Download PDF
Nervenheilkunde 2004; 23(05): 279-296
DOI: 10.1055/s-0038-1626376
Original- und Übersichtsarbeiten - Original and Review Articles
Schattauer GmbH

Behandlung neuropathischer Schmerzen

Angriffspunkte und Wirkmechanismen von ArzneistoffenMode of action of drugs for treating neuropathic pain disorders
A. Ziegler
1   Institut für Pharmakologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel
› Author Affiliations
Further Information

Publication History

Publication Date:
31 January 2018 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Die Konzepte zur Entstehung und Aufrechterhaltung neuropathischer Schmerzzustände ermöglichen es, die potenziell relevanten Eigenschaften und Wirkmechanismen der Arzneistoffe zu definieren, die zur Behandlung der unterschiedlichen Formen des neuropathischen Schmerzes eingesetzt werden. Sie machen darüber hinaus verständlich, warum die zur Behandlung von Nozizeptorschmerzen eingesetzten Pharmaka sich bei Formen des neuropathischen Schmerzes als weniger wirksam erweisen. Auch werden Strategien erkennbar, wie diese Ineffektivität überkommen und einer Tachyphylaxie des gewünschten analgetischen Effektes begegnet werden kann. Es zeichnet sich als durchgängiges Prinzip ab, dass sich hoch selektiv wirkende Pharmaka in der Therapie nicht bewähren, sondern gleichermaßen wirksame und verträgliche Arzneimittel durch bestimmte Muster unterschiedlicher pharmakologischer Effekte gekennzeichnet sind.

Summary

Major progress in research on the etiology and pathophysiology of neuropathic pain allows to define targets and mechanisms of action of those drugs used to treat the different forms of neuropathic pain. The concepts explain why drugs known to cause analgesia in nociceptor pain are less active in neuropathic pain. Strategies can be developed to change these less effective to active drugs und to avoid the development of tachyphylaxis. The efforts to develop highly selective and most specific drugs for treating neuropathic pain were successfull, the highly specific acting drugs are, however, consistently causing intolerable side effects. A pattern of different pharmacological activities seems to be required for equally effective and tolerable remedies.

Schlüsselwörter

Neuropathischer Schmerz - Arzneistoffe - Wirkmechanismus - pharmakologische Angriffspunkte

Keywords

Neuropathic pain - drug treatment - mode of action - targets of pharmacological intervention
 

  • Literatur

  • 1 Matzner O, Devor M. Na+ conductance and the threshold for repetitive neuronal firing. Brain Res 1992; 597: 349-59.
    Google Scholar
  • 2 Cummins TR, Waxman SG. Downregulation of tetrodotoxin-resistant sodium currents and upregulation of a rapidly repriming tetrodotoxin-sensitive sodium current in small spinal sensory neurons after nerve injury. J Neurosci 1997; 18: 9607-16.
    Google Scholar
  • 3 Akopian AN, Souslova V, England S, Okuse K, Ogata N, Ure J. et al. The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways. Nature Neurosciene 1999; 02: 541-8.
    Google Scholar
  • 4 Dib-Haij SD, Fjell J, Cummins TR, Zheng Z, Fried K, La Motte R. et al. Plasticity of sodium channel expression in DRG neurons in the chronic constriction injury model of neuropathic pain. Pain 1999; 83: 591-600.
    CrossrefPubMedGoogle Scholar
  • 5 Caterina JM, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 1997; 389: 816-24.
    CrossrefPubMedGoogle Scholar
  • 6 Kress M, Zeilhofer HU. Capsaicin, protons and heat: new excitement about nociceptors. Trends Pharmacol Sci 1999; 20: 112-8.
    CrossrefPubMedGoogle Scholar
  • 7 Holzer P. Capsaicin: cellular targets, mechanism of action, and selectivity for thin sensory neurons. Pharmacol Rev 1991; 43: 144-201.
    Google Scholar
  • 8 Docherty RJ, Robertson B, Bevan S. Capsaicin causes prolonged inhibition of voltage calcium currents in adult rat dorsal root ganglion neurons in culture. Neuroscience 1991; 40: 513-21.
    CrossrefPubMedGoogle Scholar
  • 9 Watson CR, Tyler KL, Bickers DR, Millikan LE, Smith S E. C. A randomised, vehicle controlled trial of topical capsaicin in the treatment of postherpetic neuralgia. Clin Ther 1993; 15: 510-26.
    PubMedGoogle Scholar
  • 10 The capsaicin study group. Treatment of painful diabetic neuropathy with topical capsaicin. Arch Int Med 1991; 151: 2225.
    CrossrefGoogle Scholar
  • 11 Bernstein JE, Korman NJ, Bickers DR, Dahl MV. et al. Topical capsaicin treatment for chronic postherpetic neuralgia. J Am Acad Dermatol 1998; 21: 265-70.
    Google Scholar
  • 12 Szallasi A, Blumberg PM. Vanilloid (capsaicin) receptors and mechanisms. Pharmacol Rev 1999; 51: 159-211.
    PubMedGoogle Scholar
  • 13 Urban L, Campbell EA, Panesar M PS, Chaudhry N, Kane S, Buchheit K-H. et al. In vivo pharmacology of SDZ 249-665, a novel, nonpungent capsaicin analogue. Pain 2000; 89: 65-74.
    CrossrefPubMedGoogle Scholar
  • 14 McLean MJ, Macdonald RL. Carbamazepine and 10,11.epoxycarbamazepine produce useand voltage-dependent limitations of rapidly firing action potentials of mouse central neurons in cell culture. J Pharmacol Exp Ther 1986; 238: 727-38.
    PubMedGoogle Scholar
  • 15 Tanelian DL, Cousins MJ. Combined neurogenic and nociceptive pain in a patient with pancoast tumor managed by epidural hydromorphone and oral carbamazepine. Pain 1989; 36: 85-8.
    CrossrefPubMedGoogle Scholar
  • 16 Tremont-Lukats IW C, Backonja M-M. Anticonvulsants for neuropathic pain syndromes. Drugs 2000; 60: 1029-52.
    CrossrefPubMedGoogle Scholar
  • 17 Drewes AM, Andreasen A, Poulsen LH. Valproat for treatment of chronic central pain after spinal cord injury: a double-blind, crossover study. Paraplegia 1994; 32: 565-9.
    PubMedGoogle Scholar
  • 18 Birch PJ. Tachykinins: Central and peripheral effects. In: Dickenson A, Besson J-M. (eds). Handbook exp Pharmacol: The pharmacology of pain. Berlin, Heidelberg: Springer; 1997: 117-33.
    Google Scholar
  • 19 Laird JMA. Tachykinin NK1 receptors are required for pain and hyperalgesia to neurogenic stimuli: studies in NK1 receptor knockout mice. Regul Pept 1999; 80: 116.
    Google Scholar
  • 20 de Koninck Y, Henry JL. Substance P-mediated slow excitatory postsynaptic potential elicited in dorsal horn neurons in vivo by noxious stimulation. Proc Natl Acad Sci USA 1991; 88: 11344-8.
    CrossrefPubMedGoogle Scholar
  • 21 Rupniak NMJ, Kramer MS. Discovery of the anti-depressant and anti-emetic efficacy of substance P (NK1) antagonists. Trends Pharmacol Sci 1999; 20: 485-90.
    CrossrefPubMedGoogle Scholar
  • 22 Hill RG. NK1 (substance P) receptor antagonists - why are they not analgesic in humans?. Trends Pharmacol Sci 2000; 21: 244-6.
    CrossrefPubMedGoogle Scholar
  • 23 Villanueva L. Is there a gap between preclinical and clinical studies of analgesia?. Trends Pharmacol Sci 2000; 20: 461-2.
    Google Scholar
  • 24 Urban LA, Fox AJ. NK1 receptor antagonists – are they really without effect in the pain clinic?. Trends Pharmacol Sci 2000; 21: 462-4.
    CrossrefPubMedGoogle Scholar
  • 25 Dickenson A. Mechanisms of central hypersensitivity: excitatory amino acid mechanisms and their control. In: Dickenson A, Besson J-M. (eds). Handbook of Pharmacology: Pharmacology of pain. Berlin, Heidelberg: Springer; 1996: 167-210.
    Google Scholar
  • 26 Vanderschuren LJ, Schoffelmeer AN, Mulder AH. et al. Dizocilpine (MK801): use or abuse?. Trends Pharmacol Sci 1998; 19: 79-81.
    CrossrefPubMedGoogle Scholar
  • 27 Bhana N GK, McClellan J. Dexmedetomidine. Drugs 2000; 59: 263-8.
    CrossrefPubMedGoogle Scholar
  • 28 Benedetti F, Vighetti S, Amanzio M, Casadio C, Oliaro A, Bergamasco B. et al. Dose-response relationship of opioids in nociceptive and neuropathic postoperative pain. Pain 1998; 74: 205-11.
    CrossrefPubMedGoogle Scholar
  • 29 Puttfarcken P, Werlin LL, Brown SR, Cote TE, Cox BM. Sodium regulation of agonist binding at opioid receptors I effects of sodium replacement on binding at µ and d-type receptors in 7315C and NG108-15 cells and cell membranes. Mol Pharmacol 1986; 30: 81-9.
    PubMedGoogle Scholar
  • 30 Pert CB, Snyder SH. Opiate receptor binding of agonist and antagonist affected differentially by sodium. Mol Pharmacol 1974; 10: 868-79.
    Google Scholar
  • 31 Crain SM, Shen K-F. Modulation of opioid analgesia, tolerance and dependence by Gscoupled, GM1 ganglioside regulated opioid receptor functions. Trends Pharmacol Sci 1998; 19: 358-65.
    CrossrefPubMedGoogle Scholar
  • 32 Freiman TM, Kukolja J, Heinemeyer J, Eckhardt K AH, Rominger A, Dooley DJ. et al. Modulation of K+-evoked [3H]-noradrenaline release from rat and human brain slices by gabapentin: involvement of KATP channels. Naunyn Schmiedebergs Arch Pharmacol 2001; 363: 537-42.
    CrossrefPubMedGoogle Scholar
  • 33 Stefani A, Spadoni F, Giacomini P, Lavaroni F G. B. The effects of gabapentin on different ligand- and voltage-gated currents in isolated cortical neurons. Epilepsy Res 2001; 43: 239-48.
    CrossrefPubMedGoogle Scholar
  • 34 Backonja M, Beydoun QA, Edwards KR, Schwartz SL, Fonseca V, Hes M. et al. Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus. J Am Med Ass 1998; 280: 1831-6.
    CrossrefPubMedGoogle Scholar
  • 35 Pancrazio JJ, Kamatchi GL, Roscoe AK, Lynch C. Inhibition of neuronal Na+ channels by antidepressant drugs. J Pharmacol Exp Therap 1998; 284: 208-14.
    Google Scholar
  • 36 Wiesenfeld-Halin Z. Combined opioid-NMDA antagonist therapies. Drugs 1998; 55: 1-4.
    PubMedGoogle Scholar