin A on sciatic nerve injury-induced neuroimmunological changes in rat dorsal root ganglia and spinal cord. Neuroscience. 2011;175:358–66.

    Article  CAS  PubMed  Google Scholar 

  26. Vacca V, Marinelli S, Luvisetto S, et al. Botulinum toxin A increases analgesic effects of morphine, counters development of morphine tolerance and modulates glia activation and μ opioid receptor expression in neuropathic mice. Brain Behav Immun. 2013;32:40–50.

    Article  CAS  PubMed  Google Scholar 

  27. Kim YJ, Kim JH, Lee KJ, et al. Botulinum neurotoxin type A induces TLR2-mediated inflammatory responses in macrophages. PLoS One. 2015;e0120840:10.

    Google Scholar 

  28. Smith CP, Boone TB, de Groat WC. et al. Effect of stimulation intensity and botulinum toxin isoform on rat bladder strip contractions. Brain Res Bull. 2003;61:165–71.

    Article  CAS  PubMed  Google Scholar 

  29. Smith CP, Gangitano DA, Munoz A, et al. Botulinum toxin type A normalizes alterations in urothelial ATP and NO release induced by chronic spinal cord injury. Neurochem Int. 2008;52:1068–75.

    Article  CAS  PubMed  Google Scholar 

  30. Durham PL, Cady R. Regulation of calcitonin gene-related peptide secretion from trigeminal nerve cells by botulinum toxin type A: implications for migraine therapy. Headache. 2004;44:35–42.

    Article  PubMed  Google Scholar 

  31. Welch MJ, Purkiss JR, Foster KA. Sensitivity of embryonic rat dorsal root ganglia neurons to Clostridium botulinum neurotoxins. Toxicon. 2000;38:245–58.

    Article  CAS  PubMed  Google Scholar 

  32. Top T, Sekerci CA, Isbilen-Basok B, et al. The effect of intradetrusor botulinum neurotoxin type A on urinary NGF, TGF BETA-1, TIMP-2 levels in children with neurogenic detrusor overactivity due to myelodysplasia. NeurourolUrodyn. 2017;36:1896–902.

    CAS  Google Scholar 

  33. Chuang YC, Yoshimura N, Huang CC, et al. Intraprostatic botulinum toxin A injection inhibits cyclooxygenase-2 expression and suppresses prostatic pain on capsaicin induced prostatitis model in rat. J Urol. 2008;180:742–8.

    Article  CAS  PubMed  Google Scholar 

  34. Liu HT, Kuo HC. Intravesical botulinum toxin A injections plus hydrodistension can reduce nerve growth factor production and control bladder pain in interstitial cystitis. Urology. 2007;70:463–8.

    Article  PubMed  Google Scholar 

  35. Giannantoni A, Di Stasi SM, Nardicchi V, et al. Botulinum-A toxin injections into the detrusor muscle decrease nerve growth factor bladder tissue levels in patients with neurogenic detrusor overactivity. J Urol. 2006;175:2341–4.

    Article  CAS  PubMed  Google Scholar 

  36. Xiao L, Cheng J, Zhuang Y, et al. Botulinum toxin type A reduces hyperalgesia and TRPV1 expression in rats with neuropathic pain. Pain Med. 2013;14:276–86.

    Article  PubMed  Google Scholar 

  37. Smith CP, Radziszewski P, Borkowski A, et al. Botulinum toxin A has antinociceptive effects in treating interstitial cystitis. Urology. 2004;64:871–5.

    Article  PubMed  Google Scholar 

  38. Apostolidis A, Popat R, Yiangou Y, et al. Decreased sensory receptors P2X3 and TRPV1 in suburothelial nerve fibers following intradetrusor injections of botulinum toxin for human detrusor overactivity. J Urol. 2005;174:977–82.

    Article  CAS  PubMed  Google Scholar 

  39. Giannantoni A, Costantini E, Di Stasi SM, et al. Botulinum A toxin intravesical injections in the treatment of painful bladder syndrome: a pilot study. Eur Urol. 2006;49:704–9.

    Article  CAS  PubMed  Google Scholar 

  40. Ramsay AK, Small DR, Conn IG. Intravesical botulinum toxin type A in chronic interstitial cystitis: results of a pilot study. Surgeon. 2007;5:331–3.

    Article  CAS  PubMed  Google Scholar 

  41. Giannantoni A, Porena M, Costantini E, et al. Botulinum A toxin intravesical injection in patients with painful bladder syndrome: 1-Year followup. J Urol. 2008;179:1031–4.

    Article  CAS  PubMed  Google Scholar 

  42. Giannantoni A, Cagini R, Del Zingaro M, et al. Botulinum A toxin intravesical injections for painful bladder syndrome: impact upon pain, psychological functioning and Quality of Life. Curr Drug Deliv. 2010;7:442–6.

    Article  CAS  PubMed  Google Scholar 

  43. Chung SD, Kuo YC, Kuo HC. Intravesical onabotulinumtoxinA injections for refractory painful bladder syndrome. Pain Physician. 2012;15:197–202.

    PubMed  Google Scholar 

  44. Kuo HC, Chancellor MB. Comparison of intravesical botulinum toxin type A injections plus hydrodistention with hydrodistention alone for the treatment of refractory interstitial cystitis/painful bladder syndrome. BJU Int. 2009;104:657–61.

    Article  CAS  PubMed  Google Scholar 

  45. Akiyama Y, Nomiya A, Niimi A, et al. Botulinum toxin type A injection for refractory interstitial cystitis: A randomized comparative study and predictors of treatment response. Int J Urol. 2015;22:835–8.

    Article  CAS  PubMed  Google Scholar 

  46. Kuo HC, Jiang YH, Tsai YC, et al. Intravesical botulinum toxin-A injections reduce bladder pain of interstitial cystitis/bladder pain syndrome refractory to conventional treatment—a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial. NeurourolUrodyn. 2016;35:609–14.

    CAS  Google Scholar 

  47. Pinto RA, Costa D, Morgado A, et al. Intratrigonal onabotulinumtoxinA improves bladder symptoms and quality of life in patients with bladder pain syndrome/interstitial cystitis: a pilot, single center, randomized, double-blind, placebo controlled trial. J Urol. 2018;199:998–1003.

    Article  CAS  PubMed  Google Scholar 

  48. Tyagi P, Kashyap M, Yoshimura N, et al. Past, present and future of chemodenervation with botulinum toxin in the treatment of overactive bladder. J Urol. 2017;197:982–90.

    Article  CAS  PubMed  Google Scholar 

  49. Petrou SP, Parker AS, Crook JE, et al. Botulinum A toxin/dimethyl sulfoxide bladder instillations for women with refractory idiopathic detrusor overactivity: a phase 1/2 study. Mayo Clin Proc. 2009;84:702–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Khera M, Somogyi GT, Salas NA, et al. In vivo effects of botulinum toxin A on visceral sensory function in chronic spinal cord-injured rats. Urology. 2005;66:208–12.

    Article  PubMed  Google Scholar 

  51. Chuang YC, Kaufmann JH, Chancellor DD, et al. Bladder instillation of liposome encapsulated onabotulinumtoxinA improves overactive bladder symptoms: a prospective, multicenter, double-blind, randomized trial. J Urol. 2014;192:1743–9.

    Article  CAS  PubMed  Google Scholar 

  52. Lin T, Zhang Y, Wu J, et al. A floating hydrogel system capable of generating CO2 bubbles to diminish urinary obstruction after intravesical instillation. Pharm Res. 2014;31:2655–63.

    Article  CAS  PubMed  Google Scholar 

  53. Rappaport YH, Zisman A, Jeshurun-Gutshtat M, et al. Safety and feasibility of intravesical instillation of botulinum toxin-A in hydrogel-based slow-release delivery system in patients with interstitial cystitis-bladder pain syndrome: a pilot study. Urology. 2018;114:60–5.

    Article  PubMed  Google Scholar 

  54. Pontari MA. Chronic prostatitis/chronic pelvic pain syndrome and interstitial cystitis: are they related? Curr Urol Rep. 2006;7:329–34.

    Article  PubMed  Google Scholar 

  55. Abdel-Meguid TA, Mosli HA, Farsi H, et al. Treatment of refractory category III nonbacterial chronic prostatitis/chronic pelvic pain syndrome with intraprostatic injection of onabotulinumtoxinA: a prospective controlled study. Can J Urol. 2018;25:9273–80.

    PubMed  Google Scholar 

  56. El-Enen MA, Abou-Farha M, El-Abd A, et al. Intraprostatic injection of botulinum toxin-A in patients with refractory chronic pelvic pain syndrome: the transurethral vs. transrectal approach. Arab J Urol. 2015;13:94–9.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Falahatkar A, Shahab E, Moghaddam KG, et al. Transurethral intraprostatic injection of botulinum neurotoxin type A for the treatment of chronic prostatitis/chronic pelvic pain syndrome: results of a prospective pilot double-blind and randomized placebo-controlled study. BJU Int. 2015;116:641–9.

    Article  CAS  PubMed  Google Scholar 

  58. Gottsch HP, Yang CC, Berger RE. A pilot study of botulinum toxin A for male chronic pelvic pain syndrome. Scand J Urol Nephrol. 2011;45:72–6.

    Article  CAS  PubMed  Google Scholar 

  59. Jarvis SKSK, Abbott JA, Lenart MB, et al. 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;44:46–50.

    Article  PubMed  Google Scholar 

  60. Bertolasi LL, Frasson E, Cappelletti JY, et al. Botulinum neurotoxin type A injections for vaginismus secondary to vulvar vestibulitis syndrome. Obstet Gynecol. 2009;114:1008–16.

    Article  CAS  PubMed  Google Scholar 

  61. Abbott JAJA, Jarvis SK, Lyons SD, et al. Botulinum toxin type A for chronic pain and pelvic floor spasm in women: a randomized controlled trial. Obstet Gynecol. 2006;108:915–23.

    Article  PubMed  Google Scholar 

  62. Petersen CD, Giraldi A, Lundvall EK. Botulinum toxin type A-a novel treatment for provoked vestibulodynia? Results from a randomized, placebo controlled, double blinded study. J Sex Med. 2009;6:2523–37.

    Article  CAS  PubMed  Google Scholar 

  63. Hedebo Hansen T, Guldberg R, Meinert M. Botulinum toxin-treatment of localized provoked vulvodynia refractory to conventional treatment. Eur J Obstet Gynecol Reprod Biol. 2019;234:6–9.

    Article  CAS  PubMed  Google Scholar 

  64. Dolly JO, O’Connell MA. Neurotherapeutics to inhibit exocytosis from sensory neurons for the control of chronic pain. Curr Opin Pharmacol. 2012;12:100–8.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medical and Surgical Sciences and Neurosciences, Functional and Surgical Urology Unit, University of Siena, Siena, Italy

    Antonella Giannantoni

  2. Department of Urology, San Donato Hospital, Arezzo, Italy

    Marilena Gubbiotti

  3. Serafico Institute, Research Center “InVita”, Assisi, Italy

    Marilena Gubbiotti

Authors
  1. Antonella Giannantoni
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  2. Marilena Gubbiotti
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Correspondence to Antonella Giannantoni .

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Editors and Affiliations

  1. Neuro-Urology Department, CTO-Spinal Unit Hospital, Citta' Della Salute e della Scienza, Turin, Italy

    Alessandro Giammò

  2. Autonomic Dysfunctions Center - Rehabilitation Unit, S. Giovanni Bosco Hospital - ASL Città di Torino, Turin, Italy

    Antonella Biroli

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Giannantoni, A., Gubbiotti, M. (2021). Botulinum Toxin in Chronic Pelvic Pain Management. In: Giammò, A., Biroli, A. (eds) Chronic Pelvic Pain and Pelvic Dysfunctions. Urodynamics, Neurourology and Pelvic Floor Dysfunctions. Springer, Cham. https://doi.org/10.1007/978-3-030-56387-5_17

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  • DOI: https://doi.org/10.1007/978-3-030-56387-5_17

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