Résumés
Résumé
Les canaux calciques dépendants du voltage représentent une des voies principales d’entrée du calcium dans la cellule nerveuse où ils participent activement à l’excitabilité cellulaire et aux processus moléculaires de la transmission synaptique. Ils ont, de ce fait, été depuis longtemps la cible pharmacologique d’analgésiques et ce, avant même que leur implication dans la physiologie de la nociception ait réellement été démontrée. Ces dernières années, la caractérisation moléculaire de plus en plus fine de ces canaux et de leurs sous-unités régulatrices, ainsi que la démonstration de leur implication dans les processus nociceptifs, a permis de définitivement considérer ces structures comme des cibles pharmacologiques de premier choix pour le traitement de la douleur. La recherche d’inhibiteurs spécifiques des canaux calciques dépendants du voltage laisse ainsi entrevoir le développement de nouvelles molécules analgésiques fortement prometteuses.
Summary
Voltage-dependent calcium channels represent a major pathway of calcium entry into neurons, where they participate actively to cell excitability and to the molecular processes of synaptic transmission. For that reason, they have been the direct or indirect pharmacological targets of analgesics and this long before their implication in the physiology of nociception had been demonstrated. These last years, the still more refined molecular characterization of these channels and their associated regulatory subunits and the demonstration of their implication in nociceptive processes indicates that these structures are prime pharmacological targets for the management of pain. Herein, we detail the recent breakthroughs on calcium channel structure, function and pharmacology, review the implication of calcium channels in the transmission of nociception, and evaluate their importance as targets for the treatment of pain perception. The search for specific inhibitors of voltage-dependent calcium channels appears as a prelude to the development of new promising analgesic molecules.
Parties annexes
Références
- 1. Craig AD. A new view of pain as a homeostatic emotion. Trends Neurosci 2003 ; 26 : 303-7.
- 2. Julius D, Basbaum AI. Molecular mechanisms of nociception. Nature 2001 ; 413 : 203-10.
- 3. Craig AD. Pain mechanisms : labeled lines versus convergence in central processing. Annu Rev Neurosci 2003 ; 26 : 1-30.
- 4. McCleskey EW, Gold MS. Ion channels of nociception. Annu Rev Physiol 1999 ; 61 : 835-56.
- 5. Meir A, Ginsburg S, Butkevich A, et al. Ion channels in presynaptic nerve terminals and control of transmitter release. Physiol Rev 1999 ; 79 : 1019-88.
- 6. Ertel EA, Campbell KP, Harpold MM, et al. Nomenclature of voltage-gated calcium channels. Neuron 2000 ; 25 : 533-5.
- 7. Hatakeyama S, Wakamori M, Ino M, et al. Differential nociceptive responses in mice lacking the alpha(1B) subunit of N-type Ca2+ channels. Neuroreport 2001 ; 12 : 2423-7.
- 8. Saegusa H, Kurihara T, Zong S, et al. Suppression of inflammatory and neuropathic pain symptoms in mice lacking the N-type Ca2+ channel. EMBO J 2001 ; 20 : 2349-56.
- 9. Kerr LM, Yoshikami D. A venom peptide with a novel presynaptic blocking action. Nature 1984 ; 308 : 282-4.
- 10. Olivera BM, Cruz LJ, de Santos V, et al. Neuronal calcium channel antagonists. Discrimination between calcium channel subtypes using omega-conotoxin from Conus magus venom. Biochemistry 1987 ; 26 : 2086-90.
- 11. Malmberg AB, Yaksh TL. Effect of continuous intrathecal infusion of omega-conopeptides, N-type calcium-channel blockers, on behavior and antinociception in the formalin and hot-plate tests in rats. Pain 1995 ; 60 : 83-90.
- 12. Chaplan SR, Pogrel JW, Yaksh TL. Role of voltage-dependent calcium channel subtypes in experimental tactile allodynia. J Pharmacol Exp Ther 1994 ; 269 : 1117-23.
- 13. Staats PS, Yearwood T, Charapata SG, et al. Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS : a randomized controlled trial. JAMA 2004 ; 291 : 63-70.
- 14. Penn RD, Paice JA. Adverse effects associated with the intrathecal administration of ziconotide. Pain 2000 ; 85 : 291-6.
- 15. Adams DJ, Smith AB, Schroeder CI, et al. Omega-conotoxin CVID inhibits a pharmacologically distinct voltage-sensitive calcium channel associated with transmitter release from preganglionic nerve terminals. J Biol Chem 2003 ; 278 : 4057-62.
- 16. Smith MT, Cabot PJ, Ross FB, et al. The novel N-type calcium channel blocker, AM336, produces potent dose-dependent antinociception after intrathecal dosing in rats and inhibits substance P release in rat spinal cord slices. Pain 2002 ; 96 : 119-27.
- 17. Blake DW, Scott DA, Angus JA, Wright CE. Synergy between intrathecal omega-conotoxin CVID and dexmedetomidine to attenuate mechanical hypersensitivity in the rat. Eur J Pharmacol 2005 ; 506 : 221-7.
- 18. Seko T, Kato M, Kohno H, et al. Structure-activity study of L-cysteine-based N-type calcium channel blockers : optimization of N- and C-terminal substituents. Bioorg Med Chem Lett 2002 ; 12 : 915-8.
- 19. Teodori E, Baldi E, Dei S, et al. Design, synthesis, and preliminary pharmacological evaluation of 4-aminopiperidine derivatives as N-type calcium channel blockers active on pain and neuropathic pain. J Med Chem 2004 ; 47 : 6070-81.
- 20. Bell TJ, Thaler C, Castiglioni AJ, et al. Cell-specific alternative splicing increases calcium channel current density in the pain pathway. Neuron 2004 ; 41 : 127-38.
- 21. Seward E, Hammond C, Henderson G. Mu-opioid-receptor-mediated inhibition of the N-type calcium-channel current. Proc Biol Sci 1991 ; 244 : 129-35.
- 22. De Waard M, Liu H, Walker D, et al. Direct binding of G-protein betagamma complex to voltage-dependent calcium channels. Nature 1997 ; 385 : 446-50.
- 23. Zamponi GW, Bourinet E, Nelson D, et al. Crosstalk between G proteins and protein kinase C mediated by the calcium channel alpha1 subunit. Nature 1997 ; 385 : 442-6.
- 24. Marker CL, Lujan R, Loh HH, Wickman K. Spinal G-protein-gated potassium channels contribute in a dose-dependent manner to the analgesic effect of mu- and delta- but not kappa-opioids. J Neurosci 2005 ; 25 : 3551-9.
- 25. Wise A, Gearing K, Rees S. Target validation of G-protein coupled receptors. Drug Discov Today 2002 ; 7 : 235-46.
- 26. Meunier JC. Nociceptin/orphanin FQ and the opioid receptor-like ORL1 receptor. Eur J Pharmacol 1997 ; 340 : 1-15.
- 27. Beedle AM, McRory JE, Poirot O, et al. Agonist-independent modulation of N-type calcium channels by ORL1 receptors. Nat Neurosci 2004 ; 7 : 118-25.
- 28. Ophoff RA, Terwindt GM, Vergouwe MN, et al. Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell 1996 ; 87 : 543-52.
- 29. Pietrobon D, Striessnig J. Neurobiology of migraine. Nat Rev Neurosci 2003 ; 4 : 386-98.
- 30. Yokoyama K, Kurihara T, Saegusa H, et al. Blocking the R-type (Cav2.3) Ca2+ channel enhanced morphine analgesia and reduced morphine tolerance. Eur J Neurosci 2004 ; 20 : 3516-9.
- 31. Saegusa H, Kurihara T, Zong S, et al. Altered pain responses in mice lacking alpha 1E subunit of the voltage-dependent Ca2+ channel. Proc Natl Acad Sci USA 2000 ; 97 : 6132-7.
- 32. Todorovic SM, Pathirathna S, Meyenburg A, Jevtovic-Todorovic V. Mechanical and thermal anti-nociception in rats after systemic administration of verapamil. Neurosci Lett 2004 ; 360 : 57-60.
- 33. Murakami M, Fleischmann B, De Felipe C, et al. Pain perception in mice lacking the beta3 subunit of voltage-activated calcium channels. J Biol Chem 2002 ; 277 : 40342-51.
- 34. Bichet D, Cornet V, Geib S, et al. The I-II loop of the Ca2+ channel alpha1 subunit contains an endoplasmic reticulum retention signal antagonized by the beta subunit. Neuron 2000 ; 25 : 177-90.
- 35. Cuchillo-Ibanez I, Aldea M, Brocard J, et al. Inhibition of voltage-gated calcium channels by sequestration of beta subunits. Biochem Biophys Res Commun 2003 ; 311 : 1000-7.
- 36. Newton RA, Bingham S, Case PC, et al. Dorsal root ganglion neurons show increased expression of the calcium channel alpha2delta-1 subunit following partial sciatic nerve injury. Brain Res Mol Brain Res 2001 ; 95 : 1-8.
- 37. Luo ZD, Chaplan SR, Higuera ES, et al. Upregulation of dorsal root ganglion (alpha)2(delta) calcium channel subunit and its correlation with allodynia in spinal nerve-injured rats. J Neurosci 2001 ; 21 : 1868-75.
- 38. Li CY, Song YH, Higuera ES, Luo ZD. Spinal dorsal horn calcium channel alpha2delta-1 subunit upregulation contributes to peripheral nerve injury-induced tactile allodynia. J Neurosci 2004 ; 24 : 8494-9.
- 39. Todorovic SM, Meyenburg A, Jevtovic-Todorovic V. Mechanical and thermal antinociception in rats following systemic administration of mibefradil, a T-type calcium channel blocker. Brain Res 2002 ; 951 : 336-40.
- 40. Dogrul A, Gardell LR, Ossipov MH, et al. Reversal of experimental neuropathic pain by T-type calcium channel blockers. Pain 2003 ; 105 : 159-68.
- 41. Flatters SJ, Bennett GJ. Ethosuximide reverses paclitaxel- and vincristine-induced painful peripheral neuropathy. Pain 2004 ; 109 : 150-61.
- 42. Todorovic SM, Pathirathna S, Brimelow BC, et al. 5beta-reduced neuroactive steroids are novel voltage-dependent blockers of T-type Ca2+ channels in rat sensory neurons in vitro and potent peripheral analgesics in vivo. Mol Pharmacol 2004 ; 66 : 1223-35.
- 43. Todorovic SM, Meyenburg A, Jevtovic-Todorovic V. Redox modulation of peripheral T-type Ca2+ channels in vivo : alteration of nerve injury-induced thermal hyperalgesia. Pain 2004 ; 109 : 328-39.
- 44. Bourinet E, Alloui A, Monteil A, et al. Silencing of the Ca(v)3.2 T-type calcium channel gene in sensory neurons demonstrates its major role in nociception. EMBO J 2005 ; 24 : 315-24.
- 45. Burian M, Geisslinger G. COX-dependent mechanisms involved in the antinociceptive action of NSAIDs at central and peripheral sites. Pharmacol Ther 2005 ; 107 : 139-54.
- 46. Coluzzi F, Mattia C. Mechanism-based treatment in chronic neuropathic pain : the role of antidepressants. Curr Pharm Des 2005 ; 11 : 2945-60.
- 47. Eglen RM, Hunter JC, Dray A. Ions in the fire : recent ion-channel research and approaches to pain therapy. Trends Pharmacol Sci 1999 ; 20 : 337-42.
- 48. Jarvis MF, Burgard EC, McGaraughty S, et al. A-317491, a novel potent and selective non-nucleotide antagonist of P2X3 and P2X2/3 receptors, reduces chronic inflammatory and neuropathic pain in the rat. Proc Natl Acad Sci USA 2002 ; 99 : 17179-84.
- 49. Vyklicky L, Knotkova-Urbancova H, Vitaskova Z, et al. Inflammatory mediators at acidic pH activate capsaicin receptors in cultured sensory neurons from newborn rats. J Neurophysiol 1998 ; 79 : 670-6.
- 50. Voilley N. Acid-sensing ion channels (ASICs) : new targets for the analgesic effects of non-steroid anti-inflammatory drugs (NSAIDs). Curr Drug Targets Inflamm Allergy 2004 ; 3 : 71-9.
- 51. Wilson JA, Garry EM, Anderson HA, et al. NMDA receptor antagonist treatment at the time of nerve injury prevents injury-induced changes in spinal NR1 and NR2B subunit expression and increases the sensitivity of residual pain behaviours to subsequently administered NMDA receptor antagonists. Pain 2005 ; 117 : 421-32.
- 52. Lossignol DA, Obiols-Portis M, Body JJ. Successful use of ketamine for intractable cancer pain. Support Care Cancer 2005 ; 13 : 188-93.