Gastrointestinal pain in functional bowel disordes: Sensory neurons as novel drug targets

Expert Opinion on Therapeutic Targets

Volumn 8, Issue 2, 2004, Pages 107-123

  Holzer, Peter ^a  

^a MEDICAL UNIVERSITY OF GRAZ   (Austria)

Author keywords

5 HT3 and 5 HT4 receptors; Abdominal pain; Acid sensing ion channels; Functional bowel disorders (FBDs); Functional dyspepsia; Gastrointestinal (GI) hyperalgesia; Irritable bowel syndrome (IBS); Purinoceptors; Sensory neurons; Tetrodotoxin resistant; Tetrodotoxin resistant sodium channels; Transient receptor potential channel TRPV1

Indexed keywords

4 (2 PYRIDYL)PIPERAZINE 1 CARBOXAMIDE DERIVATIVE; A 317491; ALOSETRON; AMIDE; CAPSAICIN; CILANSETRON; CISAPRIDE; GABAPENTIN; GLYCINE DERIVATIVE; ION CHANNEL; N (3 ACYLOXY 2 BENZYLPROPYL) N' [4 (METHYLSULFONYLAMINO)BENZYL]THIOUREA VANILLOID DERIVATIVE; OMEGA CONOTOXIN MVIIA; PREGABALIN; PROSTAGLANDIN RECEPTOR BLOCKING AGENT; PURINERGIC RECEPTOR BLOCKING AGENT; RECEPTOR; RECEPTOR BLOCKING AGENT; RESINIFERATOXIN; SB 366791; SC 0030; SODIUM CHANNEL; TEGASEROD; TRANSIENT RECEPTOR POTENTIAL CHANNEL; UNCLASSIFIED DRUG; UREA DERIVATIVE; ZD 6416;

ABDOMINAL DISCOMFORT; DRUG MECHANISM; DRUG TARGETING; DYSPEPSIA; HUMAN; HYPERALGESIA; HYPERSENSITIVITY; INFECTION; INFLAMMATION; INTESTINE FUNCTION DISORDER; IRRITABLE COLON; NERVE CONDUCTION; NERVE ENDING; NERVE EXCITABILITY; NONHUMAN; PREVALENCE; REVIEW; SENSORY NERVE CELL; SPINAL NERVE; VAGUS NERVE; VISCERAL PAIN;

ANALGESICS; COLONIC DISEASES, FUNCTIONAL; DRUG DELIVERY SYSTEMS; HUMANS; NEURONS, AFFERENT; PAIN;

EID: 1842843657     PISSN: 14728222     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728222.8.2.107     Document Type: Review

References (191)

1. DROSSMAN DA, CORAZZLARI E, TALLEY NJ, THOMPSON WG, WHITEHEAD WE (Eds): Rome II. The Functional Gastrointestinal Disorders (2nd edn). Degnon Associates, McLean, USA (2000).
2. MAYER EA, COLLINS SM: Evolving pathophysiologic models of functional gastrointestinal disorders. Gastroenterology (2002) 122:2032-2048.
3. DELVAUX M: Functional bowel disorders and irritable bowel syndrome in Europe. Aliment. Pharmacol. Ther. (2003) 18(Suppl. 3):75-79.
4. TALLEY NJ, DENNIS EH, SCHETTLER-DUNCAN VA, LACY BE, OLDEN KW, CROWELL MD: Overlapping upper and lower gastrointestinal symptoms in irritable bowel syndrome patients with constipation or diarrhea. Am. J. Gastroenterol. (2003) 98:2454-2459.
5. SANDLER RS, EVERHART JE, DONOWITZ M et al.: The burden of selected digestive diseases in the United States. Gastroenterology (2002) 122:1500-1511.
6. INADOMI JM, FENNERTY MB, BJORKMAN D: Systematic review: the economic impact of irritable bowel syndrome. Aliment. Pharmacol. Ther. (2003) 18:671-682.
7. SCHWETZ I, BRADESI S, MAYER EA: Current insights into the pathophysiology of irritable bowel syndrome. Curr. Gastroenterol. Rep. (2003) 5:331-336.
8. MAYER EA, GEBHART GF: Basic and clinical aspects of visceral hyperalgesia. Gastroenterology (1994) 107:271-293.
9. BUENO L, FIORAMONTI J, DELVAUX M, FREXINOS J: Mediators and pharmacology of visceral sensitivity: from basic to clinical investigations. Gastroenterology (1997) 112:1714-1743.
10. AZPIROZ F: Gastrointestinal perception: pathophysiological implications. Neurogastroenterol. Motil. (2002) 14:229-239.
11. BOUIN M, PLOURDE V, BOIVIN M et al.: Rectal distention testing in patients with irritable bowel syndrome: sensitivity, specificity, and predictive values of pain sensory thresholds. Gastroenterology (2002) 122:1771-1777.
12. FURNESS JB, CLERC N: Responses of afferent neurons to the contents of the digestive tract, and their relation to endocrine and immune responses. Prog. Brain Res. (2000) 122:159-172.
13. HOLZER P: Gastrointestinal afferents as targets of novel drugs for the treatment of functional bowel disorders and visceral pain. Eur. J. Pharmacol. (2001) 429:177-193.
14. HOLZER P: Sensory neurone responses to mucosal noxae in the upper gut: relevance to mucosal integrity and gastrointestinal pain. Neurogastroenterol. Motil. (2002) 14:459-475.
15. BERTHOUD HR, NEUHUBER WL: Functional and chemical anatomy of the afferent vagal system. Auton. Neurosci. (2000) 85:1-17.
16. ZAGON A: Does the vagus nerve mediate the sixth sense? Trends Neurosci. (2001) 24:671-673.
17. KERN MK, SHAKER R: Cerebral cortical registration of subliminal visceral stimulation. Gastroenterology (2002) 122:290-298.
18. MALAGELADA JR: The continuing dilemma of dyspepsia. Aliment. Pharmacol. Ther. (2001) 15(Suppl. 1):6-9.
19. KELLOW JE, ECKERSLEY CM, JONES MP: Enhanced perception of physiological intestinal motility in the irritable bowel syndrome. Gastroenterology (1991) 101:1621-1627.
20. SIMREN M, ABRAHAMSSON H, BJÖRNSSON ES: An exaggerated sensory component of the gastrocolonic response in patients with irritable bowel syndrome. Gut (2001) 48:20-27.
21. FASS R, NALIBOFF B, HIGA L et al.: Differential effect of long-term esophageal acid exposure on mechanosensitivity and chemosensitivity in humans. Gastroenterology (1998) 115:1363-1373.
22. TACK J, DEMEDTS I, DEHONDT G et al.: Clinical and pathophysiological characteristics of acute-onset functional dyspepsia. Gastroenterology (2002) 122:1738-1747.
23. SPILLER RC: Postinfectious irritable bowel syndrome. Gastroenterology (2003) 124:1662-1671.
24. CHADWICK VS, CHEN W, SHU D et al.: Activation of the mucosal immune system in irritable bowel syndrome. Gastroenterology (2002) 122:1778-1783.
25. HALL W, BUCKLEY M, CROTTY P, O'MORAIN CA: Gastric mucosal mast cells are increased in Helicobacter pylori-negative functional dyspepsia. Clin. Gastroenterol. Hepatol. (2003) 1:363-369.
26. BARBARA G, STANGHELLINI V, DE GIORGIO R et al.: Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology (2004) 126:693-702.
27. PLOURDE V, ST-PIERRE S, QUIRION R: Calcitonin gene-related peptide in viscerosensitive response to colorectal distension in rats. Am. J. Physiol. (1997) 273(1 Pt 1):G191-G196.
28. 1 receptor gene. Neuroscience (2000) 98:345-352.
29. GSCHOSSMANN JM, COUTINHO SV, MILLER JC et al.: Involvement of spinal calcitonin gene-related peptide in the development of acute visceral hyperalgesia in the rat. Neurogastroenterol. Motil. (2001) 13:229-236.
30. OZAKI N, BIELEFELDT K, SENGUPTA JN, GEBHART GF: Models of gastric hyperalgesia in the rat. Am. J. Physiol. (2002) 283:G666-G676.
31. AL-CHAER ED, KAWASAKI M, PASRICHA PJ: A new model of chronic visceral hypersensitivity in adult rats induced by colon irritation during postnatal development. Gastroenterology (2000) 119:1276-1285.
32. COUTINHO SV, PLOTSKY PM, SABLAD M et al.: Neonatal maternal separation alters stress-induced responses to viscerosomatic nociceptive stimuli in rat. Am. J. Physiol. (2002) 282:G307-G316.
33. LAMB K, KANG YM, GEBHART GF, BIELEFELDT K: Gastric inflammation triggers hypersensitivity to add in awake rats. Gastroenterology (2003) 125:1410-1418.
34. BERCIK P, DE GIORGIO R, BLENNERHASSETT P, VERDU EF, BARBARA G, COLLINS SM: Immune-mediated neural dysfunction in a murine model of chronic Helicobacter pylori infection. Gastroenterology (2002) 123:1205-1215.
35. MOAYYEDI P, DEEKS J, TALLEY NJ, DELANEY B, FORMAN D: An update of the Cochrane systematic review of Helicobacter pylori eradication therapy in nonulcer dyspepsia: resolving the discrepancy between systematic reviews. Am. J. Gastroenterol. (2003) 98:2621-2626.
36. VAIRA D, VAKIL N, RUGGE M et al.: Effect of Helicobacter pylori eradication on development of dyspeptic and reflux disease in healthy asymptomatic subjects. Gut (2003) 52:1543-1547.
37. COUTINHO SV, SU X, SENGUPTA JN, GEBHART GF: Role of sensitized pelvic nerve afferents from the inflamed rat colon in the maintenance of visceral hyperalgesia. Prog. Brain Res. (2000) 129:375-387.
38. 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. (2001) 280:G787-G794.
39. BIELEFELDT K, OZAKI N, GEBHART GF: Experimental ulcers alter voltage-sensitive sodium currents in rat gastric sensory neurons. Gastroenterology (2002) 122:394-405.
40. BIELEFELDT K, OZAKI N, GEBHART GF: Mild gastritis alters voltagr-sensitive sodium currents in gastric sensory neurons in rats. Gastroenterology (2002) 122:752-661.
41. MOORE BA, STEWART TM, HILL C, VANNER SJ: TNBS ileitis evokes hyperexcitability and changes in ionic membrane properties of nociceptive DRG neurons. Am. J. Physiol. (2002) 282:G1045-G1051.
42. DANG K, BIELEFELDT K, GEBHART GF: Gastric ulcers reduce A-Type potassium currents in rat gastric sensory ganglion neurons. Am. J. Physiol. (2004) 286:G573-G579.
43. WOOLF CJ, SALTER MW: Neuronal plasticity: increasing the gain in pain. Science (2000) 288:1765-1768.
44. BIELEFELDT K, OZAKI N, GEBHART GF: Role of nerve growth factor in modulation of gastric afferent neurons in the rat. Am. J. Physiol. (2003) 284:G499-G507.
45. LAMB K, KANG YM, GEBHART GF, BIELEFELDT K: Nerve growth factor and gastric hyperalgesia in the rat. Neurogastroenterol. Motil. (2003) 15:355-361.
46. GONSALKORALE WM, PERREY C, PRAVICA V, WHORWELL PJ, HUTCHINSON IV: Interleukin 10 genotypes in irritable bowel syndrome: evidence for an inflammatory component? Gut (2003) 52:91-93.
47. GWEE KA, COLLINS SM, READ NW et al.: Increased rectal mucosal expression of interleukin 1β in recently acquired post-infectious irritable bowel syndrome. Gut (2003) 52:523-526.
48. WHITEHEAD WE, PAISSON O, JONES KR: Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications? Gastroenterology (2002) 122:1140-1156.
49. HENNINGSEN P, ZIMMERMANN T, SATTEL H: Medically unexplained physical symptoms, anxiety, and depression: a meta-analytic review. Psychosom. Med. (2003) 65:528-533.
50. ANDREWS PL, SANGER GJ: Abdominal vagal afferent neurotics: an important target for the treatment of gastrointestinal dysfunction. Curr. Opin. Pharmacol. (2002) 2:650-656.
51. DONG X, HAN S, ZYLKA MJ, SIMON MI, ANDERSON DJ: A diverse family of GPCRs expressed in specific subsets of nociceptive sensory neurons. Cell (2001) 106:619-632.
52. q/11 pathway. Proc. Natl. Acad. Sci. USA (2002) 99:14740-14745.
53. LEMBO PM, GRAZZINI E, GROBLEWSKI T et al.: Proenkephalin A gene products activate a new family of sensory neuron-specific GPCRs. Nat. Neurosci. (2002) 5:201-209.
54. PERRY MJ, LAWSON SN: Differences in expression of oligosaccharides, neuropeptides, carbonic anhydrase and neurofilament in rat primary afferent neurons retrogradely labelled via skin, muscle or visceral nerves. Neuroscience (1998) 85:293-310.
55. HORNBY PJ: Receptors and transmission in the brain - gut axis. II. Excitatory amino acid receptors in the brain - gut axis. Am. J. Physiol. (2001) 280:G1055-G1060.
56. PARSONS CG: NMDA receptors as targets for drug action in neuropathic pain. Eur. J. Pharmarol. (2001) 429:71-78.
57. LECCI A, VALENTI C, MAGGI CA: Tachykinin receptor antagonists in irritable bowel syndrome. Curr. Opin. Investig. Drugs (2002) 3:589-601.
58. HOLZER P: Role of tachykinins in the gastrointestinal tract. In: Tachykinins. Handbook of Experimental Pharmacology (Vol. 164). Holzer P (Ed.), Springer, Berlin (2004). In Press.
59. DE PONTI F, TONINI M: Irritable bowel syndrome: new agents targeting serotonin receptor subtypes. Drugs (2001) 61:317-332.
60. GERSHON MD: Serotonin and its implication for the management of irritable bowel syndrome. Rev. Gastroenterol. Disord. (2003) 3(Suppl. 2):S25-S34.
61. MIWA J, ECHIZEN H, MATSUEDA K, UMEDA N: Patients with constipation-predominant irritable bowel syndrome (IBS) may have elevated serotonin concentrations in colonic mucosa as compared with diarrhea-predominant patients and subjects with normal bowel habits. Digestion (2001) 63:188-194.
62. CAMILLERI M, ATANASOVA E, CARLSON PJ et al.: Serotonin-transporter polymorphism pharmacogenetics in diarrhea-predominant irritable bowel syndrome. Gastroenterology (2002) 123:425-432.
63. 3 receptor antagonist alosetron inhibits the colorectal distention induced depressor response and spinal c-fos expression in the anaesthetised rat. Gut (2000) 46:474-480.
64. TALLEY NJ: Serotoninergic neuroenteric modulators. Lancet (2001) 358:2061-2068.
65. 4 receptor partial agonist, relieves symptoms in irritable bowel syndrome patients with abdominal pain, bloating and constipation. Aliment. Pharmacol. Ther. (2001) 15:1655-1666.
66. NOVICK J, MINER P, KRAUSE R et al.: A randomized, double-blind, placebo-controlled trial of tegaserod in female patients suffering from irritable bowel syndrome with constipation. Aliment. Pharmacol. Ther. (2002) 16:1877-1888.
67. 4 receptor partial agonist, decreases sensitivity to rectal distension in healthy subjects. Aliment. Pharmacol. Ther. (2003) 17:577-585.
68. 4 receptor partial agonist, tegaserod maleate, inhibits cortical and subcortical c-fos activation following noxious colorectal distension in the mouse. Neurogastroenterol. Motil. (2001) 13:445.
69. SCHIKOWSKI A, THEWISSEN M, MATHIS C, ROSS HG, ENCK P: Serotonin Type-4 receptors modulate the sensitivity of intramural mechanoreceptive afferents of the cat rectum. Neurogastroenterol. Motil. (2002) 14:221-227.
70. BLEY KR, HUNTER JC, EGLEN RM, SMITH JA: The role of IP prostanoid receptors in inflammatory pain. Trends Pharmacol. Sci. (1998) 19:141-147.
71. 2-induced cAMP production and sensitization of sensory neurons. J. Biol. Chem. (2001) 276:16083-16091.
72. HAUPT W, JIANG W, KREIS ME, GRUNDY D: Prostaglandin EP receptor subtypes have distinct effects on jejunal afferent sensitivity in the rat. Gastroenterology (2000) 119:1580-1589.
73. MAUBACH KA, GRUNDY D: The role of Prostaglandins in the bradykinin-induced activation of serosal afferents of the rat jejunum in vitro. J. Physiol. (Lond.) (1999) 515:277-285.
74. 3 in endotoxin-induced enhancement of pain perception. Biochem. Pharmacol. (2001) 62:157-160.
75. 2 receptor-1 (EP-1) mediates acid-induced visceral pain hypersensitivity in humans. Gastroenteroloy (2003) 124:18-25.
76. STEINHOFF M, VERGNOLLE N, YOUNG SH et al.: Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism. Nat. Med. (2000) 6:151-158.
77. HOOGERWERF WA, ZOU L, SHENOY M et al.: The proteinase-activated receptor 2 is involved in nociception. J. Neurosci. (2001) 21:9036-9042.
78. KIRKUP AJ, JIANG W, BUNNETT NW, GRUNDY D: Stimulation of proteinase-activated receptor 2 excites jejunal afferent nerves in anaesthetised rats. J. Physiol. (Lond.) (2003) 552:589-601.
79. COELHO AM, VERGNOLLE N, GUIARD B, FIORAMONTI J, BUENO L: Proteinases and proteinase-activated receptor 2: a possible role to promote visceral hyperalgesia in rats. Gastroenterology (2002) 122:1035-1047.
80. CENAC N, COELHO AM, NGUYEN C et al.: Induction of intestinal inflammation in mouse by activation of proteinase-activated receptor-2. Am. J. Pathol. (2002) 161:1903-1915.
81. NGUYEN C, COELHO AM, GRADY E et al.: Colitis induced by proteinase-activated receptor-2 agonists is mediated by a neurogenic mechanism. Can. J. Physiol. Pharmacol. (2003) 81:920-927.
82. KIM JA, CHOI SC, YUN KJ et al.: Expression of protease-activated receptor 2 in ulcerative colitis. Inflamm. Bowel Dis. (2003) 9:224-229.
83. GAO C, LIU S, HU HZ et al.: Serine proteases excite myenteric neurons through protease-activated receptors in guinea pig small intestine. Gastroenterology (2002) 123:1554-1564.
84. KAWABATA A: Gastrointestinal functions of proteinase-activated receptors. Life Sci. (2003) 74:247-254.
85. DUNN PM, ZHONG Y, BURNSTOCK G: P2X receptors in peripheral neurons. Prog. Neurobiol. (2001) 65:107-134.
86. NORTH RA: Molecular physiology of P2X receptors. Physiol. Rev. (2002) 82:1013-1067.
87. 3-deficient mice. Eur. J. Neurosci. (2001) 14:1784-1792.
88. BURNSTOCK G: Purine-mediated signalling in pain and visceral perception. Trends Pharmacol. Sci. (2001) 22:182-188.
89. 2/3 receptors. Mol. Pharmacol. (1998) 53:969-973.
90. KIRKUP AJ, BOOTH CE, CHESSELL IP, HUMPHREY PP, GRUNDY D: Excitatory effect of P2X receptor activation on mesenteric afferent nerves in the anaesthetised rat. J. Physiol. (Lond.) (1999) 520:551-563.
91. BURGSTAHLER I, GRAFE P: Diadenosine pentaphosphate is more potent than ATP at P2X receptors in isolated rat vagus nerve. Neuroreport (2001) 12:679-682.
92. 3 knock-out mice reveal a major sensory role for urothelially released ATP. J. Neurosci. (2001) 21:5670-5677.
93. WYNN G, RONG W, XIANG Z, BURNSTOCK G: Purinergic mechanisms contribute to mechanosensory transduction in the rat colorectum. Gastroenterology (2003) 125:1398-1409.
94. 3-deficient mice. Nature (2000) 407:1011-1015.
95. PAGE AJ, O'DONNELL TA, BLACKSHAW LA: P2X purinoceptor-induced sensitization of ferret vagal mechanoreceptors in oesophageal inflammation. J. Physiol. (Lond.) (2000) 523:403-411.
96. HOLZER P: Acid-sensitive ion channels in gastrointestinal function. Curr. Opin. Pharmacol. (2003) 3:618-625.
97. XU GY, HUANG LY: Peripheral inflammation sensitizes P2X receptor-mediated responses in rat dorsal root ganglion neurons. J. Neurosci. (2002) 22:93-102.
98. 3 is increased in human inflammatory bowel disease. Neurogastroenterol. Motil. (2001) 13:365-369.
99. GIARONI C, KNIGHT GE, RUAN HZ et al.: P2 receptors in the murine gastrointestinal tract. Neuropharmacology (2002) 43:1313-1323.
100. 2/3 receptors, reduces chronic inflammatory and neuropathic pain in the rat. Proc. Natl. Acad. Sci. USA (2002) 99:17179-17184.
101. 3 receptor antagonist, blocks acetic acid-induced abdominal constriction in mice: comparison with reference analgesics. Pain (2002) 96:99-105.
102. CLAPHAM DE: TRP channels as cellular sensors. Nature (2003) 426:517-524.
103. CLAPHAM DE, MONTELL C, SCHULTZ G, JULIUS D; INTERNATIONAL UNION OF PHARMACOLOGY: International Union of Pharmacology. XLIII. Compendium of voltage-gated ion channels: transient receptor potential channels. Pharmacol. Rev. (2003) 55:591-596.
104. CATERINA MJ, SCHUMACHER MA, TOMINAGA M, ROSEN TA, LEVINE JD, JULIUS D: The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature (1997) 389:816-824.
105. PATAPOUTIAN A, PEIER AM, STORY GM, VISWANATH V: ThermoTRP channels and beyond: mechanisms of temperature sensation: Nat. Rev. Neurosci. (2003) 4:529-539.
106. CATERINA MJ, JULIUS D: The vanilloid receptor: a molecular gateway to the pain pathway. Annu. Rev. Neurosci. (2001) 24:487-517.
107. DI MARZO V, BLUMBERG PM, SZAILASI A: Endovanilloid signaling in pain. Curr. Opin. Neurobiol. (2002) 12:372-379.
108. GUNTHORPE MJ, BENHAM CD, RANDALL A, DAVIS JB: The diversity in the vanilloid (TRPV) receptor family of ion channels. Trends Pharmacol. Sci. (2002) 23:183-191.
109. HWANG SW, OH U: Hot channels in airways: pharmacology of the vanilloid receptor. Curr. Opin. Pharmacol. (2002) 2:235-242.
110. TREVISANI M, SMART D, GUNTHORPE MJ et al.: Ethanol elicits and potentiates nociceptor responses via the vanilloid receptor-1. Nat. Neurosci. (2002) 5:546-551.
111. PREMKUMAR LS, AHERN GP: Induction of vanilloid receptor channel activity by protein kinase C. Nature (2000) 408:985-990.
112. 2 binding site as a determinant of capsaicin receptor sensitivity. Science (2003) 300:1284-1288.
113. REEH PW, PETHÖ G: Nociceptor excitation by thermal sensitization - a hypothesis. Prog. Brain Res. (2000) 129:39-50.
114. CATERINA MJ, LEFFLER A, MALMBERG AB et al.: Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science (2000) 288:306-313.
115. DAVIS JB, GRAY J, GUNTHORPE MJ et al.: Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature (2000) 405:183-187.
116. HOLZER P: Neural emergency system in the stomach. Gastroenterology (1998) 114:823-839.
117. PATTERSON LM, ZHENG H, WARD SM, BERTHOUD HR: Vanilloid receptor (VR1) expression in vagal afferent neurons innervating the gastrointestinal tract. Cell Tissue Res. (2003) 311:277-287.
118. WARD SM, BAYGUINOV J, WON KJ, GRUNDY D, BERTHOUD HR: Distribution of the vanilloid receptor (VR1) in the gastrointestinal tract. J. Comp. Neurol. (2003) 465:121-135.
119. POONYACHOTI S, KULKARNI-NARLA A, BROWN DR: Chemical coding of neurons expressing δ- and κ-opioid receptor and Type I vanilloid receptor immunoreactivities in the porcine ileum. Cell Tissue Res. (2002) 307:23-33.
120. ANAVI-GOFFER S, COUTTS AA: Cellular distribution of vanilloid VR1 receptor immunoreactivity in the guinea-pig myenteric plexus. Eur. J. Pharmacol. (2003) 458:61-71.
121. CHAN CL, FACER P, DAVIS JB et al.: Sensory fibres expressing capsaicin receptor TRPV1 in patients with rectal hypersensitivity and faecal urgency. Lancet (2003) 361:385-391.
122. NOZAWA Y, NISHIHARA K, YAMAMOTO A, NAKANO M, AJIOKA H, MATSUURA N: Distribution and characterization of vanilloid receptors in the rat stomach. Neurosci. Lett. (2001) 309:33-36.
123. SU X, WACHTEL RE, GEBHART GF: Capsaicin sensitivity and voltage-gated sodium currents in colon sensory neurons from rat dorsal root ganglia. Am. J. Physiol. (1999) 277:G1180-G1188.
124. BLACKSHAW LA, PAGE AJ, PARTOSOEDARSO ER: Acute effects of capsaicin on gastrointestinal vagal afferents. Neuroscience (2000) 96:407-416.
125. HAMMER J, HAMMER HF, EHERER AJ, PETRITSCH W, HOLZER P, KREJS GJ: Intraluminal capsaicin does not affect fluid and electrolyte absorption in the human jejunum but does cause pain. Gut (1998) 43:252-255.
126. DREWES AM, SCHIPPER KP, DIMCEVSKI G et al.: Gut pain and hyperalgesia induced by capsaicin: a human experimental model. Pain (2003) 104:333-341.
127. SCHMIDT B, HAMMER J, HOLZER P, HAMMER HF: Chemical nociception in the jejunum induced by capsaicin. Gut (2004). In Press.
128. LAIRD JM, MARTINEZ-CARO L, GARCIA-NICAS E, CERVERO F: A new model of visceral pain and referred hyperalgesia in the mouse. Pain (2001) 92:335-342.
129. HOLZER P: Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory neurons. Pharmacol. Rev. (1991) 43:143-201.
130. SZALLASI A: Vanilloid (capsaicin) receptors in health and disease. Am. J. Clin. Pathol. (2002) 118:110-121.
131. LEMBECK F, SKOFITSCH G: Visceral pain reflex after pretreatment with capsaicin and morphine. Naunyn Schmiedebergs Arch. Pharmacol. (1982) 321:116-122.
132. DELAFOY L, RAYMOND F, DOHERTY AM, ESCHALIER A, DIOP L: Role of nerve growth factor in the trinitrobenzene sulfonic acid-induced colonic hypersensitivity. Pain (2003) 105:489-497.
133. LYSY J, SISTIERY-ITTAH M, ISRAELIT Y et al.: Topical capsaicin - a novel and effective treatment for idiopathic intractable pruritus ani: a randomised, placebo controlled, crossover study. Gut (2003) 52:1323-1326.
134. BORTOLOTTI M, COCCIA G, GROSSI G, MIGLIOLI M: The treatment of functional dyspepsia with red pepper. Aliment. Pharmacol. Ther. (2002) 16:1075-1082.
135. SCHMULSON MJ, VALDOVINOS MA, MILKE P: Chili pepper and rectal hyperalgesia in irritable bowel syndrome. Am. J. Gastroenterol. (2003) 98:1214-1215.
136. YIANGOU Y, FACER P, DYER NH et al.: Vanilloid receptor 1 immunoreactivity in inflamed human bowel. Lancet (2001) 357:1338-1339.
137. JI RR, SAMAD TA, JIN SX, SCHMOLL R, WOOLF CJ: p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron (2002) 36:57-68.
138. MCVEY DC, VIGNA SR: The capsaicin VR1 receptor mediates substance P release in toxin A-induced enteritis in rats. Peptides (2001) 22:1439-1446.
139. KIHARA N, DE LA FUENTE SG, FUJINO K, TAKAHASHI T, PAPPAS TN, MANTYH CR: Vanilloid receptor-1 containing primary sensory neurones mediate dextran sulphate sodium induced colitis in rats. Gut (2003) 52:713-719.
140. +-gated cation channels: neuronal acid sensors in the NaC/DEG family of ion channels. Curr. Opin. Neurobiol. (1998) 8:418-424.
141. KELLENBERGER S, SCHILD L: Epithelial sodium channel/degenerin family of ion channels: a variety of functions for a shared structure. Physiol. Rev. (2002) 82:735-767.
142. KRISHTAL O: The ASICs: signaling molecules? Modulators? Trends Neurosci. (2003) 26:477-483.
143. ALVAREZ DE LA ROSA D, ZHANG P, SHAO D, WHITE F, CANESSA CM: Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system. Proc. Natl. Acad. Sci. USA (2002) 99:2326-2331.
144. +-gated channels in mouse sensory neurons. Proc. Natl. Acad. Sci. USA (2002) 99:2338-2343.
145. ME J, PRICE MP, BERGER AL, WELSH MJ: DRASIC contributes to pH-gated currents in large dorsal root ganglion sensory neurons by forming heteromultimeric channels. J. Neurophysiol. (2002) 87:2835-2843.
146. + channels. J. Biol. Chem. (2002) 277:2369-2372.
147. PRICE MP, LEWIN GR, MCILWRATH SL et al.: The mammalian sodium channel BNC1 is required for normal touch sensation. Nature (2000) 407:1007-1011.
148. PRICE MP, MCILWRATH SL, XIE J et al.: The DRASIC cation channel contributes to the detection of cutaneous touch and acid stimuli in mice. Neuron (2001) 32:1071-1083.
149. CHEN CC, ZIMMER A, SUN WH, HALL J, BROWNSTEIN MJ, ZIMMER A: A role for ASIC3 in the modulation of high-intensity pain stimuli. Proc. Natl. Acad. Sci. USA (2002) 99:8992-8997.
150. YIANGOU Y, FACER P, SMITH JA et al.: Increased acid-sensing ion channel ASIC-3 in inflamed human intestine. Eur. J. Gastroenterol. Hepatol. (2001) 13:891-896.
151. MAMET J, BARON A, LAZDUNSKI M, VOILLEY N: Proinflammatory mediators, stimulators of sensory neuron excitability via the expression of acid-sensing ion channels. J. Neurosci. (2002) 22:10662-10670.
152. OZAKI N, GEBHART GF: Characterization of mechanosensitive splanchnic nerve afferent fibers innervating the rat stomach. Am. J. Physiol. (2001) 281:G1449-G1459.
153. SU X, WACHTEL RE, GEBHART GF: Mechanosensitive potassium channels in rat colon sensory neurons. J. Neurophysiol. (2000) 84:836-843.
154. RAYBOULD HE, GSCHOSSMAN JM, ENNES H, LEMBO T, MAYER EA: Involvement of stretch-sensitive calcium flux in mechanical transduction in visceral afferents. J. Auton. Nerv. Syst. (1999) 75:1-6.
155. SUZUKI M, MIZUNO A, KODAIRA K, IMAI M: Impaired pressure sensation in mice lacking TRPV4. J. Biol. Chem. (2003) 278:22664-22668.
156. + channel family. J. Biol. Chem. (2000) 275:17412-17419.
157. + channels in pain pathways. Trends Pharmacol. Sci. (2001) 22:27-31.
158. v1.9: a sodium channel with unique properties. Trends Neurosci. (2002) 25:253-259.
159. v1.9 (NaN) in nociceptive primary afferent neurons. J. Neurosci. (2002) 22:7425-7433.
160. + channel α subunit protein. J. Physiol. (Lond.) (2003) 546:565-576.
161. v1.8 (SNS/PN3): expression and correlation with membrane properties in rat nociceptive primary afferent neurons. J. Physiol. (Lond.) (2003) 550:739-752.
162. Na in rat colonic sensory neurons. J. Neurophysiol. (2002) 88:1512-1522.
163. STEWART T, BEYAK MJ, VANNER S: Ileitis modulates potassium and sodium currents in guinea pig dorsal root ganglia sensory neurons. J. Physiol. (Lond.) (2003) 552:797-807.
164. v1.8 (PN3/SNS) in a rat model of visceral pain. J. Neurosci. (2001) 21:8690-8696.
165. v1.8 (SNS/PN3 -null mice. J. Neurosci. (2002) 22:8352-8356.
166. NESS TJ: Intravenous lidocaine inhibits visceral nociceptive reflexes and spinal neurons in the rat. Anesthesiology (2000) 92:1685-1691.
167. SU X, JOSHI SK, KARDOS S, GEBHART GF: Sodium channel blocking actions of the κ-opioid receptor agonist U50,488 contribute to its visceral antinociceptive effects. J. Neurophysiol. (2002) 87:1271-1279.
168. BIELEFELDT K, OZAKI N, WHITEIS C, GEBHART GF: Amitriptyline inhibits voltage-sensitive sodium currents in rat gastric sensory neurons. Dig. Dis. Sci. (2002) 47:959-966.
169. CERVERO F, LAIRD JM: Role of ion channels in mechanisms controlling gastrointestinal pain pathways. Curr. Opin. Pharmacol. (2003) 3:608-612.
170. RASBAND MN, PARK EW, VANDERAH TW, LAI J, PORRECA F, TRIMMER JS: Distinct potassium channels on pain-sensing neurons. Proc. Natl. Acad. Sci. USA (2001) 98:13373-13378.
171. 2δ-1 subunit following partial sciatic nerve injury. Mol. Brain Res. (2001) 95:1-8.
172. SUTTON KG, MARTIN DJ, PINNOCK RD, LEE K, SCOTT RH: Gabapentin inhibits high-threshold calcium channel currents in cultured rat dorsal root ganglion neurones. Br. J. Pharmacol. (2002) 135:257-265.
173. EUTAMENE H, COELHO AM, THEODOROU V et al.: Antinociceptive effect of pregabalin in septic shock-induced rectal hypersensitivity in rats. J. Pharmacol. Exp. Ther. (2000) 295:162-167.
174. DIOP L, RAYMOND F, FARGEAU H, PETOUX F, CHOVET M, DOHERTY AM: Pregabalin (CI-1008) inhibits the trinitrobenzene sulfonic acid-induced chronic colonic allodynia in the rat. J. Pharmacol. Exp. Ther. (2002) 302:1013-1022.
175. FENG Y, CUI M, WILLIS WD: Gabapentin markedly reduces acetic acid-induced visceral nociception. Anesthesiology (2003) 98:729-733.
176. JAIN KK: An evaluation of intrathecal ziconotide for the treatment of chronic pain. Expert Opin. Investig. Drugs (2000) 9:2403-2410.
177. HORVATH G, BRODACZ B, HOLZER-PETSCHE U: Role of calcium channels in the spinal transmission of nociceptive information from the mesentery. Pain (2001) 93:35-41.
178. GEBHART GF: Pathobiology of visceral pain: molecular mechanisms and therapeutic implications. IV. Visceral afferent contributions to the pathobiology of visceral pain. Am. J. Physiol. (2000) 278:G834-G838.
179. SANGER GJ, HICKS GA: Drugs targeting functional bowel disorders: insights from animal studies. Curr. Opin. Pharmacol. (2002) 2:678-683.
180. MICHL T, JOCIC M, HEINEMANN A, SCHULIGOI R, HOLZER P: Vagal afferent signaling of a gastric mucosal acid insult to medullary, pontine, thalamic, hypothalamic and limbic, but not cortical, nuclei of the rat brain. Pain (2001) 92:19-27.
181. BLACKSHAW LA, GEBHART GF: The pharmacology of gastrointestinal nociceptive pathways. Curr. Opin. Pharmacol. (2002) 2:642-649.
182. CAMILLERI M: Drugs targeting functional bowel disorders: lessons from drug trials. Curr. Opin. Pharmacol. (2002) 2:684-690.
183. SZALLASI A, BLUMBERG PM: Vanilloid (capsaicin) receptors and mechanisms. Pharmacol. Rev. (1999) 51:159-212.
184. WAHL P, FOGED C, TULLIN S, THOMSEN C: Iodo-resiniferatoxin, a new potent vanilloid receptor antagonist. Mol. Pharmacol. (2001) 59:9-15.
185. GARCIA-MARTINEZ C, HUMET M, PLANELLS-CASES R et al.: Attenuation of thermal nociception and hyperalgesia by VR1 blockers. Proc. Natl. Acad. Sci. USA (2002) 99:2374-2379.
186. WANG Y, SZABO T, WELTER JD et al.: High affinity antagonists of the vanilloid receptor. Mol. Pharmacol. (2002) 62:947-956.
187. LEE J, LEE J, KANG M et al.: N-(3-acyloxy-2-benzylpropyl)-N′-[4-(methylsulfonylamino benzyl]thiourea analogues: novel potent and high affinity antagonists and partial antagonists of the vanilloid receptor. J. Med. Chem. (2003) 46:3116-3126.
188. SUH YG, LEE YS, MIN KH et al.: Novel non-vanilloid VR1 antagonist of high analgesic effects and its structural requirement for VR1 antagonistic effects. Bioorg. Med. Chem. Lett. (2003) 13:4389-4393.
189. SUN Q, TAFESSE L, ISLAM K et al.: 4-(2-Pyridyl)piperazine-1-carboxamides: potent vanilloid receptor 1 antagonists. Bioorg. Med. Chem. Lett. (2003) 13:3611-3616.
190. GUNTHORPE MJ, RAMI HY, JERMAN JC et al.: Identification and characterisation of SB-366791, a potent and selective vanilloid receptor (VR1/TRPV1) antagonist. Neuropharmacology (2004) 46:133-149.
191. MCDONNELL ME, ZHANG SP, NASSER N, DUBIN AE, DAX SL: 7-Hydroxynaphthalen-1-yl-urea and -amide antagonists of human vanilloid receptor 1. Bioorg. Med. Chem. Lett. (2004) 14:531-534.