Aktuelle Neurologie 2002; 29(8): 389-401
DOI: 10.1055/s-2002-34965
Übersicht
© Georg Thieme Verlag Stuttgart · New York

Botulinumtoxin in der Schmerztherapie

Botulinum Toxine in the Treatment of PainT.  Probst1 , D.  Dressler1 , R.  Benecke1 , E.  Kunesch1
  • 1Neurologische Klinik und Poliklinik der Universität Rostock
Further Information

Publication History

Publication Date:
23 October 2002 (online)

Zusammenfassung

Botulinumtoxin (BTX) wird seit mehr als 20 Jahren erfolgreich bei Erkrankungen mit muskulären Hyperaktivitäten eingesetzt. In den letzten Jahren kam es zu einer deutlichen Ausweitung der Anwendung bei autonomen Erkrankungen und in der Schmerztherapie. Die analgetischen Wirkungen von BTX-Injektionen werden vor dem Hintergrund erheblicher Plazeboeffekte und teilweise methodischer Mängel der vorgelegten Studien kontrovers diskutiert. Weiterhin bestehen noch unzureichende Konzepte zur Schmerzphysiologie allgemein sowie zu den spezifischen analgetischen Wirkmechanismen von Botulinumtoxin. Neben der Schmerzreduktion durch die bekannte BTX-Wirkung an der neuromuskulären Endplatte werden weitere lokale schmerzreduzierende Mechanismen und Wirkungen an anderen synaptischen Systemen postuliert. Derzeit kann BTX zur Schmerztherapie bei Dystonien und Spastiksyndromen sowie bei Analfissuren und Achalasie empfohlen werden. Bei myofaszialen Schmerzen, Migräne, Kopfschmerzen vom Spannungstyp und anderen seltenen Kopfschmerzsyndromen wurde eine Schmerzreduktion durch BTX berichtet, aber der definitive Beleg nach Kriterien der evidenzbasierten Medizin steht noch aus. Bei Fibromyalgie scheint keine sichere klinische Wirkung vorzuliegen. Es ist zu erwarten, dass in Zukunft die Bedeutung von BTX in der Schmerztherapie zunehmen wird.

Abstract

Botulinum toxin (BTX) has been used for more than 20 years to treat various muscle hyperactivity syndromes. Over the past years its use has expanded into the treatment of autonomic disorders and pain. Analgesic effects of BTX have been discussed controversially due to substantial placebo effects and flaws of the study designs used. Additionally, pathophysiological concepts of pain as well as specific analgesic mechanisms of BTX remain largely unclear. Apart from a pain reduction through the well documented BTX effects at the neuromuscular endplate, additional analgesic mechanisms including other synaptic and local effects have been suggested. Currently, BTX can be recommended for pain treatment in dystonia and spasticity as well as in analfissures and achalasia. In myofascial pain syndromes, migraine, tension-type headache and other rare headache syndromes pain relief by BTX has been reported, but definite proof according to evidence based medicine criteria is still lacking. In fibromyalgia there seems to be no analgesic effect. The role of BTX in pain therapy is likely to increase in the future.

Literatur

  • 1 Scott A B. Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery.  J Pediadr Ophthalmol Strabismus. 1980;  17 21-25
  • 2 Aoki K. Pharmacology and immunology of botulinum toxin serotypes.  J Neurol. 2001;  248 (Suppl 1) 3-10
  • 3 Dressler D. Botulinum Toxin Therapy. Stuttgart, New York; Thieme 2000
  • 4 Jost W, Kohl A. Botulinum toxin: evidence-based medicine criteria in rare indications.  J Neurol. 2001;  248 (Suppl 1) 39-44
  • 5 Brin M F, Fahn S, Moskowitz C. et al . Localized injections of botulinum toxin for the treatment of focal dystonia and hemifacial spasm.  Adv Neurol. 1988;  50 599-608
  • 6 Brin M F, Lew M, Adler C. et al . Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-resistant cervical dystonia.  Neurology. 1999;  53 1431-1438
  • 7 Hilker R, Schischniaschvili M, Ghaemi M. et al . Health related quality of life is improved by botulinum neurotoxin type A in long term treated patients with focal dystonia.  J Neurol Neurosurg Psychiatry. 2001;  71 193-199
  • 8 Kelm S, Gerats G, Chalkiadaki A, Hefter H. Reduction of pain and muscle spasms by botulinum toxin A.  Nervenarzt. 2001;  72 302-306
  • 9 Lew M F, Adornato B T, Duane D D. et al . Botulinum toxin type B: A double-blind, placebo-controlled, safety and efficacy study in cervical dystonia.  Neurology. 1997;  49 701-707
  • 10 Poewe W, Deuschl G, Nebe A. et al . What is the optimal dose of botulinum toxin A in the treatment of cervical dystonia? Results of a double blind, placebo controlled dose ranging study using dysport.  J Neurol Neurosurg Psychiatry. 1998;  64 13-17
  • 11 Tarsy D, First E R. Painful cervical dystonia: clinical features and response to treatment with botulinum toxin.  Mov Disord. 1999;  14 1043-1045
  • 12 Chalkiadaki A, Rohr U P, Hefter H. Frühe Schmerzreduktion in der Therapie von Spastik nach einmaliger Botulinustoxin-A-Injektion.  Dtsch Med Wochenschr. 2001;  126 1361-1364
  • 13 Carruthers J, Carruthers A. Treatment of glabellar frown lines with C. botulinum-A exotoxin.  J Dermatol Surg Oncol. 1992;  18 17-21
  • 14 Carruthers A, Langtry J A, Carruthers J, Robinson G. Improvement of tension-type headache when treating wrinkles with botulinum toxin A injections.  Headache. 1999;  39 662-665
  • 15 Krack P, Hornig C, Dorndorf W. Resolution of chronic tension-type headache after botulinum toxin treatment of idiopathic blepharospasm.  Mov Disord. 1995;  10 388
  • 16 Mense S. Neurobiologische Grundlagen von Muskelschmerz.  Schmerz. 1999;  13 3-17
  • 17 Simons D G, Mense S. Understanding and measurement of muscle tone as related to clinical muscle pain.  Pain. 1998;  75 1-17
  • 18 Porta M, Perretti A, Gamba M, Luccarelli G, Fornari M. The rationale and results of treating muscle spasm and myofascial syndromes with botulinum toxin type A.  Pain Digest. 1998;  8 346-352
  • 19 Cui M L, Khanijou S, Rubino J, Aoki K R. Botulinum toxin A inhibits the inflammatory pain in the rat formalin model. New Orleans; Society for Neuroscience Annual Meeting 2000 Poster 246.2
  • 20 Dolly J, Ashton A, Evans D. et al .Molecular action of botulinum neurotoxins: role of acceptors in targetting to cholinergic nerves and in the inhibition of the release of several transmitters. In: Dowdall M, Hawthorne J (eds) Cellular and molecular basis of cholinergic function. Chichester; Ellis Horwood 1987: 517-535
  • 21 Puffer E, Lomneth R, Sarkar H, Singh B. Differential roles of developmentally distinct SNAP-25 isoforms in the neurotransmitter release process.  Biochemistry. 2001;  40 9374-9378
  • 22 Sala C, Adreose J, Fumagalli G. et al . Calcitonin gene-related peptide: possible role in formation and maintenance of neuromuscular junctions.  J Neurosci. 1995;  15 520-528
  • 23 Suzuki N, Hardebo J E, Kahrstrom J. et al . Neuropeptide Y co-exists with vasoactive intestinal polypeptide and acetylcholine in parasympathetic cerebrovascular nerves originating in the sphenopalatine, otic and internal carotid ganglia of the rat.  Neuroscience. 1990;  36 507-519
  • 24 Welch M, Purkiss J, Foster K. Sensitivity of embryonic rat dorsal root ganglia neurons to Clostridium botulinum neurotoxins.  Toxicon. 2000;  38 245-258
  • 25 Ferrari M. Migraine.  Lancet. 1998;  351 1043-1051
  • 26 Binder W J, Brin M F, Blitzer A. et al . Botulinum toxin type A (BOTOX) for treatment of migraine headaches: an open-label study.  Otolaryngol Head Neck Surg. 2000;  123 669-676
  • 27 Aoki K, Weber J, Patten P. et al .United States Patent Number 6 113 915,. Sep. 5, 2000
  • 28 Wiegand H, Erdmann G, Wellhöner H H. 125 I-labelled botulinum A neurotoxin: pharmacokinetics in cats after intramuscular injection.  Naunyn Schmiedeberg's Arch Pharmacol. 1976;  292 161-165
  • 29 Hagenah R, Benecke R, Wiegand H. Effects of type A Botulinum toxin on the cholinergic transmission at spinal Renshaw cells and on the inhibitory action at Ia inhibitory interneurones.  Naunyn Schmiedeberg's Arch Pharmacol. 1977;  299 267-272
  • 30 Filippi G M, Errico P, Santarelli R. et al . Botulinum A toxin effects on rat jaw muscle spindles.  Acta Otolaryngol. 1993;  113 400-404
  • 31 Rosales R L, Arimura K, Ikenaga S, Osame M. Extrafusal and intrafusal muscle effects in experimental botulinum toxin A injection.  Muscle Nerve. 1996;  19 488-496
  • 32 Guyer B M. Mechanism of botulinum toxin in the relief of chronic pain.  Curr Rev Pain. 1999;  3 427-431
  • 33 Humm A, Pabst C, Lauterburg T, Burgunder J. Enkephalin and aFGF are differentially regulated in rat spinal motoneurons after chemodenervation with botulinum toxin.  Exp Neurol. 2000;  161 361-372
  • 34 Priori A, Berardelli A, Mercuri B, Manfredi M. Physiological effects produced by botulinum toxin treatment of upper limb dystonia. Changes in reciprocal inhibition between forearm muscles.  Brain. 1995;  118 801-807
  • 35 Ärztliche Zentralstelle für Qualitätssicherung .Leitlinien-Info. ÄZQ-Schriftenreihe, Band 1. München; Zuckerschwerdt 1999: 62-68
  • 36 Scottish intercollegiate guidelines network .SIGN Guidelines - An introduction to SIGN Methodology for the development of evidence-based clinical guidelines. Edinburgh; SIGN Publication Number 39. SIGN Secretariat. Royal College of Physicians 1999
  • 37 Chan J, Brin M, Fahn S. Idiopathic cervical dystonia: clinical characteristics.  Mov Disord. 1991;  6 119-126
  • 38 Lindeboom R, Brans J, Aramideh M. et al . Treatment of cervical dystonia: A comparison of outcome measures for outcome assessment.  Mov Disord. 1998;  13 706-712
  • 39 Pal P K, Samii A, Schulzer M. et al . Head tremor in cervical dystonia.  Can J Neurol Sci. 2000;  27 137-142
  • 40 Behari M. Botulinum toxin in the treatment of writer's cramp.  J Assoc Physicians India. 1999;  47 694-698
  • 41 Kunig G, Pogarell O, Oertel W H. Facial pain in a case of cranial dystonia: a case report.  Cephalagia. 1998;  18 709-711
  • 42 Comella C, Shannon K, Jaglin J. Extensor truncal dystonia: Successful treatment with botulinum toxin injections.  Mov Disord. 1998;  13 552-555
  • 43 Cordiviari C, Misra V, Catania S, Lees A. Treatment of dystonic clenched fist with botulinum toxin.  Mov Disord. 2001;  16 907-913
  • 44 Pacchetti C, Albani G, Martignoni E. et al . „Off” painful dystonia in Parkinson's disease treated with botulinum toxin.  Mov Disord. 1995;  10 333-336
  • 45 Dressler D, Argyrakis A, Schönle P W. et al . Botulinumtoxintherapie in der Rehabilitationsneurologie.  Nervenarzt. 1996;  67 686-694
  • 46 Reichel G. Botulinum toxin for treatment of spasticity in adults.  J Neurol. 2001;  248 (Suppl 1) 25-27
  • 47 Benecke R. Botulinum toxin treatment in spasticity of lower extremities. In: Jankovic J, Hallet M (eds) Therapy with Botulinum Toxin. New York; Marcel Dekker 1994: 463-473
  • 48 Bhakta B, Cozens J A, Bamford J M, Chamberlain M A. Use of botulinum toxin in stroke patients with severe upper limb spasticity.  J Neurol Neurosurg Psychiatry. 1996;  61 30-35
  • 49 Dunne J W, Heye N, Dunne S L. Treatment of chronic limb spasticity with botulinum toxin.  J Neurol Neurosurg Psychiatry. 1995;  58 232-235
  • 50 Pierson S H, Katz D I, Tarsy D. Botulinum toxin A in the treatment of spasticity: functional implications and patient selection.  Arch Phys Med Rehabil. 1996;  77 717-721
  • 51 Wissel J, Muller J, Dressnandt J. et al . Management of spasticity associated pain with botulinum toxin A.  J Pain Symptom Manage. 2000;  20 44-49
  • 52 Barwood S, Baillieu C, Boyd R. et al . Analgesic effects of botulinum toxin A: a randomized, placebo-controlled clinical trial.  Dev Med Child Neurol. 2000;  42 116-121
  • 53 Grazko M A, Polo K B, Jabbari B. Botulinum toxin A for spasticity, muscle spasms, and rigidity.  Neurology. 1995;  45 712-717
  • 54 Bakheit A M, Pittstock S, Moore A P. et al . A randomized, double-blind, placebo-controlled study of the efficacy and safety of botulinum toxin type A in upper limb spasticity in patients with stroke.  Eur J Neurol. 2001;  8 559-565
  • 55 Bhakta B, Cozens J A, Chamberlain M A, Bamford J M. Impact of botulinum toxin type A on disability and carer burden due to arm spasticity after stroke: a randomized double-blind placebo controlled trial.  J Neurol Neurosurg Psychiatry. 2000;  69 217-221
  • 56 Hyman N, Barnes M, Bhakta B. et al . Botulinum toxin (Dysport®) treatment of hip adductor spasticity in multiple sclerosis: a prospective, randomised, double-blind, placebo-controlled, dose ranging study.  J Neurol Neurosurg Psychiatry. 2000;  68 707-712
  • 57 Hong C, Simons D. Pathophysiologic and electrophysiologic mechanisms of myofascial trigger points.  Arch Phys Med Rehabil. 1998;  79 863-872
  • 58 Hubbard D, Berkoff G. Myofascial trigger points show spontaneous needle EMG activity.  Spine. 1993;  18 1803-1807
  • 59 Acquadro M A, Borodic G E. Treatment of myofascial pain with botulinum A toxin.  Anesthesiology. 1994;  80 705-706
  • 60 Cheshire W P, Abashian S W, Mann J D. Botulinum toxin in the treatment of myofascial pain syndrome.  Pain. 1994;  59 65-69
  • 61 Yue S K. Initial experience in the use of botulinum-toxin A for the treatment of myofascial related muscle dysfunctions.  J Musculoscelet Pain. 1995;  3 (Suppl 1) 22
  • 62 Monsivais J J, Monsivais D B. Botulinum toxin in painful syndromes.  Hand Clin. 1996;  12 787-789
  • 63 Alo K M, Yland M J, Kramer D L. et al . Botulinum toxin in the treatment of myofascial pain.  The Pain Clinic. 1997;  10 107-116
  • 64 Galate J F, Childers M K, Gnatz S. Effectiveness of botulinum toxin in refractory piriformis muscle syndrome.  Arch Phys Med Rehabil. 1997;  78 1041
  • 65 Wheeler A H, Goolkasian P, Gretz S S. A randomized, double-blind, prospective pilot study of botulinum toxin injection for refractory, unilateral, cervicothoracic, paraspinal, myofascial pain syndrome.  Spine. 1998;  23 1662-1666
  • 66 Diaz J H, Gould H J. Management of post-thoracotomy pseudoangina and myofascial pain with botulinum toxin.  Anesthesiology. 1999;  91 877-899
  • 67 Jordan S E, Ahn S S, Freischlag J A. et al . Selective botulinum chemodenervation of the scalene muscles for treatment of neurogenic thoracic outlet syndrome.  Ann Vasc Surg. 2000;  14 365-369
  • 68 Lutze M A. CT-gestützte Injektionen von Botulinumtoxin A beim myofaszialen Schmerzsyndrom.  Schmerz. 2000;  Suppl 1 91
  • 69 Porta M. A comparative trial of botulinum toxin type A and methylprednisolone for the treatment of myofascial pain syndrome and pain from chronic muscle spasm.  Pain. 2000;  85 101-105
  • 70 Nouwen A, Bush C. The relationship between paraspinal EMG and chronic low back pain.  Pain. 1984;  20 109-123
  • 71 Foster L, Clapp L, Erickson M, Jabbari B. Botulinum toxin A and chronic low back pain: a randomized, double-blind study.  Neurology. 2001;  56 1290-1293
  • 72 Paulson G W, Gill W. Botulinum toxin is unsatisfactory therapy for fibromyalgia.  Mov Disord. 1996;  11 459
  • 73 Asherson R A, Pascoe L. The use of botulinum toxin-A in the treatment of patients with fibromyalgia.  J Rheumatol. 2001;  28 1740
  • 74 Göbel H, Petersen-Braun M, Soyka D. The epidemiology of headache in Germany: A nationwide survey of a representative sample on the basis of the headache classification of the International Headache Society.  Cephalalgia. 1994;  14 97-106
  • 75 Jensen R. Pathophysiological mechanisms of tension-type headache: a review of epidemiological and experimental studies.  Cephalalgia. 1999;  19 602-621
  • 76 Jensen R, Olesen J. Tension-type headache: an update on mechanisms and treatment.  Curr Opin Neurol. 2000;  13 285-289
  • 77 Olesen J. Clinical and pathophysiological observations in migraine and tension-type headache explained by integration of vascular, supraspinal and myofascial inputs.  Pain. 1991;  46 125-132
  • 78 Pikoff H. Is the muscular model of headache still viable? A review of conflicting data.  Headache. 1984;  24 186-198
  • 79 Zwart J A, Bovim G, Sand T, Sjaastad O. Tension headache: botulinum toxin paralysis of temporal muscles.  Headache. 1994;  34 458-462
  • 80 Relja M A, Korsic M. Treatment of tension-type headache by local injection of botulinum toxin.  Eur J Neurol. 1997;  4 (Suppl 2) 71-73
  • 81 Wheeler A H. Botulinum toxin A, adjunctive therapy for refractory headaches associated with pericranial muscle tension.  Headache. 1998;  38 468-471
  • 82 Göbel H, Lindner V, Krack P. et al . Treatment of chronic tension-type headache with botulinum toxin.  Cephalalgia. 1999;  19 455
  • 83 Schulte-Mattler W J, Wieser T, Zierz S. Treatment of tension-type headache with botulinum toxin: a pilot study.  Eur J Med Res. 1999;  4 183-186
  • 84 Relja M A, Korsic M. Treatment of tension-type headache by injections with botulinum toxin type A: a double-blind placebo-controlled study.  Neurology. 1999;  52 (Suppl 2) 203
  • 85 Smuts J A, Baker M K, Smuts H M. Botulinum toxin type A as prophylactic treatment in chronic tension-type headache.  Cephalalgia. 1999;  19 454
  • 86 Porta M. A comparative trial of botulinum toxin A and methylprednisolone for the treatment of tension-type headache.  Curr Rev Pain. 2000;  4 31-35
  • 87 Relja M A. Treatment of tension-type headache with botulinum toxin: 1-year-follow-up.  Cephalalgia. 2000;  20 336
  • 88 Rollnik J D, Tanneberger O, Schubert M. et al . Treatment of tension-type headache with botulinum toxin type A: a double-blind, placebo-controlled study.  Headache. 2000;  40 300-305
  • 89 Wollina U. Botulinum A toxin for wrinkles: release from tension headache.  J Eur Acad Dermatol Venereol. 2000;  14 142-143
  • 90 Schmitt W J, Slowey E, Fravi N. et al . Effect of botulinum toxin A injections in the treatment of chronic tension-type headache: a double-blind, placebo-controlled trial.  Headache. 2001;  41 658-664
  • 91 Diener H C, Brune K, Gerber W. et al . Behandlung der Migräneattacke und Migräneprophylaxe.  Dtsch Ärztebl. 1997;  94 3092-3102
  • 92 Nelson C F. The tension headache, migraine headache continuum: a hypothesis.  J Manipulative Physiol Ther. 1994;  17 156-167
  • 93 Brin M F, Swope D M, O'Brien C. et al . Botox® for migraine: double-blind, placebo-controlled, region-specific evaluation.  Cephalalgia. 2000;  20 421-422
  • 94 Mauskop A, Basdeo R. Botulinum toxin A is an effect prophylactic therapy of migraines.  Cephalalgia. 2000;  20 422
  • 95 Silberstein S, Mathew N, Saper J, Jenkins S. Botulinum toxin type A as a migraine preventive treatment. For the BOTOX Migraine Clinical Research Group.  Headache. 2000;  40 445-450
  • 96 Smuts J A, Barnard P WA. Botulinum toxin type A in the treatment of headache syndromes: a clinical report of 79 patients.  Cephalalgia. 2000;  20 332
  • 97 Klapper J A, Mathew N T, Klapper A, Kailasam J. Botulinum toxin type A (BTX-A) for the prophylaxis of chronic daily headache.  Cephalalgia. 2000;  20 291-292
  • 98 Harris M, Feinmann C, Wise M, Treasure F. Temporomandibular joint and orofacial pain: clinical and medicolegal management problems.  Br Dent J. 1993;  174 129-136
  • 99 Headache classification committee of the international headache society . Classification and diagnosis criteria for headache disorders, cranial neuralgia and facial pain.  Cephalalgia. 1988;  8 (Suppl 7) 1-92
  • 100 Ginies P R, Fraimout J L, Kong A. et al .Treatment of cluster headache by subcutaneous injection of botulinum toxin. 8. World Congress on Pain 1996 Poster presentation: 50
  • 101 Freund B J, Schwartz M. The use of Botulinum toxin A in the treatment of refractory cluster headache: case reports.  Cephalalgia. 2000;  20 329-330
  • 102 Girdler N M. Use of botulinum toxin to alleviate facial pain (letter).  Brit J Hospital Med. 1994;  52 362-363
  • 103 Finn S, Ryan P, Sleeman D. The medical management of masseteric hypertrophy with botulinum toxin.  J Ir Dent Assoc. 2000;  46 84-86
  • 104 Freund B, Schwartz M, Symington J M. Botulinum toxin: new treatment for temporomandibular disorders.  Br J Oral Maxillofac Surg. 2000;  38 466-471
  • 105 von Lindern J. Type A botulinum toxin in the treatment of chronic facial pain associated with temporo-mandibular dysfunction.  Acta Neurol Belg. 2001;  101 39-41
  • 106 Hobson D E, Gladish D F. Botulinum toxin injection for cervicogenic headache.  Headache. 1997;  37 253-255
  • 107 Freund B J, Schwartz M. Treatment of whiplash associated neck pain with botulinum toxin-A: report of 8 cases.  J Rheumatol. 1999;  26 756-758
  • 108 Freund B J, Schwartz M. Treatment of chronic cervical-associated headache with botulinum toxin A: a pilot study.  Headache. 2000;  40 231-236
  • 109 Pollmann W, Keidel M, Pfaffenrath V. Headache and the cervical spine: a critical review.  Cephalalgia. 1997;  17 801-816
  • 110 Hoogerwerf W A, Pasricha P J. Botulinum toxin for spastic gastrointestinal disorders.  Baillieres Best Pract Res Clin Gastroenterol. 1999;  13 131-143
  • 111 Cuillere C, Ductrotte P, Zerbib F. et al . Achalasia: outcome of patients treated with intrasphincteric injection of botulinum toxin.  Gut. 1997;  41 87-92
  • 112 Pasricha P J, Ravich W J, Hendrix T R. et al . Intrasphincteric botulinum toxin for the treatment of achalasia.  N Engl J Med. 1995;  322 774-778
  • 113 Pasricha P J, Miskovsky E P, Kalloo A N. Intrasphincteric injection of botulinum toxin for suspected sphincter of Oddi dysfunction.  Gut. 1994;  35 1319-1321
  • 114 Sherman S, Kopecky K K, Brashear A, Lehmann G A. Percutaneus celiac plexus block with botulinum toxin A did not help the pain of chronic pancreatitis.  J Clin Gastroenterol. 1995;  20 343-344
  • 115 Wehrmann T, Seifert H, Seipp M. et al . Endoscopic injection of botulinum toxin for biliary sphincter of Oddi dysfunction.  Endoscopy. 1998;  30 702-707
  • 116 Muehldorfer S, Hahn E. Botulinum toxin injection as a diagnostic tool for verification of Oddi dysfunction causing recurrent pancreatitis.  Endoscopy. 1997;  29 120-124
  • 117 Brisinda G, Maria G, Bentivoglio A R. et al . A comparison of injections of botulinum toxin and topical nitroglycerin ointment for the treatment of chronic anal fissure.  N Engl J Med. 1999;  341 65-69
  • 118 Jost W. One hundred cases of anal fissure treatmed with botulin toxin: early and long-term results.  Dis Colon Rectum. 1997;  40 1029-1032
  • 119 Maria G, Cassetta E, Gui D. A comparison of botulinum toxin and saline for the treatment of chronic anal fissure.  N Engl J Med. 1998;  338 217-220
  • 120 Christiansen J, Bruun E, Skjoldbye B, Hagen K. Chronic idiopathic anal pain: analysis of ultrasonography, pathology, and treatment.  Dis Colon Rectum. 2001;  44 661-665
  • 121 Zermann D, Ishigoka M, Schubert J, Schmidt R. Perisphincteric injection of botulinum toxin type A. A treatment option for patients with chronic prostatic pain?.  Eur Urol. 2000;  38 393-399

Dr. med. T. Probst
Prof. Dr. med. E. Kunesch

Klinik für Neurologie und Poliklinik Universität Rostock

Gehlsheimer Straße 20

18147 Rostock

Email: thomas.probst@med.uni-rostock.de

Email: erwin.kunesch@med.uni-rostock.de

    >