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Vom Tiermodell zur Diabeteskomplikation

Gibt es eine an der Schmerzpathogenese orientierte Therapie bei diabetischer Polyneuropathie?

From animal model to diabetic complications

Is there a therapy for diabetic polyneuropathy based on the pathogenesis of pain?

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Zusammenfassung

Die Prävalenz der diabetischen Neuropathie liegt bei etwa 1/3 aller Diabetiker. Häufig führt diese Neuropathie zu chronischen Schmerzen. Medikamentöse Therapieoptionen (nach aktuellen Leitlinien primär Gabapentin, Pregabalin, trizyklische Antidepressiva) wurden empirisch gefunden, und nicht anhand des Wirkmechanismus. Seit 20 Jahren wird eine an der Schmerzpathogenese orientierte Therapie gefordert. Mangelnder Forschritt auf diesem Gebiet ist zumindest teilweise dadurch erklärbar, dass die Tiermodelle nicht dem klinischen Erscheinungsbild beim Patienten entsprechen. Tiermodelle konzentrieren sich auf gesteigerte Reaktionen auf mechanische Reize, die aber nur bei weniger als 20% der Patienten auftreten. Patienten berichten hauptsächlich über Spontanschmerz, und die klinische Untersuchung zeigt Sensibilitätsausfälle für Berührung, Kälte und Nadelreize.

Abstract

Approximately 1/3 of all diabetic patients develop a peripheral neuropathy, which often leads to chronic pain. First-line pharmacological treatments according to current guidelines (gabapentin, pregabalin, tricyclic antidepressants) were found empirically and not prospectively according to their mode of action. For 20 years it has been a postulate to develop treatment approaches according to the pathophysiological mechanisms of painful diabetic polyneuropathy. The lack of progress in this field is at least partially due to a mismatch between animal models and patient phenotypes. Animal models focus on increased responsiveness to mechanical stimuli, which is present in less than 20% of patients. Patients report mainly ongoing pain accompanied by sensory loss to touch, cold and pinprick.

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Literatur

  1. Amir R, Michaelis M, Devor M (1999) Membrane potential oscillations in dorsal root ganglion neurons: role in normal electrogenesis and neuropathic pain. J Neurosci 19:8589–8596

    PubMed  CAS  Google Scholar 

  2. Apfel SC, Asbury AK, Bril V et al (2001) Positive neuropathic sensory symptoms as endpoints in diabetic neuropathy trials. J Neurol Sci 189:3–5

    Article  PubMed  CAS  Google Scholar 

  3. Attal N, Cruccu G, Haanpää M et al (2006) EFNS guidelines on pharmacological treatment of neuropathic pain. Eur J Neurol 13:1153–1169

    Article  PubMed  CAS  Google Scholar 

  4. Baron R (2006) Mechanisms of disease: neuropathic pain-a clinical perspective. Nat Clin Pract Neurol 2:95–106

    Article  PubMed  Google Scholar 

  5. Burke D, Kiernan MC, Bostock H (2001) Excitability of human axons. Clin Neurophysiol 112:1575–1585

    Article  PubMed  CAS  Google Scholar 

  6. Calcutt NA (2002) Potential mechanisms of neuropathic pain in diabetes. Int Rev Neurobiol 50:205–228

    Article  PubMed  CAS  Google Scholar 

  7. Calcutt NA, Cooper ME, Kern TS, Schmidt AM (2009) Therapies for hyperglycaemia-induced diabetic complications: from animal models to clinical trials. Nat Rev Drug Discov 8:417–429

    Article  PubMed  CAS  Google Scholar 

  8. Chen SR, Pan HL (2002) Hypersensitivity of spinothalamic tract neurons associated with diabetic neuropathic pain in rats. J Neurophysiol 87:2726–2733

    PubMed  Google Scholar 

  9. Davies A, Hendrich J, Van Minh AT et al (2007) Functional biology of the alpha(2)delta subunits of voltage-gated calcium channels. Trends Pharmacol Sci 28:220–228

    Article  PubMed  CAS  Google Scholar 

  10. Dellemijn P (1999) Are opioids effective in relieving neuropathic pain? Pain 80:453–462

    Article  PubMed  CAS  Google Scholar 

  11. Eisenberg E, McNicol ED, Carr DB (2005) Efficacy and safety of opioid agonists in the treatment of neuropathic pain of nonmalignant origin: systematic review and meta-analysis of randomized controlled trials. JAMA 293:3043–3052

    Article  PubMed  CAS  Google Scholar 

  12. Fox A, Eastwood C, Gentry C et al (1999) Critical evaluation of the streptozotocin model of painful diabetic neuropathy in the rat. Pain 81:307–316

    Article  PubMed  CAS  Google Scholar 

  13. Jensen TS, Hansson P (2006) Chapter 34 Classification of neuropathic pain syndromes based on symptoms and signs. Handb Clin Neurol 81:517–526

    Article  PubMed  Google Scholar 

  14. Max MB (1990) Towards physiologically based treatment of patients with neuropathic pain. Pain 42:131–133

    Article  PubMed  CAS  Google Scholar 

  15. Max MB, Kishore-Kumar R, Schafer SC et al (1991) Efficacy of desipramine in painful diabetic neuropathy: a placebo-controlled trial. Pain 45:3–9

    Article  PubMed  CAS  Google Scholar 

  16. Max MB, Lynch SA, Muir J et al (1992) Effects of desipramine, amitriptyline and fluoxetine on pain in diabetic neuropathy. N Engl J Med 326:1250–1256

    PubMed  CAS  Google Scholar 

  17. Orstavik K, Namer B, Schmidt R et al (2006) Abnormal function of C-fibers in patients with diabetic neuropathy. J Neurosci 26:11287–11294

    Article  PubMed  Google Scholar 

  18. Otto M, Bak S, Bach FW et al (2003) Pain phenomena and possible mechanisms in patients with painful polyneuropathy. Pain 101:187–192

    Article  PubMed  Google Scholar 

  19. Polydefkis M, Hauer P, Sheth S et al (2004) The time course of epidermal nerve fibre regeneration: studies in normal controls and in people with diabetes, with and without neuropathy. Brain 127:1606–1615

    Article  PubMed  Google Scholar 

  20. Rice AS, Cimino-Brown D, Eisenach JC et al (2008) Animal models and the prediction of efficacy in clinical trials of analgesic drugs: a critical appraisal and call for uniform reporting standards. Pain 139:243–247

    Article  PubMed  Google Scholar 

  21. Sang CN, Booher S, Gilron I et al (2002) Dextromethorphan and memantine in painful diabetic neuropathy and postherpetic neuralgia – Efficacy and dose-response trials. Anesthesiology 96:1053–1061

    Article  PubMed  CAS  Google Scholar 

  22. Sommer C (2003) Painful neuropathies. Curr Opin Neurol 16:623–628

    Article  PubMed  Google Scholar 

  23. Suzuki Y, Sato J, Kawanishi M, Mizumura K (2002) Lowered response threshold and increased responsiveness to mechanical stimulation of cutaneous nociceptive fibers in streptozotocin-diabetic rat skin in vitro-correlates of mechanical allodynia and hyperalgesia observed in the early stage of diabetes. Neurosci Res 43:171–178

    Article  PubMed  Google Scholar 

  24. Treede RD (2007) Quantitative sensorische Testung, Elektrophysiologische Messverfahren. In: Baron R, Strumpf M (Hrsg) Praktische Schmerztherapie. Springer, Berlin Heidelberg New York, S 75–81, 83–90

  25. Treede RD, Jensen TS, Campbell JN et al (2008) Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology 70:1630–1635

    Article  PubMed  CAS  Google Scholar 

  26. Ziegler D, Rathmann W, Dickhaus T et al; KORA Study Group (2009) Neuropathic pain in diabetes, prediabetes and normal glucose tolerance: the MONICA/KORA Augsburg Surveys S2 and S3. Pain Medicine 10:393–400

    Article  PubMed  Google Scholar 

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Interessenkonflikt

Der korrespondierende Autor weist auf folgende Beziehungen hin: R.D.T. hat Forschungsmittel, Beratungsgelder und Honorare erhalten von: Allergan, Boehringer Ingelheim, Bundesministerium für Bildung und Forschung, Deutsche Forschungsgemeinschaft, Glaxo Smith Kline, Grünenthal, Lilly, Merck, Sharpe & Dohme, Pfizer, Sanofi, Schwarz und US National Institutes of Health.

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  1. Lehrstuhl für Neurophysiologie, Zentrum für Biomedizin und Medizintechnik Mannheim (CBTM), Ruprecht-Karls-Universität Heidelberg, 68167, Mannheim, Deutschland

    R.-D. Treede

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Correspondence to R.-D. Treede.

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Treede, RD. Vom Tiermodell zur Diabeteskomplikation. Diabetologe 5, 344–349 (2009). https://doi.org/10.1007/s11428-009-0392-2

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  • DOI: https://doi.org/10.1007/s11428-009-0392-2

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