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Nervenheilkunde 2017; 36(05): 315-323
DOI: 10.1055/s-0038-1627027
Schmerz
Schattauer GmbH

Botulinumtoxin zur Behandlung von neuropathischen Schmerzen

Botulinum toxin for treatment of neuropathic pain
C. Sommer
1   Neurologische Klinik, Universitätsklinikum Würzburg
,
N. Üçeyler
1   Neurologische Klinik, Universitätsklinikum Würzburg
› Institutsangaben
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Publikationsverlauf

eingegangen am: 05. November 2016

angenommen am: 20. November 2016

Publikationsdatum:
20. Januar 2018 (online)

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Zusammenfassung

Die Behandlung neuropathischer Schmerzen mit systemisch wirksamen oral verabreichten Pharmaka ist bei vielen Patienten wirksam, kann jedoch zu zentralnervösen unerwünschten Wirkungen wie Müdigkeit oder Schwindel führen. Daher sind in den letzten Jahren topische Therapien in das Zentrum der Aufmerksamkeit gerückt. Botulinumtoxin, etabliert in der Therapie von Dystonien und Spastik, wurde zunehmend bei Schmerzerkrankungen getestet, hierbei ist Botulinum-Neurotoxin A der am besten untersuchte Serotyp. Die häufigsten Indikationen waren Schmerzen im Trigeminusversorgungsbereich und periphere neuropathische Schmerzen. Bei den meisten Studien war Botulinum-Neurotoxin A Placebo deutlich überlegen. Präklinische Studien zum Wirkmechanismus erbrachten die Erkenntnis, dass neben dem erwarteten peripheren Effekt sehr wahrscheinlich auch eine zentrale Reduktion der Ausschüttung von exzitatorischen Neurotransmittern an der Wirkung beteiligt ist.

Summary

Treatment of neuropathic pain with orally administered systemically acting drugs is effective in many patients, but can lead to side effects in the central nervous system such as fatigue or dizziness. Therefore, topical therapies have been the focus of attention in recent years. Botulinum toxin, established in the treatment of dystonia and spasticity, has been increasingly tested in recent years for painful diseases. Botulinum neurotoxin A was most often studied. The most common indications were pain in the trigeminal area and peripheral neuropathic pain. In most studies, botulinum neurotoxin A was significantly superior to placebo. Preclinical studies on the mechanism of action have shown that besides the expected peripheral effect, a central reduction of the excretion of excitatory neurotransmitters is most likely involved in the effect.

Schlüsselwörter

Neuropathischer Schmerz - Botulinumtoxin - Therapie

Keywords

Neuropathic pain - Botulinum toxin - therapy
 

  • Literatur

  • 1 Matak I, Lackovic Z. Botulinum toxin A, brain and pain. Prog Neurobiol 2014; 119–120: 39-59.
    PubMedGoogle Scholar
  • 2 Pellett S, Yaksh TL, Ramachandran R. Current status and future directions of botulinum neurotoxins for targeting pain processing. Toxins 2015; 07: 4519-63.
    CrossrefPubMedGoogle Scholar
  • 3 Cui M, Khanijou S, Rubino J, Aoki KR. Subcutaneous administration of botulinum toxin A reduces formalin-induced pain. Pain 2004; 107: 125-33.
    CrossrefPubMedGoogle Scholar
  • 4 Vacca V, Marinelli S, Eleuteri C, Luvisetto S, Pavone F. Botulinum neurotoxin A enhances the analgesic effects on inflammatory pain and antagonizes tolerance induced by morphine in mice. Brain Behav Immun 2012; 26: 489-99.
    CrossrefPubMedGoogle Scholar
  • 5 Lee WH, Shin TJ, Kim HJ, Lee JK, Suh HW, Lee SC. et al. Intrathecal administration of botulinum neurotoxin type A attenuates formalin-induced nociceptive responses in mice. Anesth Analg 2011; 112: 228-35.
    CrossrefPubMedGoogle Scholar
  • 6 Luvisetto S, Marinelli S, Lucchetti F, Marchi F, Cobianchi S, Rossetto O. et al. Botulinum neurotoxins and formalin-induced pain: central vs. peripheral effects in mice. Brain Res 2006; 1082: 124-31.
    CrossrefPubMedGoogle Scholar
  • 7 Kim HJ, Lee GW, Kim MJ, Yang KY, Kim ST, Bae YC. et al. Antinociceptive effects of transcytosed botulinum neurotoxin type A on trigeminal nociception in rats. Korean J Physiol Pharmacol 2015; 19: 349-55.
    CrossrefPubMedGoogle Scholar
  • 8 Matak I, Stracenski I, Lackovic Z. Comparison of analgesic effects of single versus repeated injection of botulinum toxin in orofacial formalin test in rats. J Neural Transm 2013; 120: 141-4.
    CrossrefPubMedGoogle Scholar
  • 9 Bach-Rojecky L, Lackovic Z. Antinociceptive effect of botulinum toxin type a in rat model of carrageenan and capsaicin induced pain. Croat Med J 2005; 46: 201-8.
    PubMedGoogle Scholar
  • 10 Favre-Guilmard C, Auguet M, Chabrier PE. Different antinociceptive effects of botulinum toxin type A in inflammatory and peripheral polyneuropathic rat models. Eur J Pharmacol 2009; 617: 48-53.
    CrossrefPubMedGoogle Scholar
  • 11 Shin MC, Yukihira T, Ito Y, Akaike N. Antinociceptive effects of A1 and A2 type botulinum toxins on carrageenan-induced hyperalgesia in rat. Toxicon 2013; 64: 12-9.
    CrossrefPubMedGoogle Scholar
  • 12 Drinovac VVlah, Bach-Rojecky L, Lackovic Z. Antinociceptive action of botulinum toxin type A in carrageenan-induced mirror pain. J Neural Transm. 2016 epub..
    PubMedGoogle Scholar
  • 13 Luvisetto S, Vacca V, Cianchetti C. Analgesic effects of botulinum neurotoxin type A in a model of allyl isothiocyanate- and capsaicin-induced pain in mice. Toxicon 2015; 94: 23-8.
    CrossrefPubMedGoogle Scholar
  • 14 Krug HE, Frizelle S, McGarraugh P, Mahowald ML. Pain behavior measures to quantitate joint pain and response to neurotoxin treatment in murine models of arthritis. Pain Med 2009; 10: 1218-28.
    CrossrefPubMedGoogle Scholar
  • 15 Drinovac V, Bach-Rojecky L, Matak I, Lackovic Z. Involvement of mu-opioid receptors in antinociceptive action of botulinum toxin type A. Neuropharmacology 2013; 70: 331-7.
    CrossrefPubMedGoogle Scholar
  • 16 Bach-Rojecky L, Relja M, Lackovic Z. Botulinum toxin type A in experimental neuropathic pain. J Neural Transm 2005; 112: 215-9.
    CrossrefPubMedGoogle Scholar
  • 17 Park HJ, Lee Y, Lee J, Park C, Moon DE. The effects of botulinum toxin A on mechanical and cold allodynia in a rat model of neuropathic pain. Can J Anaesth 2006; 53: 470-7.
    CrossrefPubMedGoogle Scholar
  • 18 Xiao L, Cheng J, Zhuang Y, Qu W, Muir J, Liang H. et al. Botulinum toxin type A reduces hyperalgesia and TRPV1 expression in rats with neuropathic pain. Pain Med 2013; 14: 276-86.
    CrossrefPubMedGoogle Scholar
  • 19 Xiao L, Cheng J, Dai J, Zhang D. Botulinum toxin decreases hyperalgesia and inhibits P2X3 receptor over-expression in sensory neurons induced by ventral root transection in rats. Pain Med 2011; 12: 1385-94.
    CrossrefPubMedGoogle Scholar
  • 20 Marinelli S, Vacca V, Ricordy R, Uggenti C, Tata AM, Luvisetto S. et al. The analgesic effect on neuropathic pain of retrogradely transported botulinum neurotoxin A involves Schwann cells and astrocytes. PLoS One 2012; 07: e47977.
    CrossrefPubMedGoogle Scholar
  • 21 Luvisetto S, Marinelli S, Cobianchi S, Pavone F. Anti-allodynic efficacy of botulinum neurotoxin A in a model of neuropathic pain. Neuroscience 2007; 145: 1-4.
    CrossrefPubMedGoogle Scholar
  • 22 Mika J, Rojewska E, Makuch W, Korostynski M, Luvisetto S, Marinelli S. 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.
    CrossrefPubMedGoogle Scholar
  • 23 Filipovic B, Matak I, Bach-Rojecky L, Lackovic Z. Central action of peripherally applied botulinum toxin type A on pain and dural protein extravasation in rat model of trigeminal neuropathy. PLoS One 2012; 07: e29803.
    CrossrefPubMedGoogle Scholar
  • 24 Kitamura Y, Matsuka Y, Spigelman I, Ishihara Y, Yamamoto Y, Sonoyama W. et al. Botulinum toxin type a (150 kDa) decreases exaggerated neurotransmitter release from trigeminal ganglion neurons and relieves neuropathy behaviors induced by infraorbital nerve constriction. Neuro- science 2009; 159: 1422-9.
    Google Scholar
  • 25 Kumada A, Matsuka Y, Spigelman I, Maruhama K, Yamamoto Y, Neubert JK. et al. Intradermal injection of Botulinum toxin type A alleviates infraorbital nerve constriction-induced thermal hyperalgesia in an operant assay. J Oral Rehabil 2012; 39: 63-72.
    CrossrefPubMedGoogle Scholar
  • 26 Bach-Rojecky L, Salkovic-Petrisic M, Lackovic Z. Botulinum toxin type A reduces pain supersensitivity in experimental diabetic neuropathy: bilateral effect after unilateral injection. Eur J Pharmacol 2010; 633: 10-4.
    CrossrefPubMedGoogle Scholar
  • 27 Ma L, Nagai J, Sekino Y, Goto Y, Nakahira S, Ueda H. Single application of A2 NTX, a botulinum toxin A2 subunit, prevents chronic pain over long periods in both diabetic and spinal cord injury-induced neuropathic pain models. J Pharmacol Sci 2012; 119: 282-6.
    CrossrefPubMedGoogle Scholar
  • 28 Park HJ, Marino MJ, Rondon ES, Xu Q, Yaksh TL. The effects of intraplantar and intrathecal botulinum toxin type B on tactile allodynia in mono and polyneuropathy in the mouse. Anesth Analg 2015; 121: 229-38.
    CrossrefPubMedGoogle Scholar
  • 29 Chuang YC, Yoshimura N, Huang CC, Chiang PH, Chancellor MB. Intravesical botulinum toxin a administration produces analgesia against acetic acid induced bladder pain responses in rats. J Urol 2004; 172: 1529-32.
    CrossrefPubMedGoogle Scholar
  • 30 Chuang YC, Yoshimura N, Huang CC, Wu M, Chiang PH, Chancellor MB. 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.
    CrossrefPubMedGoogle Scholar
  • 31 Drinovac V, Bach-Rojecky L, Babic A, Lackovic Z. Antinociceptive effect of botulinum toxin type A on experimental abdominal pain. Eur J Pharmacol 2014; 745: 190-5.
    CrossrefPubMedGoogle Scholar
  • 32 Coelho A, Oliveira R, Rossetto O, Cruz CD, Cruz F, Avelino A. Intrathecal administration of botulinum toxin type A improves urinary bladder function and reduces pain in rats with cystitis. Eur J Pain 2014; 18: 1480-9.
    CrossrefPubMedGoogle Scholar
  • 33 Bach-Rojecky L, Lackovic Z. Central origin of the antinociceptive action of botulinum toxin type A. Pharmacol Biochem Behav 2009; 94: 234-8.
    CrossrefPubMedGoogle Scholar
  • 34 Matak I, Bach-Rojecky L, Filipovic B, Lackovic Z. Behavioral and immunohistochemical evidence for central antinociceptive activity of botulinum toxin A. Neuroscience 2011; 186: 201-7.
    CrossrefPubMedGoogle Scholar
  • 35 Wu C, Xie N, Lian Y, Xu H, Chen C, Zheng Y. et al. Central antinociceptive activity of peripherally applied botulinum toxin type A in lab rat model of trigeminal neuralgia. Springerplus 2016; 05: 431.
    CrossrefPubMedGoogle Scholar
  • 36 Matak I, Riederer P, Lackovic Z. Botulinum toxin’s axonal transport from periphery to the spinal cord. Neurochem Int 2012; 61: 236-9.
    CrossrefPubMedGoogle Scholar
  • 37 Shackleton T, Ram S, Black M, Ryder J, Clark GT, Enciso R. 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.
    CrossrefPubMedGoogle Scholar
  • 38 Apalla Z, Sotiriou E, Lallas A, Lazaridou E, Ioannides D. Botulinum toxin A in postherpetic neuralgia: a parallel, randomized, double-blind, single-dose, placebo-controlled trial. Clin J Pain 2013; 29: 857-64.
    CrossrefPubMedGoogle Scholar
  • 39 Xiao L, Mackey S, Hui H, Xong D, Zhang Q, Zhang D. Subcutaneous injection of botulinum toxin a is beneficial in postherpetic neuralgia. Pain Med 2010; 11: 1827-33.
    CrossrefPubMedGoogle Scholar
  • 40 Morra ME, Elgebaly A, Elmaraezy A, Khalil AM, Altibi AM, Vu TL. et al. Therapeutic efficacy and safety of botulinum toxin A therapy in trigeminal neuralgia: a systematic review and meta-analysis of randomized controlled trials. J Headache Pain 2016; 17: 63.
    CrossrefPubMedGoogle Scholar
  • 41 Oh HM, Chung ME. Botulinum toxin for neuropathic pain: A review of the literature. Toxins 2015; 07: 3127-54.
    CrossrefPubMedGoogle Scholar
  • 42 Ranoux D, Attal N, Morain F, Bouhassira D. Botulinum toxin type A induces direct analgesic effects in chronic neuropathic pain. Ann Neurol 2008; 64: 274-83.
    CrossrefPubMedGoogle Scholar
  • 43 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: 1473-8.
    CrossrefPubMedGoogle Scholar
  • 44 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: 106-11.
    PubMedGoogle Scholar
  • 45 Breuer B, Sperber K, Wallenstein S, Kiprovski K, Calapa A, Snow B. et al. Clinically significant placebo analgesic response in a pilot trial of botulinum B in patients with hand pain and carpal tunnel syndrome. Pain Med 2006; 07: 16-24.
    CrossrefPubMedGoogle Scholar
  • 46 Safarpour D, Salardini A, Richardson D, Jabbari B. Botulinum toxin A for treatment of allodynia of complex regional pain syndrome: a pilot study. Pain Med 2010; 11: 1411-4.
    CrossrefPubMedGoogle Scholar
  • 47 Carroll I, Clark JD, Mackey S. Sympathetic block with botulinum toxin to treat complex regional pain syndrome. Ann Neurol 2009; 65: 348-51.
    CrossrefPubMedGoogle Scholar
  • 48 Wu H, Sultana R, Taylor KB, Szabo A. A prospective randomized double-blinded pilot study to examine the effect of botulinum toxin type A injection versus Lidocaine/Depomedrol injection on residual and phantom limb pain: initial report. Clin J Pain 2012; 28: 108-12.
    CrossrefPubMedGoogle Scholar
  • 49 Attal N, de Andrade DC, Adam F, Ranoux D, Teixeira MJ, Galhardoni R. 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.
    CrossrefPubMedGoogle Scholar
  • 50 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: 569-78.
    CrossrefPubMedGoogle Scholar