Download PDF
Fortschr Neurol Psychiatr 2002; 70(2): 88-94
DOI: 10.1055/s-2002-19922
Originalarbeit
Georg Thieme Verlag Stuttgart · New York

Neuropathische Schmerzen - Mechanismen und Therapie

Mechanism-Based Treatment Principles of Neuropathic PainF.  Birklein1
  • 1Neurologische Universitätsklinik Mainz (Direktor: Prof. Dr. M. Dieterich)
Diese Arbeit wurde von der DFG, SFB 353, C3 und vom Forschungsnetzwerk „Neuropathischer Schmerz” des BMBF unterstützt.
Further Information

Publication History

Publication Date:
01 February 2002 (online)

    Permissions and Reprints

Zusammenfassung

Neuropathische Schmerzen treten dann auf, wenn das Nervensystem selbst geschädigt ist. In der gängigen Klassifikation werden neuropathische Schmerzen noch nach deren Ätiologie eingeteilt. Durch die Forschung der letzten Jahre gelang es jedoch, die wichtigsten molekularen Mechanismen neuropathischer Schmerzen aufzuklären. Es hat sich dabei gezeigt, dass diese Mechanismen prinzipiell unabhängig von der Ätiologie der Nervenschädigung sind. Die wichtigsten Mechanismen sind die Akkumulation von spannungsabhängigen Na+-Kanälen im verletzten Nerv, die pathologische Kopplung zwischen sympathischen und nozizeptiven Axonen, die Disinhibition der Schmerzempfindung auf Rückenmarksebene, die zentrale (spinale) und die periphere nozizeptive Sensibilisierung. Gegen jeden einzelnen Mechanismus gibt es bereits heute therapeutische Optionen. Das Ziel einer erfolgreichen Schmerztherapie muss also sein, individuelle Schmerzmechanismen und nicht ätiologische Krankheitsentitäten zu bekämpfen. Die Aufgaben der klinischen Forschung in den nächsten Jahren liegen darin, dazu die nötigen Instrumentarien zu liefern. Nur so wird jeder Patient mit neuropathischen Schmerzen die für ihn effiziente Therapie bekommen können.

Abstract

Traditionally, neuropathic pain has been classified due to aetiology of nerve damage-traumatic, inflammatory or metabolic, for instance. Based on this classification, pain therapy often is insufficient. Recent research revealed different mechanisms, which are responsible for the generation of pain after nerve lesion. These mechanisms seem to be independent of aetiology of the nerve damage. The most important mechanisms are accumulation of sodium channels on injured nerves, pathological sympatho-afferent coupling, disinhibition of nociception and central or peripheral nociceptive sensitisation. Each individual mechanism could be treated specifically by current available drugs, or by non-drug therapy. However, future research has to focus on exploring tools to recognise individual pain mechanisms in single patients. Thereby treatment will become more effective.

Literatur

  • 1 Amir R, Michaelis M, Devor M. Membrane potential oscillations in dorsal root ganglion neurons: role in normal electrogenesis and neuropathic pain.  J Neurosci. 1999;  19 8589-8596
    CrossrefPubMedGoogle Scholar
  • 2 Arner S, Meyerson B A. Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain.  Pain. 1988;  33 11-23
    CrossrefPubMedGoogle Scholar
  • 3 Backonja M M. Anticonvulsants (antineuropathics) for neuropathic pain syndromes.  Clin J Pain. 2000;  16 S67-S72
    PubMedGoogle Scholar
  • 4 Baron R. Peripheral Neuropathic Pain: From Mechanisms to Symptoms.  Clin J Pain. 2000;  16 12-20
    CrossrefPubMedGoogle Scholar
  • 5 Birklein F, Weber M, Ernst M, Riedl B, Neundörfer B, Handwerker H O. Experimental tissue acidosis leads to increased pain in complex regional pain syndrome (CRPS).  Pain. 2000;  87 227-234
    CrossrefPubMedGoogle Scholar
  • 6 Birklein F, Weber M, Neundörfer B. Increased skin lactate in complex regional pain syndrome: evidence for tissue hypoxia?.  Neurology. 2000;  55 1213-1215
    PubMedGoogle Scholar
  • 7 Brau M E, Dreimann M, Olschewski A, Vogel W, Hempelmann G. Effect of Drugs Used for Neuropathic Pain Management on Tetrodotoxin-resistant Na+Currents in Rat Sensory Neurons.  Anesthesiology. 2001;  94 137-144
    PubMedGoogle Scholar
  • 8 Drummond P D, Finch P M, Edvinsson L, Goadsby P J. Plasma neuropeptide Y in the symptomatic limb of patients with causalgic pain.  Clin Aut Res. 1994;  4 113-116
    PubMedGoogle Scholar
  • 9 Flor H, Knecht S, Wienbruch C, Pantev C, Birbaumer N, Larbig W, Taub E. Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation.  Nature. 1995;  375 482-484
    CrossrefPubMedGoogle Scholar
  • 10 Fromm G H, Terrence C F, Chattha A S. Baclofen in the treatment of trigeminal neuralgia: double-blind study and long-term follow-up.  Ann Neurol. 1984;  15 240-244
    CrossrefPubMedGoogle Scholar
  • 11 Galer B S, Rowbotham M C, Perander J, Friedman E. Topical lidocaine patch relieves postherpetic neuralgia more effectively than a vehicle topical patch: results of an enriched enrollment study.  Pain. 1999;  80 533-538
    CrossrefPubMedGoogle Scholar
  • 12 Goris R J, Dongen L M, Winters H A. Are toxic radicals involved in the pathogenesis of reflex sympathetic dystrophy?.  Free Radic Res. 1987;  3 13-18
    PubMedGoogle Scholar
  • 13 Hamza M A, White P F, Craig W F, Ghoname E S, Ahmed H E, Proctor T J, Noe C E, Vakharia A S, Gajraj N. Percutaneous electrical nerve stimulation: a novel analgesic therapy for diabetic neuropathic pain.  Diabetes Care. 2000;  23 365-370
    PubMedGoogle Scholar
  • 14 Hannington-Kiff J G. Antisympathetic drugs in limbs. In: Wall P, Melzack R (Hrsg). Textbook of Pain. Edinburgh: Chirchill livingston 1984: 566-573
    Google Scholar
  • 15 Kemler M A, Barendse G A, van Kleef M, de Vet H C, Rijks C P, Furnee C A, van den Wildenberg F A. Spinal cord stimulation in patients with chronic reflex sympathetic dystrophy.  N Engl J Med. 2000;  343 618-624
    Google Scholar
  • 16 Kingery W S. A critical review of controlled clinical trials for peripheral neuropathic pain and complex regional pain syndromes.  Pain. 1997;  73 123-139
    CrossrefPubMedGoogle Scholar
  • 17 Kingery W S, Agashe G S, Sawamura S, Davies M F, Clark J D, Maze M. Glucocorticoid Inhibition of Neuropathic Hyperalgesia and Spinal Fos Expression.  Anesth Analg. 2001;  92 476-482
    PubMedGoogle Scholar
  • 18 Koltzenburg M. Painful neuropathies.  Curr Opin Neurol. 1998;  11 515-521
    CrossrefPubMedGoogle Scholar
  • 19 Kurvers H A, Jacobs M J, Beuk R J, van den Wildenberg F A, Kitslaar P J, Slaaf D W, Reneman R S. Reflex sympathetic dystrophy: evolution of microcirculatory disturbances in time.  Pain. 1995;  60 333-340
    CrossrefPubMedGoogle Scholar
  • 20 McCleane G J. Lamotrigine in the management of neuropathic pain: a review of the literature.  Clin J Pain. 2000;  16 321-326
    PubMedGoogle Scholar
  • 21 McQuay H J, Tramer M, Nye B A, Carroll D, Wiffen P J, Moore R A. A systematic review of antidepressants in neuropathic pain.  Pain. 1996;  68 217-227
    CrossrefPubMedGoogle Scholar
  • 22 Miao F J, Janig W, Levine J. Role of sympathetic postganglionic neurons in synovial plasma extravasation induced by bradykinin.  J Neurophysiol. 1996;  75 715-724
    PubMedGoogle Scholar
  • 23 Morello C M, Leckband S G, Stoner C P, Moorhouse D F, Sahagian G A. Randomized double-blind study comparing the efficacy of gabapentin with amitriptyline on diabetic peripheral neuropathy pain.  Arch Intern Med. 1999;  159 1931-1937
    CrossrefPubMedGoogle Scholar
  • 24 Neumann S, Doubell T P, Leslie T, Woolf C J. Inflammatory pain hypersensitivity mediated by phenotypic switch in myelinated primary sensory neurons.  Nature. 1996;  384 360-364
    CrossrefPubMedGoogle Scholar
  • 25 Pan H L, Eisenach J C, Chen S R. Gabapentin suppresses ectopic nerve discharges and reverses allodynia in neuropathic rats.  J Pharmacol Exp Ther. 1999;  288 1026-1030
    PubMedGoogle Scholar
  • 26 Peiris J B, Perera G L, Devendra S V, Lionel N D. Sodium valproate in trigeminal neuralgia.  Med J Aust. 1980;  2 278
    PubMedGoogle Scholar
  • 27 Rush A M, Elliott J R. Phenytoin and carbamazepine: differential inhibition of sodium currents in small cells from adult rat dorsal root ganglia.  Neurosci Lett. 1997;  226 95-98
    CrossrefPubMedGoogle Scholar
  • 28 Sato J, Perl E R. Adrenergic excitation of cutaneous pain receptors induced by peripheral nerve injury.  Science. 1991;  251 1608-1610
    PubMedGoogle Scholar
  • 29 Sindrup S H, Andersen G, Madsen C, Smith T, Brosen K, Jensen T S. Tramadol relieves pain and allodynia in polyneuropathy: a randomised, double-blind, controlled trial.  Pain. 1999;  83 85-90
    CrossrefPubMedGoogle Scholar
  • 30 Sindrup S H, Gram L F, Brosen K, Eshoj O, Mogensen E F. The selective serotonin reuptake inhibitor paroxetine is effective in the treatment of diabetic neuropathy symptoms.  Pain. 1990;  42 135-144
    CrossrefPubMedGoogle Scholar
  • 31 Tal M, Wall P D, Devor M. Myelinated afferent fiber types that become spontaneously active and mechanosensitive following nerve transection in the rat.  Brain Res. 1999;  824 218-223
    CrossrefPubMedGoogle Scholar
  • 32 Tandan R, Lewis G A, Badger G B, Fries T J. Topical capsaicin in painful diabetic neuropathy. Effect on sensory function.  Diabetes Care. 1992;  15 15-18
    PubMedGoogle Scholar
  • 33 Tran K M, Frank S M, Raja S N, El-Rahmany H K, Kim L J, Vu B. Lumbar sympathetic block for sympathetically maintained pain: changes in cutaneous temperatures and pain perception.  Anesth Analg. 2000;  90 1396-1401
    PubMedGoogle Scholar
  • 34 Verdugo R J, Campero M, Ochoa J L. Phentolamine sympathetic block in painful polyneuropathies. II. Further questioning of the concept of ‘sympathetically maintained pain’.  Neurology. 1994;  44 1010-1014
    PubMedGoogle Scholar
  • 35 Wallace M S, Ridgeway B M, Leung A Y, Gerayli A, Yaksh T L. Concentration-effect relationship of intravenous lidocaine on the allodynia of complex regional pain syndrome types I and II.  Anesthesiology. 2000;  92 75-83
    CrossrefPubMedGoogle Scholar
  • 36 Watson C P, Babul N. Efficacy of oxycodone in neuropathic pain: a randomized trial in postherpetic neuralgia.  Neurology. 1998;  50 1837-1841
    PubMedGoogle Scholar
  • 37 Woolf C J, Mannion R J. Neuropathic pain: aetiology, symptoms, mechanisms, and management.  Lancet. 1999;  353 1959-1964
    CrossrefPubMedGoogle Scholar
  • 38 Woolf C J, Salter M W. Neuronal plasticity: increasing the gain in pain.  Science. 2000;  288 1765-1769
    CrossrefPubMedGoogle Scholar
  • 39 Woolf C J, Shortland P, Coggeshall R E. Peripheral nerve injury triggers central sprouting of myelinated afferents.  Nature. 1992;  355 75-78
    CrossrefPubMedGoogle Scholar
  • 40 Xu X J, Puke M J, Verge V M, Wiesenfeld-Hallin Z, Hughes J, Hokfelt T. Up-regulation of cholecystokinin in primary sensory neurons is associated with morphine insensitivity in experimental neuropathic pain in the rat.  Neurosci Lett. 1993;  152 129-132
    CrossrefPubMedGoogle Scholar
  • 41 Ziegler D, Hanefeld M, Ruhnau K J, Hasche H, Lobisch M, Schutte K, Kerum G, Malessa R. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy.  Diabetes Care. 1999;  22 1296-1301
    PubMedGoogle Scholar

PD Dr. F. Birklein

Neurologische Universitätsklinik

Langenbeckstraße 1

55101 Mainz

Email: birklein@neurologie.klinik.uni-mainz.de

      >