Purinergic mechanosensory transduction and visceral pain

Molecular Pain

Volumn 5, Issue , 2009, Pages

  Burnstock, Geoffrey ^a  

^a ROYAL FREE AND UNIVERSITY COLLEGE MEDICAL SCHOOL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

PURINERGIC P2 RECEPTOR; PURINERGIC P2X3 RECEPTOR;

ANIMAL; BIOLOGICAL MODEL; DRUG ANTAGONISM; DRUG EFFECT; HUMAN; INNERVATION; MECHANOTRANSDUCTION; METABOLISM; PAIN; PATHOPHYSIOLOGY; PHYSIOLOGY; REVIEW; VISCERA;

ANIMALS; HUMANS; MECHANOTRANSDUCTION, CELLULAR; MODELS, BIOLOGICAL; PAIN; RECEPTORS, PURINERGIC P2; VISCERA;

EID: 75549091052     PISSN: None     EISSN: 17448069     Source Type: Journal    
DOI: 10.1186/1744-8069-5-69     Document Type: Review

References (115)

1. Bueno L. Gastrointestinal pharmacology: irritable bowel syndrome. Curr Opin Pharmacol 2005, 5:583-588. 10.1016/j.coph.2005.06.006, 16188501.
2. Kraneveld AD, Rijnierse A, Nijkamp FP, Garssen J. Neuro-immune interactions in inflammatory bowel disease and irritable bowel syndrome: future therapeutic targets. Eur J Pharmacol 2008, 585:361-374. 10.1016/j.ejphar.2008.02.095, 18417115.
3. Chen CC, Akopian AN, Sivilotti L, Colquhoun D, Burnstock G, Wood JN. A P2X purinoceptor expressed by a subset of sensory neurons. Nature 1995, 377:428-431. 10.1038/377428a0, 7566119.
4. Lewis C, Neidhart S, Holy C, North RA, Buell G, Surprenant A. Coexpression of P2X2 and P2X3 receptor subunits can account for ATP-gated currents in sensory neurons. Nature 1995, 377:432-435. 10.1038/377432a0, 7566120.
5. Burnstock G. Release of vasoactive substances from endothelial cells by shear stress and purinergic mechanosensory transduction. J Anat 1999, 194:335-342. 10.1046/j.1469-7580.1999.19430335.x, 1467933, 10386771.
6. Ferguson DR, Kennedy I, Burton TJ. ATP is released from rabbit urinary bladder epithelial cells by hydrostatic pressure changes - a possible sensory mechanism?. J Physiol 1997, 505:503-511. 10.1111/j.1469-7793.1997.503bb.x, 1160080, 9423189.
7. Namasivayam S, Eardley I, Morrison JFB. Purinergic sensory neurotransmission in the urinary bladder: an in vitro study in the rat. BJU Int 1999, 84:854-860. 10.1046/j.1464-410x.1999.00310.x, 10532986.
8. Cockayne DA, Hamilton SG, Zhu Q-M, Dunn PM, Zhong Y, Novakovic S, Malmberg AB, Cain G, Berson A, Kassotakis L, Hedley L, Lachnit WG, Burnstock G, McMahon SB, Ford APDW. Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice. Nature 2000, 407:1011-1015. 10.1038/35039519, 11069181.
9. Cockayne DA, Dunn PM, Zhong Y, Hamilton SG, Cain GR, Knight G, Ruan H-Z, Ping Y, Nunn P, Bei M, McMahon SB, Burnstock G, Ford APDW. P2X2 knockout mice and P2X2/P2X3 double knockout mice reveal a role for the P2X2 receptor subunit in mediating multiple sensory effects of ATP. J Physiol 2005, 567:621-639. 10.1113/jphysiol.2005.088435, 1474198, 15961431.
10. Vlaskovska M, Kasakov L, Rong W, Bodin P, Bardini M, Cockayne DA, Ford APDW, Burnstock G. P2X3 knockout mice reveal a major sensory role for urothelially released ATP. J Neurosci 2001, 21:5670-5677.
11. Zhong Y, Banning AS, Cockayne DA, Ford APDW, Burnstock G, McMahon SB. Bladder and cutaneous sensory neurons of the rat express different functional P2X receptors. Neuroscience 2003, 120:667-675. 10.1016/S0306-4522(03)00243-4, 12895508.
12. Xu L, Gebhart GF. Characterization of mouse lumbar splanchnic and pelvic nerve urinary bladder mechanosensory afferents. J Neurophysiol 2008, 99:244-253. 10.1152/jn.01049.2007, 2659401, 18003875.
13. Rong W, Spyer M, Burnstock G. Activation and sensitisation of low and high threshold afferent fibres mediated by P2X receptors in the mouse urinary bladder. J Physiol 2002, 541:591-600. 10.1113/jphysiol.2001.013469, 2290323, 12042363.
14. Lazzeri M. The physiological function of the urothelium - more than a simple barrier. Urol Int 2006, 76:289-295. 10.1159/000092049, 16679827.
15. Sui GP, Wu C, Fry CH. Characterization of the purinergic receptor subtype on guinea-pig suburothelial myofibroblasts. BJU Int 2006, 97:1327-1331. 10.1111/j.1464-410X.2006.06200.x, 16686733.
16. de Groat WC. Integrative control of the lower urinary tract: preclinical perspective. Br J Pharmacol 2006, 147(Suppl 2):S25-S40. 10.1038/sj.bjp.0706604, 1751498, 16465182.
17. Birder LA, Barrick SR, Roppolo JR, Kanai AJ, de Groat WC, Kiss S, Buffington CA. Feline interstitial cystitis results in mechanical hypersensitivity and altered ATP release from bladder urothelium. Am J Physiol Renal Physiol 2003, 285:F423-F429.
18. Du S, Araki I, Mikami Y, Zakoji H, Beppu M, Yoshiyama M, Takeda M. Amiloride-sensitive ion channels in urinary bladder epithelium involved in mechanosensory transduction by modulating stretch-evoked adenosine triphosphate release. Urology 2007, 69:590-595. 10.1016/j.urology.2007.01.039, 17382185.
19. Matsumoto-Miyai K, Kagase A, Murakawa Y, Momota Y, Kawatani M. Extracellular Ca2+ regulates the stimulus-elicited ATP release from urothelium. Auton Neurosci 2009, 150:94-99. 10.1016/j.autneu.2009.05.253, 19525154.
20. Pandita RK, Andersson KE. Intravesical adenosine triphosphate stimulates the micturition reflex in awake, freely moving rats. J Urol 2002, 168:1230-1234. 10.1016/S0022-5347(05)64631-9, 12187273.
21. Brady CM, Apostolidis A, Yiangou Y, Baecker PA, Ford AP, Freeman A, Jacques TS, Fowler CJ, Anand P. P2X3-immunoreactive nerve fibres in neurogenic detrusor overactivity and the effect of intravesical resiniferatoxin. Eur Urol 2004, 46:247-253. 10.1016/j.eururo.2003.12.017, 15245821.
22. Hu ST, Gever J, Nunn PA, Ford AP, Zhu Q-M. Cystometric studies with ATP, PPADS and TNP-ATP in conscious and anaesthetised C57BL/6 mice. J Urol 2004, 171:461-462.
23. King BF, Knowles I, Burnstock G, Ramage A. Investigation of the effects of P2 purinoceptor ligands on the micturition reflex in female urethane-anaesthetised rats. Br J Pharmacol 2004, 142:519-530. 10.1038/sj.bjp.0705790, 1574961, 15148261.
24. Birder LA, Nakamura Y, Kiss S, Nealen ML, Barrick S, Kanai AJ, Wang E, Ruiz G, de Groat WC, Apodaca G, Watkins S, Caterina MJ. Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1. Nat Neurosci 2002, 5:856-860. 10.1038/nn902, 12161756.
25. Daly D, Rong W, Chess-Williams R, Chapple C, Grundy D. Bladder afferent sensitivity in wild-type and TRPV1 knockout mice. J Physiol 2007, 583:663-674. 10.1113/jphysiol.2007.139147, 2277033, 17627983.
26. Zagorodnyuk VP, Gibbins IL, Costa M, Brookes SJ, Gregory SJ. Properties of the major classes of mechanoreceptors in the guinea pig bladder. J Physiol 2007, 585:147-163. 10.1113/jphysiol.2007.140244, 2375472, 17916614.
27. Zagorodnyuk VP, Brookes SJ, Spencer NJ, Gregory S. Mechanotransduction and chemosensitivity of two major classes of bladder afferents with endings in the vicinity to the urothelium. J Physiol 2009, 587:3523-3538. 10.1113/jphysiol.2009.172577, 19470774.
28. Kim JC, Yoo JS, Park EY, Hong SH, Seo SI, Hwang TK. Muscarinic and purinergic receptor expression in the urothelium of rats with detrusor overactivity induced by bladder outlet obstruction. BJU Int 2008, 101:371-375. 10.1111/j.1464-410X.2007.07251.x, 17922866.
29. Dang K, Lamb K, Cohen M, Bielefeldt K, Gebhart GF. Cyclophosphamide-induced bladder inflammation sensitizes and enhances P2X receptor function in rat bladder sensory neurons. J Neurophysiol 2008, 99:49-59. 10.1152/jn.00211.2007, 2659400, 17959738.
30. Smith CP, Vemulakonda VM, Kiss S, Boone TB, Somogyi GT. Enhanced ATP release from rat bladder urothelium during chronic bladder inflammation: effect of botulinum toxin A. Neurochem Int 2005, 47:291-297. 10.1016/j.neuint.2005.04.021, 15970360.
31. Mackenzie I, Burnstock G, Dolly JO. The effects of purified botulinum neurotoxin type A on cholinergic, adrenergic and non-adrenergic, atropine-resistant autonomic neuromuscular transmission. Neuroscience 1982, 7:997-1006. 10.1016/0306-4522(82)90056-2, 6124898.
32. Lee HY, Bardini M, Burnstock G. Distribution of P2X receptors in the urinary bladder and the ureter of the rat. J Urol 2000, 163:2002-2007. 10.1016/S0022-5347(05)67618-5, 10799247.
33. Rong W, Burnstock G. Activation of ureter nociceptors by exogenous and endogenous ATP in guinea pig. Neuropharmacology 2004, 47:1093-1101. 10.1016/j.neuropharm.2004.08.003, 15555643.
34. Knight GE, Bodin P, de Groat WC, Burnstock G. ATP is released from guinea pig ureter epithelium on distension. Am J Physiol Renal Physiol 2002, 282:F281-F288.
35. Calvert RC, Thompson CS, Burnstock G. ATP release from the human ureter on distension and P2X3 receptor expression on suburothelial sensory nerves. Purinergic Signalling 2008, 4:377-381. 10.1007/s11302-008-9123-1, 2583211, 18819020.
36. Risholm L. Studies on renal colic and its treatment by posterior splanchnic block. Acta Chir Scand 1954, 184(Suppl):5-64.
37. Canda AE, Turna B, Cinar GM, Nazli O. Physiology and pharmacology of the human ureter: basis for current and future treatments. Urol Int 2007, 78:289-298. 10.1159/000100830, 17495484.
38. Burnstock G. Purinergic signalling in gut. Handbook of Experimental Pharmacology. Purinergic and Pyrimidinergic Signalling II - Cardiovascular, Respiratory, Immune, Metabolic and Gastrointestinal Tract Function 2001, 151/II:141-238. Berlin: Springer-Verlag, Abbracchio MP, Williams M.
39. Burnstock G. Purine-mediated signalling in pain and visceral perception. Trends Pharmacol Sci 2001, 22:182-188. 10.1016/S0165-6147(00)01643-6, 11282418.
40. Wynn G, Rong W, Xiang Z, Burnstock G. Purinergic mechanisms contribute to mechanosensory transduction in the rat colorectum. Gastroenterology 2003, 125:1398-1409. 10.1016/j.gastro.2003.07.008, 14598256.
41. Dezaki K, Tsumura T, Maeno E, Okada Y. Receptor-mediated facilitation of cell volume regulation by swelling-induced ATP release in human epithelial cells. Jpn J Physiol 2000, 50:235-241. 10.2170/jjphysiol.50.235, 10880880.
42. Wijk T, Tomassen SF, Houtsmuller AB, De Jonge HR, Tilly BC. Increased vesicle recycling in response to osmotic cell swelling. Cause and consequence of hypotonicity-provoked ATP release. J Biol Chem 2003, 278:40020-40025. 10.1074/jbc.M307603200, 12871943.
43. Barthó L, Lénárd LJ, Lázár Z, Maggi CA. Connections between P2 purinoceptors and capsaicin-sensitive afferents in the intestine and other tissues. Eur J Pharmacol 1999, 375:203-210. 10.1016/S0014-2999(99)00253-8, 10443576.
44. Wynn G, Burnstock G. Adenosine 5'-triphosphate and it's relationship with other mediators that activate pelvic afferent neurons in the rat colorectum. Purinergic Signalling 2006, 2:517-526. 10.1007/s11302-005-5305-2, 2104004, 18404489.
45. Lakshmi S, Joshi PG. Co-activation of P2Y2 receptor and TRPV channel by ATP: implications for ATP induced pain. Cell Mol Neurobiol 2005, 25:819-832. 10.1007/s10571-005-4936-8, 16133936.
46. Christianson JA, Bielefeldt K, Altier C, Cenac N, Davis BM, Gebhart GF, High KW, Kollarik M, Randich A, Undem B, Vergnolle N. Development, plasticity and modulation of visceral afferents. Brain Res Rev 2009, 60:171-186. 10.1016/j.brainresrev.2008.12.004, 19150371.
47. Sugiura T, Bielefeldt K, Gebhart GF. Mouse colon sensory neurons detect extracellular acidosis via TRPV1. Am J Physiol Cell Physiol 2007, 292:C1768-C1774. 10.1152/ajpcell.00440.2006, 17251322.
48. De Schepper HU, De Winter BY, Van Nassauw L, Timmermans JP, Herman AG, Pelckmans PA, De Man JG. TRPV1 receptors on unmyelinated C-fibres mediate colitis-induced sensitization of pelvic afferent nerve fibres in rats. J Physiol 2008, 586:5247-5258. 10.1113/jphysiol.2008.159731, 2652143, 18755744.
49. Malin SA, Christianson JA, Bielefeldt K, Davis BM. TPRV1 expression defines functionally distinct pelvic colon afferents. J Neurosci 2009, 29:743-752. 10.1523/JNEUROSCI.3791-08.2009, 19158300.
50. Ueda T, Yamada T, Ugawa S, Ishida Y, Shimada S. TRPV3, a thermosensitive channel is expressed in mouse distal colon epithelium. Biochem Biophys Res Commun 2009, 383:130-134. 10.1016/j.bbrc.2009.03.143, 19336223.
51. Mochizuki T, Sokabe T, Araki I, Fujishita K, Shibasaki K, Uchida K, Naruse K, Koizumi S, Takeda M, Tominaga M. The TRPV4 cation channel mediates stretch-evoked Ca2+ influx and ATP release in primary urothelial cell cultures. J Biol Chem 2009, 284:21257-21264. 10.1074/jbc.M109.020206, 19531473.
52. Brierley SM, Carter R, Jones W, Xu L, Robinson DR, Hicks GA, Gebhart GF, Blackshaw LA. Differential chemosensory function and receptor expression of splanchnic and pelvic colonic afferents in mice. J Physiol 2005, 567:267-281. 10.1113/jphysiol.2005.089714, 1474170, 15946967.
53. Page AJ, Martin CM, Blackshaw LA. Vagal mechanoreceptors and chemoreceptors in mouse stomach and esophagus. J Neurophysiol 2002, 87:2095-2103.
54. Page AJ, O'Donnell TA, Blackshaw LA. P2X purinoceptor-induced sensitization of ferret vagal mechanoreceptors in oesophageal inflammation. J Physiol 2000, 523:403-411. 10.1111/j.1469-7793.2000.00403.x, 2269809, 10699084.
55. Yu S, Undem BJ, Kollarik M. Vagal afferent nerves with nociceptive properties in guinea-pig oesophagus. J Physiol 2005, 563:831-842. 10.1113/jphysiol.2004.079574, 1665603, 15649987.
56. Ru F, Kollarik M. Adenosine activates a subset of nociceptive vagal sensory nerves in oesophagus [abstract]. Gastroenterology 2006, 130:A252.
57. Rao SS, Mudipalli RS, Mujica V, Utech CL, Zhao X, Conklin JL. An open-label trial of theophylline for functional chest pain. Dig Dis Sci 2002, 47:2763-2768. 10.1023/A:1021017524660, 12498299.
58. Winkler H, Westhead E. The molecular organization of adrenal chromaffin granules. Neuroscience 1980, 5:1803-1823. 10.1016/0306-4522(80)90031-7, 7432623.
59. Cooke HJ, Wunderlich J, Christofi FL. "The force be with you": ATP in gut mechanosensory transduction. News Physiol Sci 2003, 18:43-49.
60. Furuya K, Sokabe M, Furuya S. Characteristics of subepithelial fibroblasts as a mechano-sensor in the intestine: cell-shape-dependent ATP release and P2Y1 signaling. J Cell Sci 2005, 118:3289-3304. 10.1242/jcs.02453, 16030139.
61. Furuya S, Furuya K. Subepithelial fibroblasts in intestinal villi: roles in intercellular communication. Int Rev Cytol 2007, 264:165-223. full_text, 17964923.
62. Bertrand PP, Bornstein JC. ATP as a putative sensory mediator: activation of intrinsic sensory neurons of the myenteric plexus via P2X receptors. J Neurosci 2002, 22:4767-4775.
63. Castelucci P, Robbins HL, Poole DP, Furness JB. The distribution of purine P2X2 receptors in the guinea-pig enteric nervous system. Histochem Cell Biol 2002, 117:415-422. 10.1007/s00418-002-0404-4, 12029488.
64. Poole DP, Castelucci P, Robbins HL, Chiocchetti R, Furness JB. The distribution of P2X3 purine receptor subunits in the guinea pig enteric nervous system. Auton Neurosci 2002, 101:39-47. 10.1016/S1566-0702(02)00179-0, 12462358.
65. Bian X, Ren J, DeVries M, Schnegelsberg B, Cockayne DA, Ford AP, Galligan JJ. Peristalsis is impaired in the small intestine of mice lacking the P2X3 subunit. J Physiol 2003, 551:309-322. 10.1113/jphysiol.2003.044172, 2343160, 12813150.
66. Ren J, Bian X, DeVries M, Schnegelsberg B, Cockayne DA, Ford AP, Galligan JJ. P2X2 subunits contribute to fast synaptic excitation in myenteric neurons of the mouse small intestine. J Physiol 2003, 552:809-821. 10.1113/jphysiol.2003.047944, 2343442, 12937291.
67. Wynn G, Bei M, Ruan H-Z, Burnstock G. Purinergic component of mechanosensory transduction is increased in a rat model of colitis. Am J Physiol Gastrointest Liver Physiol 2004, 287:G647-G657. 10.1152/ajpgi.00020.2004, 15331354.
68. Shinoda M, Feng B, Gebhart GF. Peripheral and central P2X3 receptor contributions to colon mechanosensitivity and hypersensitivity in the mouse. Gastroenterology
69. Kirkup AJ, Brunsden AM, Grundy D. Receptors and transmission in the brain-gut axis: Potential for novel therapies. I. Receptors on visceral afferents. Am J Physiol Gastrointest Liver Physiol 2001, 280:G787-G794.
70. Holzer P. Gastrointestinal pain in functional bowel disorders: sensory neurons as novel drug targets. Expert Opin Ther Targets 2004, 8:107-123. 10.1517/14728222.8.2.107, 15102553.
71. Xu GY, Shenoy M, Winston JH, Mittal S, Pasricha PJ. P2X receptor-mediated visceral hyperalgesia in a rat model of chronic visceral hypersensitivity. Gut 2008, 57:1230-1237. 10.1136/gut.2007.134221, 18270243.
72. Zahn PK, Straub H, Wenk M, Pogatzki-Zahn EM. Adenosine A1 but not A2a receptor agonist reduces hyperalgesia caused by a surgical incision in rats: a pertussis toxin-sensitive G protein-dependent process. Anesthesiology 2007, 107:797-806. 10.1097/01.anes.0000286982.36342.3f, 18073555.
73. Knowles CH, Aziz Q. Visceral hypersensitivity in non-erosive reflux disease. Gut 2008, 57:674-683. 10.1136/gut.2007.127886, 18079285.
74. Banerjee B, Medda BK, Shaker R, Sengupta JN. TRPV1 and P2X3 expression in vagal and spinal pathways following acid-induced esophagitis in rats [abstract]. Gastroenterology 2006, 130:A133.
75. Brouns I, De Proost I, Pintelon I, Timmermans JP, Adriaensen D. Sensory receptors in the airways: neurochemical coding of smooth muscle-associated airway receptors and pulmonary neuroepithelial body innervation. Auton Neurosci 2006, 126-127:307-319. 10.1016/j.autneu.2006.02.006, 16600695.
76. Rich PB, Douillet CD, Mahler SA, Husain SA, Boucher RC. Adenosine triphosphate is released during injurious mechanical ventilation and contributes to lung edema. J Trauma 2003, 55:290-297. 10.1097/01.TA.0000078882.11919.AF, 12913640.
77. Brouns I, Van Genechten J, Burnstock G, Timmermans J-P, Adriaensen D. Ontogenesis of P2X3 receptor-expressing nerve fibres in the rat lung, with special reference to neuroepithelial bodies. Biomedical Research 2003, 14:80-86.
78. Kollarik M, Dinh QT, Fischer A, Undem BJ. Capsaicin-sensitive and -insensitive vagal bronchopulmonary C-fibres in the mouse. J Physiol 2003, 551:869-879. 10.1113/jphysiol.2003.042028, 2343302, 12909686.
79. Ruan T, Lin YS, Lin KS, Kou YR. Sensory transduction of pulmonary reactive oxygen species by capsaicin-sensitive vagal lung afferent fibres in rats. J Physiol 2005, 565:563-578. 10.1113/jphysiol.2005.086181, 1464522, 15802291.
80. Adriaensen D, Timmermans JP. Purinergic signalling in the lung: important in asthma and COPD?. Curr Opin Pharmacol 2004, 4:207-214. 10.1016/j.coph.2004.01.010, 15140410.
81. Lemaire I, Leduc N. Purinergic P2X7 receptor function in lung alveolar macrophages: pharmacologic characterisation and bidirectional regulation by Th1 and Th2 cytokines. Drug Dev Res 2004, 59:118-127.
82. Papka RE, Hafemeister J, Storey-Workley M. P2X receptors in the rat uterine cervix, lumbosacral dorsal root ganglia, and spinal cord during pregnancy. Cell Tissue Res 2005, 321:35-44. 10.1007/s00441-005-1114-8, 15902498.
83. Cook SP, Vulchanova L, Hargreaves KM, Elde R, McCleskey EW. Distinct ATP receptors on pain-sensing and stretch-sensing neurons. Nature 1997, 387:505-508. 10.1038/387505a0, 9168113.
84. Alavi AM, Dubyak GR, Burnstock G. Immunohistochemical evidence for ATP receptors in human dental pulp. J Dental Res 2001, 80:476-483.
85. Jiang J, Gu J. Expression of adenosine triphosphate P2X3 receptors in rat molar pulp and trigeminal ganglia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002, 94:622-626. 10.1067/moe.2002.128973, 12424458.
86. Renton T, Yiangou Y, Baecker PA, Ford AP, Anand P. Capsaicin receptor VR1 and ATP purinoceptor P2X3 in painful and nonpainful human tooth pulp. J Orofac Pain 2003, 17:245-250.
87. Hu B, Chiang CY, Hu JW, Dostrovsky JO, Sessle BJ. P2X receptors in trigeminal subnucleus caudalis modulate central sensitization in trigeminal subnucleus oralis. J Neurophysiol 2002, 88:1614-1624.
88. Bo X, Alavi A, Xiang Z, Oglesby I, Ford A, Burnstock G. Localization of ATP-gated P2X2 and P2X3 receptor immunoreactive nerves in rat taste buds. Neuroreport 1999, 10:1107-1111. 10.1097/00001756-199904060-00037, 10321492.
89. Rong W, Burnstock G, Spyer KM. P2X purinoceptor-mediated excitation of trigeminal lingual nerve terminals in an in vitro intra-arterially perfused rat tongue preparation. J Physiol 2000, 524:891-902. 10.1111/j.1469-7793.2000.00891.x, 2269894, 10790166.
90. Kataoka S, Toyono T, Seta Y, Ogura T, Toyoshima K. Expression of P2Y1 receptors in rat taste buds. Histochem Cell Biol 2004, 121:419-426. 10.1007/s00418-004-0647-3, 15103469.
91. Finger TE, Danilova V, Barrows J, Bartel DL, Vigers AJ, Stone L, Hellekant G, Kinnamon SC. ATP signaling is crucial for communication from taste buds to gustatory nerves. Science 2005, 310:1495-1499. 10.1126/science.1118435, 16322458.
92. Burnstock G. Purinergic P2 receptors as targets for novel analgesics. Pharmacol Therap 2006, 110:433-454.
93. Gever J, Cockayne DA, Dillon MP, Burnstock G, Ford APDW. Pharmacology of P2X channels. Pflugers Arch 2006, 452:513-537. 10.1007/s00424-006-0070-9, 16649055.
94. Gever JR, Rothschild S, Henningsen R, Martin R, Hackos D, Panicker S, Milla ME, Oglesby I, Dillon MP, Burnstock G, Ford APDW. RO-4, a novel, potent orally bioavailable P2X3/P2X2/3 antagonist. Br J Pharmacol 2009,
95. Carter DS, Alam M, Cai H, Dillon MP, Ford AP, Gever JR, Jahangir A, Lin C, Moore AG, Wagner PJ, Zhai Y. Identification and SAR of novel diaminopyrimidines. Part 1: The discovery of RO-4, a dual P2X3/P2X2/3 antagonist for the treatment of pain. Bioorg Med Chem Lett 2009, 19:1628-1631. 10.1016/j.bmcl.2009.02.003, 19231180.
96. Jahangir A, Alam M, Carter DS, Dillon MP, Bois DJ, Ford AP, Gever JR, Lin C, Wagner PJ, Zhai Y, Zira J. Identification and SAR of novel diaminopyrimidines. Part 2: The discovery of RO-51, a potent and selective, dual P2X3/P2X2/3 antagonist for the treatment of pain. Bioorg Med Chem Lett 2009, 19:1632-1635. 10.1016/j.bmcl.2009.01.097, 19231178.
97. Spelta V, Jiang LH, Surprenant A, North RA. Kinetics of antagonist actions at rat P2X2/3 heteromeric receptors. Br J Pharmacol 2002, 135:1524-1530. 10.1038/sj.bjp.0704591, 1573256, 11906966.
98. Liang SD, Gao Y, Xu CS, Xu BH, Mu SN. Effect of tetramethylpyrazine on acute nociception mediated by signaling of P2X receptor activation in rat. Brain Res 2004, 995:247-252. 10.1016/j.brainres.2003.09.070, 14672814.
99. 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, 22:8139-8147.
100. Honore P, Mikusa J, Bianchi B, McDonald H, Cartmell J, Faltynek C, Jarvis MF. TNP-ATP, a potent P2X3 receptor antagonist, blocks acetic acid-induced abdominal constriction in mice: comparison with reference analgesics. Pain 2002, 96:99-105. 10.1016/S0304-3959(01)00434-1, 11932066.
101. Stone LS, Vulchanova L. The pain of antisense: in vivo application of antisense oligonucleotides for functional genomics in pain and analgesia. Adv Drug Deliv Rev 2003, 55:1081-1112. 10.1016/S0169-409X(03)00105-4, 12935946.
102. Aoki Y, Ohtori S, Takahashi K, Ino H, Ozawa T, Douya H, Chiba T, Moriya H. P2X3-immunoreactive primary sensory neurons innervating lumbar intervertebral disc in rats. Brain Res 2003, 989:214-220. 10.1016/S0006-8993(03)03365-1, 14556943.
103. Hemmings-Mieszczak M, Dorn G, Natt FJ, Hall J, Wishart WL. Independent combinatorial effect of antisense oligonucleotides and RNAi-mediated specific inhibition of the recombinant rat P2X3 receptor. Nucleic Acids Res 2003, 31:2117-2126. 10.1093/nar/gkg322, 153750, 12682362.
104. Dorn G, Patel S, Wotherspoon G, Hemmings-Mieszczak M, Barclay J, Natt FJ, Martin P, Bevan S, Fox A, Ganju P, Wishart W, Hall J. siRNA relieves chronic neuropathic pain. Nucleic Acids Res 2004, 32:e49. 10.1093/nar/gnh044, 390346, 15026538.
105. Burnstock G, Wood JN. Purinergic receptors: their role in nociception and primary afferent neurotransmission. Curr Opin Neurobiol 1996, 6:526-532. 10.1016/S0959-4388(96)80060-2, 8794102.
106. Burnstock G. P2X receptors in sensory neurones. Br J Anaesth 2000, 84:476-488.
107. Ruan H-Z, Burnstock G. Localisation of P2Y1 and P2Y4 receptors in dorsal root, nodose and trigeminal ganglia of the rat. Histochemistry and Cell Biology 2003, 120:415-426. 10.1007/s00418-003-0579-3, 14564529.
108. Gerevich Z, Borvendeg SJ, Schroder W, Franke H, Wirkner K, Norenberg W, Furst S, Gillen C, Illes P. Inhibition of N-type voltage-activated calcium channels in rat dorsal root ganglion neurons by P2Y receptors is a possible mechanism of ADP-induced analgesia. J Neurosci 2004, 24:797-807. 10.1523/JNEUROSCI.4019-03.2004, 14749424.
109. Tominaga M, Wada M, Masu M. Potentiation of capsaicin receptor activity by metabotropic ATP receptors as a possible mechanism for ATP-evoked pain and hyperalgesia. Proc Natl Acad Sci USA 2001, 98:6951-6956. 10.1073/pnas.111025298, 34459, 11371611.
110. Chizhmakov I, Yudin Y, Mamenko N, Prudnikov I, Tamarova Z, Krishtal O. Opioids inhibit purinergic nociceptors in the sensory neurons and fibres of rat via a G protein-dependent mechanism. Neuropharmacology 2005, 48:639-647. 10.1016/j.neuropharm.2004.12.009, 15814099.
111. Krishtal O, Lozovaya N, Fedorenko A, Savelyev I, Chizhmakov I. The agonists for nociceptors are ubiquitous, but the modulators are specific: P2X receptors in the sensory neurons are modulated by cannabinoids. Pflugers Arch 2006, 453:353-360. 10.1007/s00424-006-0094-1, 16741755.
112. Hausmann R, Rettinger J, Gerevich Z, Meis S, Kassack MU, Illes P, Lambrecht G, Schmalzing G. The suramin analog 4,4',4",4"'-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-benzenesulfonic acid (NF110) potently blocks P2X3 receptors: subtype selectivity is determined by location of sulfonic acid groups. Mol Pharmacol 2006, 69:2058-2067. 10.1124/mol.106.022665, 16551782.
113. Jarvis MF, Burgard EC, McGaraughty S, Honore P, Lynch K, Brennan TJ, Brennan TJ, Subieta A, van Biesen T, Cartmell J, Bianchi B, Niforatos W, Kage K, Yu H, Mikusa J, Wismer CT, Zhu CZ, Chu K, Lee CH, Stewart AO, Polakowski J, Cox BF, Kowaluk E, Williams M, Sullivan J, Faltynek C. A-31 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 7491, 99:17179-17184.
114. Burnstock G. Physiology and pathophysiology of purinergic neurotransmission. Physiol Rev 2007, 87:659-797. 10.1152/physrev.00043.2006, 17429044.
115. Burnstock G. Expanding field of purinergic signaling. Drug Dev Res 2001, 52:1-10.