Українська English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

(English title: Physiological Journal)

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2013; 59(2): 104-110

P2x3-receptor desensitization as an alternative mechanism of analgesia

Petrenko NS, Kryshtal' OO

    O.O. Bogomoletz Institute of Physiology National Academy of Science of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz59.02.104


Abstract

One of the most important current medical problems is the synthesis of substances that could suppress pathological pain. It has not been yet invented any method for chronic pain inhibition. Chronic pain is largely mediated by the activation of purinergic P2X3- and P2X2/3-receptors. They are expressed in nociceptive sensory neurons and are the prospective targets for analgesic drugs. There are several potential strategies to prevent P2X3 receptor activation. Recent studies have shown that P2X3-receptor antagonists and genetic deletion may have analgesic effects in inflammatory and neuropathic models. P2X3-receptors have fast and persistent desensitization. By influencing this property it could serve to reduce the ATP-mediated sensation of chronic pain. Therefore, in this review we outline and analyze the effectiveness and prospects of pharmacological agents acting through desensitization of P2X3-receptor versus its competitive antagonists.

Keywords: Р2Х3-receptor, chronic pain, antagonists,desensitization.

Full text: (PDF, in Ukrainian)

References

  1. Abbracchio M.P., Burnstock G., Verkhratsky A., Zimmermann H. Purinergic signalling in the nervous system: an overview . Trends Neurosci. 2009. N 32. P.19-29. CrossRef PubMed
    2.  
  2. Barclay J., Patel S., Dorn G., Wotherspoon G., Moffatt S., Eunson L., Abdel'al S., Natt F., Hall J., Winter J., Bevan S., Wishart W., Fox A., Ganju P. Functional downregulation of P2X3 receptor subunit in rat sensory neurons reveals a significant role in chronic neuropathic and inflammatory pain . J.Neurosci. 2002. N 22. P.8139-8147. CrossRef PubMed
    3.  
  3. Bradbury E.J., Burnstock G., McMahon S.B. The expression of P2X3 purinoreceptors in sensory neurons: effects of axotomy and glial-derived neurotrophic factor . Mol.Cell Neurosci. 1998. N 12. P.256-268. CrossRef PubMed
    4.  
  4. Brandes J.L., Kudrow D., Stark S.R., O'Carroll C.P., Adelman J.U., O'Donnell F.J., Alexander W.J., Spruill S.E., Barrett P.S., Lener S.E. Sumatriptan-naproxen for acute treatment of migraine: a randomized trial . JAMA. 2007. N 297. P.1443-1454. CrossRef
    5.  
  5. Browne L.E., Jiang L.H., North R.A. New structure enlivens interest in P2X receptors . Trends Pharmacol. Sci. 2010. N 31. P.229-237. CrossRef PubMed PubMedCentral
    6.  
  6. Burgard E.C., Niforatos W., van'Biesen T., Lynch K.J., Kage K.L., Touma E., Kowaluk E.A., Jarvis M.F. Competitive antagonism of recombinant P2X(2/3) receptors by 2', 3'-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate (TNP-ATP) . Mol.Pharmacol. 2000. N 58. P.1502-1510. CrossRef PubMed
    7.  
  7. Burnstock G. P2X receptors in sensory neurones . Brit.J.Anaesth. 2000. N 84. P.476-488. CrossRef PubMed
    8.  
  8. Burnstock G. Purinergic P2 receptors as targets for novel analgesics . Pharmacol.Therap. 2006. N 110. P.433-454.
    9.  
  9. Burnstock G., Wood J.N. Purinergic receptors: their role in nociception and primary afferent neurotransmission . Curr.Opin.Neurobiol. 1996. N 6. P.526-532.  CrossRef.1016/S0959-4388(96)80060-2
    10.  
  10. Chizh B.A., Illes P. P2X receptors and nociception . Pharmacol.Rev. 2001. N 53. P.553-568.  PubMed
    11.  
  11. Chronicle E., Mulleners W. Anticonvulsant drugs for migraine prophylaxis . Cochrane.Database.Syst.Rev. 2004. P.CD003226. CrossRef
    12.  
  12. Cockayne D.A., Hamilton S.G., Zhu Q.M., Dunn P.M., Zhong Y., Novakovic S., Malmberg A.B., Cain G., Berson A., Kassotakis L., Hedley L., Lachnit W.G., Burnstock G., McMahon S.B., Ford A.P. Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice . Nature. 2000. N 407. P.1011-1015. CrossRef PubMed
    13.  
  13. Cook S.P., McCleskey E.W. Desensitization, recovery and Ca(2+)-dependent modulation of ATP-gated P2X receptors in nociceptors . Neuropharmacology. 1997. N 36. P.1303-1308. CrossRef.1016/S0028-3908(97)00132-9
    14.  
  14. Delicado E.G., Miras-Portugal M.T., Carrasquero L.M., Leon D., Perez-Sen R., Gualix J. Dinucleoside polyphosphates and their interaction with other nucleotide signaling pathways . Pflug. Arch. 2006. N 452. P.563-572.
    15.  
  15. Dorofeeva N.A., Barygin O.I., Staruschenko A., Bolshakov K.V., Magazanik L.G. Mechanisms of non-steroid anti-inflammatory drugs action on ASICs expressed in hippocampal interneurons . J.Neurochem. 2008. N 106. P.429-441. CrossRef PubMed
    16.  
  16. Duggan K.C., Walters M.J., Musee J., Harp J.M., Kiefer J.R., Oates J.A., Marnett L.J. Molecular basis for cyclooxygenase inhibition by the non-steroidal antiinflammatory drug naproxen . J.Biol.Chem. 2010. N 285. P.34950-34959. CrossRef PubMed PubMedCentral
    17.  
  17. Ford A.P. In pursuit of P2X3 antagonists: novel therapeutics for chronic pain and afferent sensitization . Purinergic.Signal. 2012. N 8. P.3-26. CrossRef PubMed PubMedCentral
    18.  
  18. Ford A.P., Cockayne D.A. ATP and P2X purinoceptors in urinary tract disorders . Handb.Exp.Pharmacol. 2011. P.485-526. CrossRef.1007/978-3-642-16499-6_22 PubMed
    19.  
  19. Gever J.R., Soto R., Henningsen R.A., Martin R.S., Hackos D.H., Panicker S., Rubas W., Oglesby I.B., Dillon M.P., Milla M.E., Burnstock G., Ford A.P. AF-353, a novel, potent and orally bioavailable P2X3/P2X2/3 receptor antagonist . Brit.J.Pharmacol. 2010. N 160. P.13871398.  CrossRef
    20.  
  20. Giniatullin R., Nistri A., Fabbretti E. Molecular mechanisms of sensitization of pain-transducing P2X3 receptors by the migraine mediators CGRP and NGF . Desensitizatsiya R2H3-retseptoriv yak al'ternativnii mehanizm anal'gezii ISSN 0201-8489 Fiziol. zhurn., 2013, T. 59, N 2 109 Mol.Neurobiol. 2008. N 37. P.83-90. 
    21.  
  21. Giniatullin R., Nistri A., Yakel J.L. Desensitization of nicotinic ACh receptors: shaping cholinergic signaling . Trends Neurosci. 2005. N 28. P.371-378. CrossRef PubMed
    22.  
  22. Grishin E.V., Savchenko G.A., Vassilevski A.A., Korolkova Y.V., Boychuk Y.A., Viatchenko-Karpinski V.Y., Nadezhdin K.D., Arseniev A.S., Pluzhnikov K.A., Kulyk V.B., Voitenko N.V., Krishtal O.O. Novel peptide from spider venom inhibits P2X3 receptors and inflammatory pain . Ann.Neurol. 2010. N 67. P.680-683. PubMed
    23.  
  23. Hausmann R., Rettinger J., Gerevich Z., Meis S., Kassack M.U., Illes P., Lambrecht G., Schmalzing G. The suramin analog 4,4',4'',4'''-(carbonylbis(imino-5,1,3benzenetriylbis (carbonylimino)tetra-kis-benzenesulfonic acid (NF110) potently blocks P2X3 receptors: subtype selectivity is determined by location of sulfonic acid groups . Mol.Pharmacol. 2006. N 69. P.2058-2067. CrossRef PubMed
    24.  
  24. Hautaniemi T., Petrenko N., Skorinkin A., Giniatullin R. The inhibitory action of the antimigraine nonsteroidal antiinflammatory drug naproxen on P2X3 receptor-mediated responses in rat trigeminal neurons . Neuroscience. 2012. N 209. P.32-38. CrossRef PubMed
    25.  
  25. Honore P., Kage K., Mikusa J., Watt A.T., Johnston J.F., Wyatt J.R., Faltynek P.R., Jarvis M.F., Lynch K. Analgesic profile of intrathecal P2X(3) antisense oligonucleotide treatment in chronic inflammatory and neuropathic pain states in rats . Pain. 2002. N 99. P.11-19. CrossRef.1016/S0304-3959(02)00032-5
    26.  
  26. Jarvis M.F., Burgard E.C., McGaraughty S., Honore P., Lynch K., Brennan T.J., Subieta A., van Biesen T., Cartmell J., Bianchi B., Niforatos W., Kage K., Yu H., Mikusa J., Wismer C.T., Zhu C.Z., Chu K., Lee C.H., Stewart A.O., Polakowski J., Cox B.F., Kowaluk E., Williams M., Sullivan J., Faltynek C. 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.U.S.A. 2002. N 99. P.17179-17184. CrossRef PubMed PubMedCentral
    27.  
  27. Kabanova N.V., Vassilevski A.A., Rogachevskaja O.A., Bystrova M.F., Korolkova Y.V., Pluzhnikov K.A., Romanov R.A., Grishin E.V., Kolesnikov S.S. Modulation of P2X3 receptors by spider toxins . Biochim.and Biophys.Acta. 2012. N 1818. P.2868-2875.
    28.  
  28. Kawate T., Michel J.C., Birdsong W.T., Gouaux E. Crystal structure of the ATP-gated P2X(4) ion channel in the closed state . Nature. 2009. N 460. P.592-598. CrossRef PubMed PubMedCentral
    29.  
  29. Kennedy C. P2X receptors: targets for novel analgesics? . Neuroscientist. 2005. N 11. P.345-356.  CrossRef PubMed
    30.  
  30. Kennedy C., Assis T.S., Currie A.J., Rowan E.G. Crossing the pain barrier: P2 receptors as targets for novel analgesics . J.Physiol. 2003. N 553. P.683-694.  CrossRef PubMed PubMedCentral
    31.  
  31. Kennedy C. Leff P. Painful connection for ATP . Nature. 1995. N 377. P.385-386. CrossRef PubMed
    32.  
  32. Khakh B.S. North R.A. P2X receptors as cell-surface ATP sensors in health and disease . Ibid. 2006. N 442. P.527-532.
    33.  
  33. Krishtal O.A., Marchenko S.M., Pidoplichko V.I. Receptor for ATP in the membrane of mammalian sensory neurones . Neurosci.Lett. 1983. N 35. P.41-45. CrossRef.1016/0304-3940(83)90524-4
    34.  
  34. Lee C.H., Perner R.J., Larson D.P., Koenig J.R., Gomtsyan A.R., Zheng G.Z., Didomenico Stewart A.O., Bayburt E.K. Abbott Laboratories. Preparation of trisubstituted N-[(1S)-1,2,3,4-tetrahydro-1-naphthalenyl] benzamides as inhibitors of P2X3 and P2X2/P2X3 containing receptors for treating pain, urinary incontinence and bladder overactivity . 2002. Patent 129513-93-5.
    35.  
  35. McLennan A. Ap4A and Other Dinucleoside Polyphosphates . Boca Raton, FL: CRC Press Inc, 1992. 368 p.
    36.  
  36. Melnik S., Wright M., Tanner J.A., Tsintsadze T., Tsintsadze V., Miller A.D., Lozovaya N. Diadenosine polyphosphate analog controls postsynaptic excitation in CA3-CA1 synapses via a nitric oxide-dependent mechanism . J.Pharmacol.Exp.Therap. 2006. N 318. P.579-588.
    37.  
  37. Millan M.J. Descending control of pain . Prog.Neurobiol. 2002. N 66. P.355-474. CrossRef.1016/S0301-0082(02)00009-6
    38.  
  38. Miras-Portugal M.T., Gualix J., Pintor J. The neurotransmitter role of diadenosine polyphosphates . FEBS Lett. 1998. N 430. P.78-82. CrossRef.1016/S0014-5793(98)00560-2
    39.  
  39. Nakagawa T., Wakamatsu K., Zhang N., Maeda S., Minami M., Satoh M., Kaneko S. Intrathecal administration of ATP produces long-lasting allodynia in rats: differential mechanisms in the phase of the induction and maintenance . Neuroscience. 2007. N 147. P.445-455.  CrossRef PubMed
    40.  
  40. North R.A. Molecular physiology of P2X receptors . Physiol Rev. 2002. N 82. P.1013-1067.  CrossRef PubMed
    41.  
  41. North R.A. P2X3 receptors and peripheral pain mechanisms . J.Physiol. 2004. N 554. P.301-308. CrossRef PubMed PubMedCentral
    42.  
  42. North R.,A. Surprenant A. Pharmacology of cloned P2X receptors . Annu.Rev.Pharmacol.Toxicol. 2000. N 40. P.563-580. CrossRef PubMed
    43.  
  43. Pintor J., Diaz-Hernandez M., Gualix J., Gomez-Villafuertes R., Hernando F., Miras-Portugal M.T. Diadenosine polyphosphate receptors. from rat and guinea-pig brain to human nervous system . Pharmacol. Therap. 2000. N 87. P.103-115.
    44.  
  44. Pintor J., Diaz-Rey M.A., Torres M., Miras-Portugal M.T. Presence of diadenosine polyphosphates Ap4A and Ap5A in rat brain synaptic terminals. Ca2+ dependent release evoked by 4-aminopyridine and veratridine . Neurosci. Lett. 1992. N 136. P.141-144. CrossRef.1016/0304-3940(92)90034-5
    45.  
  45. Pratt E.B., Brink T.S., Bergson P., Voigt M.M., Cook S.P. Use-dependent inhibition of P2X3 receptors by nanomolar agonist . J.Neurosci. 2005. N 25. P.7359-7365. CrossRef PubMed
    46.  
  46. Sokolova E., Nistri A., Giniatullin R. Negative cross talk between anionic GABAA and cationic P2X ionotropic receptors of rat dorsal root ganglion neurons . Ibid. 2001. N 21. P.4958-4968.
    47.  
  47. Sokolova E., Skorinkin A., Fabbretti E., Masten L., Nistri A., Giniatullin R. Agonist-dependence of recovery from desensitization of P2X(3) receptors provides a novel and sensitive approach for their rapid up or downregulation . Brit. J.Pharmacol. 2004. N 141. P.1048-1058. CrossRef PubMed PubMedCentral
    48.  
  48. Sokolova E., Skorinkin A., Moiseev I., Agrachev A., Nistri N.S. Petrenko, O.O. Krishtal' 110 ISSN 0201-8489 Fiziol. zhurn., 2013, T. 59, N 2 A., Giniatullin R. Experimental and modeling studies of desensitization of P2X3 receptors . Mol.Pharmacol. 2006. N 70. P.373-382.
    49.  
  49. Souslova V., Cesare P., Ding Y., Akopian A. N., Stanfa L., Suzuki R., Carpenter K., Dickenson A., Boyce S., Hill R., Nebenuis-Oosthuizen D., Smith A. J., Kidd E. J., Wood J. N. Warm-coding deficits and aberrant inflammatory pain in mice lacking P2X3 receptors . Nature. 2000. N 407. P.1015-1017.  CrossRef PubMed
    50.  
  50. Trang T., Beggs S., Salter M.W. ATP receptors gate microglia signaling in neuropathic pain . Exp.Neurol. 2012. N 234. P.354-361.  CrossRef PubMed PubMedCentral
    51.  
  51. Servellen G., Heise B.A., Ellis R. Factors associated with antidepressant medication adherence and adherenceenhancement programmes: a systematic literature review . Ment.Health Fam.Med. 2011. N 8. P.255-271. PubMed PubMedCentral
    52.  
  52. Virginio C., Robertson G., Surprenant A., North R.A. Trinitrophenyl-substituted nucleotides are potent antagonists selective for P2X1, P2X3, and heteromeric P2X2/3 receptors . Mol.Pharmacol. 1998. N 53. P.969-973. PubMed
    53.  
  53. Voilley N., de'Weille J., Mamet J., Lazdunski M. Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acidsensing ion channels in nociceptors . J.Neurosci. 2001. N 21. P.8026-8033. CrossRef PubMed
© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2025.