Skip to main content
SpringerLink
Log in

Der Capsaicinrezeptor

Ein TRP zur Transduktion schmerzhafter Reize

The capsaicin receptor

“TRPing” transduction for painful stimuli

  • Übersichten
  • Published:
Der Schmerz Aims and scope Submit manuscript

Zusammenfassung

Der Capsaicinrezeptor TRPV1, der ursprünglich als Rezeptor für scharfe Gewürze identifiziert wurde, ist ein polymodales Sensormolekül, das spezifisch durch schmerzhafte chemische und thermische Reize aktiviert wird. TRPV1 ist jedoch nicht nur an der Detektion akut schmerzhafter Reize beteiligt, sondern spielt auch eine zentrale Rolle im Rahmen von Entzündungsprozessen. Durch anhaltende funktionelle Sensibilisierung sowie eine gesteigerte Expression ist dieser Membrankanal daher auch an der Entstehung und Aufrechterhaltung chronischer Schmerzen beteiligt. Somit stellt TRPV1 eine exzellente Zielstruktur für eine rationale pharmakologische Schmerztherapie dar. Neben seiner Beteiligung an Nozizeption und Schmerz scheint TRPV1 noch zahlreiche weitere physiologische und pathophysiologische Funktionen zu besitzen. Die Aktivierung von TRPV1 trägt kausal zur Ätiologie und Pathogenese verschiedener entzündlicher Erkrankungen bei, z. B. des Magen-Darm-Trakts, der Blase und des respiratorischen Systems. Das therapeutische Potenzial einer pharmakologischen Manipulation des TRPV1 könnte somit über eine symptomatische Schmerztherapie hinausgehen.

Abstract

The capsaicin receptor TRPV1, once discovered as a receptor for pungent spices, is a polymodal sensor molecule for painful chemical and thermal stimuli. However, TRPV1 plays an important role not only for the integration of acute painful stimuli but also in the genesis of inflammatory processes. The persistent functional sensitization of TRPV1 as well as an up-regulation of its expression may contribute to the development and maintenance of chronic pain states. Thus, TRPV1 is an excellent target for a rational pharmacological treatment of pain. Several additional physiological and pathophysiological functions of TRPV1 are assumed beyond nociception and pain. Activation of TRPV1 seems to contribute to the etiology and pathogenesis of inflammatory diseases concerning, e.g., the gastrointestinal tract, the bladder, and the respiratory system. Therefore, the therapeutic potential of a pharmacological manipulation of TRPV1 may not be restricted to a symptomatic therapy of pain.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2

Literatur

  1. Agopyan N, Head J, Yu S, Simon SA (2004) TRPV1 receptors mediate particulate matter-induced apoptosis. Am J Physiol 286:L563–572

    Google Scholar 

  2. Bortolotti M, Coccia G, Grossi G (2002) Red pepper and functional dyspepsia. N Engl J Med 346:947–948

    Article  PubMed  Google Scholar 

  3. Caterina MJ (2003) Vanilloid receptors take a TRP beyond the sensory afferent. Pain 105:5–9

    Article  PubMed  Google Scholar 

  4. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389:816–824

    Article  PubMed  Google Scholar 

  5. Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, Koltzenburg M, Basbaum AI, Julius D (2000) Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 288:306–313

    Article  PubMed  Google Scholar 

  6. Clapham DE, Runnels LW, Strübing C (2001) The TRP ion channel family. Nat Rev Neurosci 2:387–396

    PubMed  Google Scholar 

  7. Cortright DN, Szallasi A (2004) Biochemical pharmacology of the vanilloid receptor TRPV1. Eur J Biochem 271:1814–1819

    Article  PubMed  Google Scholar 

  8. Davis JB, Gray J, Gunthorpe MJ, Hatcher JP, Davey PT, Overend P, Harries MH, Latcham J, Clapham C, Atkinson K et al. (2000) Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature 405:183–187

    Article  PubMed  Google Scholar 

  9. Dinis P, Charrua A, Avelino A, Yaqoob M, Bevan S, Nagy I, Cruz F (2004) Anandamide-evoked activation of vanilloid receptor 1 contributes to the development of bladder hyperreflexia and nociceptive transmission to spinal dorsal horn neurons in cystitis. J Neurosci 24:11253–11263

    Article  PubMed  Google Scholar 

  10. Geppetti P, Trevisani M (2004) Activation and sensitisation of the vanilloid receptor: role in gastrointestinal inflammation and function. Br J Pharmacol 141:1313–1320

    Article  PubMed  Google Scholar 

  11. Ghilardi JR, Röhrich H, Lindsay TH, Sevcik MA, Schwei MJ, Kubota K, Halvorson KG, Poblete J, Chaplan SR, Dubin AE et al. (2005) Selective blockade of the capsaicin receptor TRPV1 attenuates bone cancer pain. J Neurosci 25:3126–3131

    Article  PubMed  Google Scholar 

  12. Greffrath W, Binzen U, Schwarz S, Saaler-Reinhardt S, Treede R-D (2003) Co-expression of heat sensitive vanilloid receptor subtypes in rat dorsal root ganglion neurons. Neuroreport 14:2251–2255

    Article  PubMed  Google Scholar 

  13. Hayes P, Meadows HJ, Gunthorpe MJ, Harries MH, Duckworth DM, Cairns W, Harrison DC, Clarke CE, Ellington K, Prinjha RK et al. (2000) Cloning and functional expression of a human orthologue of rat vanilloid receptor-1. Pain 88:205–215

    Article  PubMed  Google Scholar 

  14. Holzer P (2004) TRPV1 and the gut: from a tasty receptor for a painful vanilloid to a key player in hyperalgesia. Eur J Pharmacol 500:231–241

    Article  PubMed  Google Scholar 

  15. Julius D, Basbaum AI (2001) Molecular mechanisms of nociception. Nature 413:203–210

    Google Scholar 

  16. Kirschstein T, Greffrath W, Büsselberg D, Treede R-D (1999) Inhibition of rapid heat responses in nociceptive primary sensory neurons of rats by vanilloid receptor antagonists. J Neurophysiol 82:2853–2860

    PubMed  Google Scholar 

  17. Krause JE, Chenard BL, Cortright DN (2005) Transient receptor potential ion channels as targets for the discovery of pain therapeutics. Curr Opin Investig Drugs 6:48–57

    PubMed  Google Scholar 

  18. McVey DC, Schmid PC, Schmid HH, Vigna SR (2003) Endocannabinoids induce ileitis in rats via the capsaicin receptor (VR1). J Pharmacol Exp Ther 304:713–722

    PubMed  Google Scholar 

  19. Nagy I, Sántha P, Jancsó G, Urbán L (2004) The role of the vanilloid (capsaicin) receptor (TRPV1) in physiology and pathology. Eur J Pharmacol 500:351–369

    Article  PubMed  Google Scholar 

  20. Patapoutian A, Peier AM, Story GM, Viswanath V (2003) ThermoTRP channels and beyond: mechanisms of temperature sensation. Nat Rev Neurosci 4:529–539

    Google Scholar 

  21. Reeh PW, Pethö G (2000) Nociceptor exitation by thermal sensitization — a hypothesis. In: Sandkühler J, Bromm B, Gebhart GF (Hrsg) Nervous system plasticity of chronic pain. Elsevier, Amsterdam, pp 39–50

  22. Schwarz S, Greffrath W, Büsselberg D, Treede R-D (2000) Inactivation and tachyphylaxis of heat-evoked inward currents in nociceptive primary sensory neurones of rats. J Physiol 528:539–549

    Article  PubMed  Google Scholar 

  23. Szallasi A, Blumberg PM (1999) Vanilloid (capsaicin) receptors and mechanisms. Pharmacol Rev 51:159–211

    PubMed  Google Scholar 

  24. Tominaga M, Caterina MJ (2004) Thermosensation and pain. J Neurobiol 61:3–12

    Article  PubMed  Google Scholar 

  25. Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI, Julius D (1998) The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 21:531–543

    Article  PubMed  Google Scholar 

  26. Trevisani M, Smart D, Gunthorpe MJ, Tognetto M, Barbieri M, Campi B, Amadesi S, Gray J, Jerman JC, Brough SJ et al. (2002) Ethanol elicits and potentiates nociceptor responses via the vanilloid receptor-1. Nature Neurosci 5:546–551

    Google Scholar 

  27. Valenzano KJ, Sun Q (2004) Current perspectives on the therapeutic utility of VR1 antagonists. Curr Med Chem 11:3185–3202

    PubMed  Google Scholar 

  28. Van der Stelt M, Di Marzo V (2004) Endovanilloids. Eur J Biochem 271:1827–1834

    Article  PubMed  Google Scholar 

Download references

Interessenkonflikt:

Der korrespondierende Autor versichert, dass keine Verbindungen mit einer Firma, deren Produkt in dem Artikel genannt ist, oder einer Firma, die ein Konkurrenzprodukt vertreibt, bestehen.

Author information

Authors and Affiliations

  1. Institut für Physiologie und Pathophysiologie, Johannes-Gutenberg-Universität Mainz

    W. Greffrath

  2. Institut für Physiologie und Pathophysiologie, Johannes-Gutenberg-Universität, Saarstraße 21, 55099 , Mainz

    W. Greffrath

Authors
  1. W. Greffrath
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to W. Greffrath.

Additional information

Unterstützt durch die Deutsche Forschungsgemeinschaft (Tr 236/11-3) und das naturwissenschaftlich-medizinische Forschungszentrum (NMFZ).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Greffrath, W. Der Capsaicinrezeptor. Schmerz 20, 219–225 (2006). https://doi.org/10.1007/s00482-005-0440-9

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00482-005-0440-9

Schlüsselwörter

Keywords

Search

Navigation