Mechanisms of visceral sensitization in humans

Chronic Abdominal and Visceral Pain: Theory and Practice

Volumn , Issue , 2006, Pages 141-160

  Sharma, Abhishek ^a   Aziz, Q ^a  

^a UNIVERSITY OF MANCHESTER   (United Kingdom)

Author keywords

[No Author keywords available]

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EID: 79954962862     PISSN: None     EISSN: None     Source Type: Book    
DOI: None     Document Type: Chapter

References (146)

1. Richter JE, Bradley LA, Castell DO. Esophageal chest pain: current controversies in pathogenesis, diagnosis, and therapy. Ann Intern Med 1989; 110(1):66-78.
2. Fullerton S. Functional digestive disorders (FDD) in the year 2000-economic impact. Eur J Surg Suppl 1998; 582:62-64.
3. Ritchie J. Pain from distension of the pelvic colon by inflating a balloon in the irritable colon syndrome. Gut 1973; 14(2):125-132.
4. Richter JE, Barish CF, Castell DO. Abnormal sensory perception in patients with esophageal chest pain. Gastroenterology 1986; 91(4):845-852.
5. Salet GA et al. Responses to gastric distension in functional dyspepsia. Gut 1998; 42(6):823-829.
6. Trimble KC et al. Heightened visceral sensation in functional gastrointestinal disease is not site-specific. Evidence for a generalized disorder of gut sensitivity. Dig Dis Sci 1995; 40(8):1607-1613.
7. Mertz H et al. Altered rectal perception is a biological marker of patients with irritable bowel syndrome. Gastroenterology 1995; 109(1):40-52.
8. Mertz H et al. Symptoms and visceral perception in severe functional and organic dyspepsia. Gut 1998; 42(6):814-822.
9. Treede RD et al. Peripheral and central mechanisms of cutaneous hyperalgesia. Prog Neurobiol 1992; 38(4):397-421.
10. Bueno L et al. Mediators and pharmacology of visceral sensitivity: from basic to clinical investigations. Gastroenterology 1997; 112(5):1714-1743.
11. Gebhart GF. Pathobiology of visceral pain: molecular mechanisms and therapeutic implications: IV. Visceral afferent contributions to the pathobiology of visceral pain. Am J Physiol Gastrointest Liver Physiol 2000; 278(6):834-838.
12. Mendell LM. Modifiability of spinal synapses. Physiol Rev 1984; 64(1):260-324.
13. Geppetti P, Trevisani M. Activation and sensitisation of the vanilloid receptor: role in gastrointestinal inflammation and function. Br J Pharmacol 2004; 141(8):1313-1320.
14. 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(5):787-794.
15. Torebjork HE, Lundberg LE, LaMotte RH. Central changes in processing of mechanoreceptive input in capsaicin-induced secondary hyperalgesia in humans. J Physiol Lond 1992; 448:765-780.
16. Barbara G, Vallance BA, Collins SM. Persistent intestinal neuromuscular dysfunction after acute nematode infection in mice. Gastroenterology 1997; 113(4):1224-1232.
17. Barbara G et al. Role of immunologic factors and cyclooxygenase 2 in persistent postinfective enteric muscle dysfunction in mice. Gastroenterology 2001; 120(7):1729-1736.
18. Su X, Gebhart GF. Mechanosensitive pelvic nerve afferent fibers innervating the colon of the rat are polymodal in character. J Neurophysiol 1998; 80(5):2632-2644.
19. Woolf CJ, Thompson SW. The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states. Pain 1991; 44(3):293-299.
20. Ji RR et al. Central sensitization and LTP: do pain and memory share similar mechanisms? Trends Neurosci 2003; 26(12):696-705.
21. Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science 2000; 288(5472): 1765-1768.
22. Woolf CJ. Somatic pain-pathogenesis and prevention. Br J Anaesth 1995; 75(2):169-176.
23. Jinks SL, Carstens E. Spinal NMDA receptor involvement in expansion of dorsal horn neuronal receptive field area produced by intracutaneous histamine. J Neurophysiol 1998; 79(4):1613-1618.
24. Ren K et al. The effects of a non-competitive NMDA receptor antagonist, MK-801, on behavioral hyperalgesia and dorsal horn neuronal activity in rats with unilateral inflammation. Pain 1992; 50(3):331-344.
25. Chaplan SR, Malmberg AB, Yaksh TL. Efficacy of spinal NMDA receptor antagonism in formalin hyperalgesia and nerve injury evoked allodynia in the rat. J Pharmacol Exp Ther 1997; 280(2):829-838.
26. Willert RP et al. The development and maintenance of human visceral pain hypersensitivity is dependent on the N-methyl-D-aspartate receptor. Gastroenterology 2004; 126(3):683-692.
27. Park KM et al. Effects of intravenous ketamine, alfentanil, or placebo on pain, pinprick hyperalge-sia, and allodynia produced by intradermal capsaicin in human subjects. Pain 1995; 63(2):163-172.
28. Ilkjaer S et al. Effect of systemic N-methyl-D-aspartate receptor antagonist (ketamine) on primary and secondary hyperalgesia in humans. Br J Anaesth 1996; 76(6):829-834.
29. Andersen OK, Felsby S, Nicolaisen L, Bjerring P, Jensen TS, Arendt-Nielsen L. The effect of Keta-mine on stimulation of primary and secondary hyperalgesia areas induced by capsaicin - a double blind placebo controlled, human experimental study. Pain 1996; 66:829-834.
30. Warncke T, Stubhaug A, Jorum E. Ketamine, an NMDA receptor antagonist, suppresses spatial and temporal properties of burn-induced secondary hyperalgesia in man: a double-blind, cross-over comparison with morphine and placebo. Pain 1997; 72:99-106.
31. Reynolds DV. Surgery in the rat during electrical analgesia induced by focal brain stimulation. Science 1969; 164(878):444-445.
32. Willert RP. Receptor mechanisms mediating human oesophageal pain hypersensitivity; PhD report 2005, University of Manchester. Adapted from Rainville P. Brain mechanisms of Pain Affect and Pain Modulation. In Current Opinion in Neurobiology 2002; 12:195-204.
33. Le Bars D, Dickenson AH, Besson JM. Diffuse noxious inhibitory controls (DNIC). I. Effects on dorsal horn convergent neurones in the rat. Pain 1979; 6(3):283-304.
34. Wand-Tetley JI. Historical methods of counter-irritation. Ann Phys Med 1956; 3(3):90-99.
35. Willer JC. Comparative study of perceived pain and nociceptive flexion reflex in man. Pain 1977; 3(1):69-80.
36. Roby-Brami A et al. An electrophysiological investigation into the pain-relieving effects of heterotopic nociceptive stimuli. Probable involvement of a supraspinal loop. Brain 1987; 110(Pt 6): 1497-1508.
37. De Broucker T et al. Diffuse noxious inhibitory controls in man. Involvement of the spinoreticular tract. Brain 1990; 113(Pt 4):1223-1234.
38. Mansour A et al. Anatomy of CNS opioid receptors. Trends Neurosci 1988; 11(7):308-314.
39. Arvidsson U et al. Distribution and targeting of a mu-opioid receptor (MOR1) in brain and spinal cord. J Neurosci 1995; 15(5 Pt 1):3328-3341.
40. Levine JD et al. The narcotic antagonist naloxone enhances clinical pain. Nature 1978; 272(5656):826-827.
41. Pollo A et al. Response expectancies in placebo analgesia and their clinical relevance. Pain 2001; 93(1):77-84.
42. Millan MJ. Descending control of pain. Prog Neurobiol 2002; 66(6):355-474.
43. Suzuki R et al. Superficial NK1-expressing neurons control spinal excitability through activation of descending pathways. Nat Neurosci 2002; 5(12):1319-1326.
44. Oatway MA, Chen Y, Weaver LC. The 5-HT3 receptor facilitates at-level mechanical allodynia following spinal cord injury. Pain 2004; 110(1-2):259-268.
45. Accarino AM, Azpiroz F, Malagelada JR. Attention and distraction: effects on gut perception. Gastroenterology 1997; 113(2):415-422.
46. Ford MJ et al. Psychosensory modulation of colonic sensation in the human transverse and sigmoid colon. Gastroenterology 1995; 109(6):1772-1780.
47. Selye H. Stress and the general adaptation syndrome. Br Med J 1950; 4667:1383-1392.
48. Chrousos GP, Gold PW. The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis. JAMA 1992; 267(9):1244-1252.
49. Mayer EA. The neurobiology of stress and gastrointestinal disease. Gut 2000; 47(6):861-869.
50. Sterling PE, J Fisher S, et al. Handbook of Life Stress, Cognition and Health. New York, 1988: 629-649.
51. Sawchenko PE, Li H-Y, Ericsson A. Circuits and mechanisms governing hypothalamic responses to stress: a tale of two paradigms. In: Mayer EA, Saper CB, eds. The Biological Basis for Mind Body Interactions. Amsterdam: Elsevier Science, 2000:59-75.
52. Bandler R, Price JL, Keay KA. Brain mediation of active and passive emotional coping. In: Mayor EA, Saper CB, eds. The Biological Basis for Mind Body Interactions. Amsterdam: Elsevier Science, 2000:333-349.
53. Vogt BA, Sikes RW, Vogt LJ. Anterior cingulate cortex and the medial pain system. In: Vogt BA, Gabriel M, eds. Neurobiology of Cingulate Cortex and Limbic Thalamus: A Comprehensive Handbook. Boston: Birkhaeuser, 1993:313-344.
54. 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(5): 1276-1285.
55. Meaney MJ et al. Early environmental regulation of forebrain glucocorticoid receptor gene expression: implications for adrenocortical responses to stress. Dev Neurosci 1996; 18(1-2):49-72.
56. Coplan JD et al. Persistent elevations of cerebrospinal fluid concentrations of corticotropin-releasing factor in adult nonhuman primates exposed to early-life stressors: implications for the pathophysiology of mood and anxiety disorders. Proc Natl Acad Sci USA 1996; 93(4):1619-1623.
57. Schott G. Visceral afferents: their contribution to sympathetic dependent' pain. Brain 1994; 117(2):397-413.
58. Green PG et al. Endocrine and vagal controls of sympathetically dependent neurogenic inflammation. Ann NY Acad Sci 1998; 840:282-288.
59. Randich A, Gebhart G. Vagal afferent modulation of nociception. Brain Res Rev 1992; 17:77-99.
60. Diop L et al. Role of vagal afferents in the antinociception produced by morphine and U-50,488H in the colonic pain reflex in rats. Eur J Pharmacol 1994; 257(1-2):181-187.
61. Iovino P et al. The sympathetic nervous system modulates perception and reflex responses to gut distention in humans. Gastroenterology 1995; 108(3):680-686.
62. Cacioppo JTTL, Berntson GG. Handbook of psychophysiology. 2nd ed. 2004.
63. Tougas G et al. Cardiac autonomic function and oesophageal acid sensitivity in patients with non-cardiac chest pain. Gut 2001; 49(5):706-712.
64. Baharav A et al. Fluctuations in autonomic nervous activity during sleep displayed by power spectrum analysis of heart rate variability. Neurology 1995; 45(6):1183-1187.
65. Dixon KE, Thorn BE, Ward LC. An evaluation of sex differences in psychological and physiological responses to experimentally-induced pain: a path analytic description. Pain 2004; 112(1-2):188-196.
66. Dunn AJ, Berridge CW. Physiological and behavioral responses to corticotropin-releasing factor administration: is CRF a mediator of anxiety or stress responses? Brain Res Brain Res Rev 1990; 15(2):71-100.
67. Charney DS, Bremner DJ, Redmond DE. Noradrenergic neural substrates for anxiety and fear: Clinical associations based on preclinical research. In: Kupfer FBD, ed. Psychopharmacology: The Fourth Generation of Progress. New York: Raven Press, 1995:387-395.
68. Chappell PB et al. Alterations in corticotropin-releasing factor-like immunoreactivity in discrete rat brain regions after acute and chronic stress. J Neurosci 1986; 6(10):2908-2914.
69. Korf J, Aghajanian GK, Roth RH. Increased turnover of norepinephrine in the rat cerebral cortex during stress: role of the locus coeruleus. Neuropharmacology 1973; 12(10):933-938.
70. Abercrombie ED, Keller RW Jr., Zigmond MJ. Characterization of hippocampal norepinephrine release as measured by microdialysis perfusion: pharmacological and behavioral studies. Neuroscience 1988; 27(3):897-904.
71. Kawahara H, Kawahara Y, Westerink BH. The role of afferents to the locus coeruleus in the handling stress-induced increase in the release of noradrenaline in the medial prefrontal cortex: a dual-probe microdialysis study in the rat brain. Eur J Pharmacol 2000; 387(3):279-286.
72. Van Bockstaele EJ, Colago EE, Aicher S. Light and electron microscopic evidence for topographic and monosynaptic projections from neurons in the ventral medulla to noradrenergic dendrites in the rat locus coeruleus. Brain Res 1998; 784(1-2):123-138.
73. Van Bockstaele EJ, Colago EE, Valentino RJ. Amygdaloid corticotropin-releasing factor targets locus coeruleus dendrites: substrate for the co-ordination of emotional and cognitive limbs of the stress response. J Neuroendocrinol 1998; 10(10):743-757.
74. Post RM et al. Peptides in the cerebrospinal fluid of neuropsychiatric patients: an approach to central nervous system peptide function. Life Sci 1982; 31(1):1-15.
75. Kling MA et al. Cerebrospinal fluid immunoreactive corticotropin-releasing hormone and adreno-corticotropin secretion in Cushing's disease and major depression: potential clinical implications. J Clin Endocrinol Metab 1991; 72(2):260-271.
76. Brindley DN, Rolland Y. Possible connections between stress, diabetes, obesity, hypertension and altered lipoprotein metabolism that may result in atherosclerosis. Clin Sci (Lond) 1989; 77(5): 453-461.
77. Munck A, Guyre PM, Holbrook NJ. Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocr Rev 1984; 5(1):25-44.
78. Fitch P. Recovering body and soul from PTSD. In American Massage Therapy Association 2000; 1:40-68.
79. Perlstein RS et al. Synergistic roles of interleukin-6, interleukin-1, and tumor necrosis factor in the adrenocorticotropin response to bacterial lipopolysaccharide in vivo. Endocrinology 1993; 132(3):946-952.
80. Sternberg EM et al. The stress response and the regulation of inflammatory disease. Ann Intern Med 1992; 117(10):854-866.
81. Williams CL et al. Corticotropin-releasing factor directly mediates colonic responses to stress. Am J Physiol 1987; 253(4 Pt 1):582-586.
82. Gue M et al. Stress-induced visceral hypersensitivity to rectal distension in rats: role of CRF and mast cells. Neurogastroenterol Motil 1997; 9(4):271-279.
83. Castagliuolo I et al. Acute stress causes mucin release from rat colon: role of corticotropin releasing factor and mast cells. Am J Physiol 1996; 271(5 Pt 1):884-892.
84. Clark JW, Bindra D. Individual differences in pain thresholds. Can J Psychol 1956; 10(2):69-76.
85. Woodrow KM et al. Pain tolerance: differences according to age, sex and race. Psychosom Med 1972; 34(6):548-556.
86. Wolff BB, Jarvik ME. Variations in cutaneous and deep somatic pain sensitivity. Can J Psychol 1963; 17:37-44.
87. Galer BS et al. Individual variability in the response to different opioids: report of five cases. Pain 1992; 49(1):87-91.
88. Portenoy RK, Foley KM, Inturrisi CE. The nature of opioid responsiveness and its implications for neuropathic pain: new hypotheses derived from studies of opioid infusions. Pain 1990; 43(3): 273-286.
89. Mogil JS et al. Heritability of nociception I: responses of 11 inbred mouse strains on 12 measures of nociception. Pain 1999; 80(1-2):67-82.
90. Mogil JS et al. Heritability of nociception II. Types of nociception revealed by genetic correlation analysis. Pain 1999; 80(1-2):83-93.
91. Smeyne RJ et al. Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor gene. Nature 1994; 368(6468):246-249.
92. Indo Y et al. Mutations in the TRKA/NGF receptor gene in patients with congenital insensitivity to pain with anhidrosis. Nat Genet 1996; 13(4):485-488.
93. Sarkar S et al. Contribution of central sensitisation to the development of non-cardiac chest pain. Lancet 2000; 356(9236):1154-1159.
94. Sarkar S et al. The prostaglandin E2 receptor-1 (EP-1) mediates acid-induced visceral pain hyper-sensitivity in humans. Gastroenterology, 2003; 124(1):18-25.
95. Willert R. Receptor mechanisms mediating human oesophageal hypersensitivity. In: Gastrointestinal Sciences. Manchester: University of Manchester, 2005.
96. Worthen SF, Aziz Q, Hobson AR. Effect of anxiety on the sensory and perceptual characteristics of visceral and somatic sensation. Gut 2005; 54(suppl 2):19.
97. McKendrick MW, Read NW. Irritable bowel syndrome-post salmonella infection. J Infect 1994; 29(1):1-3.
98. Spiller RC et al. Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome. Gut 2000; 47(6):804-811.
99. Gwee KA et al. Increased rectal mucosal expression of interleukin 1beta in recently acquired post-infectious irritable bowel syndrome. Gut 2003; 52(4):523-526.
100. Chan JG, W Perry M, et al. IL-10 and TGF-beta genotype in irritable bowel syndrome: evidence to support an inflammatory component? Gastroenterology 2000; 118(suppl 1).
101. Simone DA et al. Neurogenic hyperalgesia: central neural correlates in responses of spinothalamic tract neurons. J Neurophysiol 1991; 66(1):228-246.
102. Dougherty PM, Willis WD. Enhanced responses of spinothalamic tract neurons to excitatory amino acids accompany capsaicin-induced sensitization in the monkey. J Neurosci 1992; 12(3):883-894.
103. Kenshalo DR Jr et al. Facilitation of the response of primate spinothalamic cells to cold and to tactile stimuli by noxious heating of the skin. Pain 1982; 12(2):141-152.
104. Hylden JL et al. Expansion of receptive fields of spinal lamina I projection neurons in rats with unilateral adjuvant-induced inflammation: the contribution of dorsal horn mechanisms. Pain 1989; 37(2):229-243.
105. Verne GN, Robinson ME, Price DD. Hypersensitivity to visceral and cutaneous pain in the irritable bowel syndrome. Pain 2001; 93(1):7-14.
106. Munakata J et al. Repetitive sigmoid stimulation induces rectal hyperalgesia in patients with irritable bowel syndrome. Gastroenterology 1997; 112(1):55-63.
107. Coffin B et al. Alteration of the spinal modulation of nociceptive processing in patients with irritable bowel syndrome. Gut 2004; 53(10):1465-1470.
108. Mayer EA. Spinal and supraspinal modulation of visceral sensation. Gut 2000; 47(suppl 4):iv69-72; discussion iv76.
109. Whitehead WE et al. Effects of stressful life events on bowel symptoms: subjects with irritable bowel syndrome compared with subjects without bowel dysfunction. Gut 1992; 33(6):825-830.
110. Gwee KA et al. The role of psychological and biological factors in postinfective gut dysfunction. Gut 1999; 44(3):400-406.
111. Garrett VD et al. The relation between daily stress and Crohn's disease. J Behav Med 1991; 14(1):87-96.
112. Gwee KA et al. Psychometric scores and persistence of irritable bowel after infectious diarrhoea. Lancet 1996; 347(8995):150-153.
113. Stam R, Akkermans LM, Wiegant VM. Trauma and the gut: interactions between stressful experience and intestinal function. Gut 1997; 40(6):704-709.
114. Drossman DA et al. Sexual and physical abuse and gastrointestinal illness. Review and recommendations. Ann Intern Med 1995; 123(10):782-794.
115. Arntz A, Dreessen L, Merckelbach H. Attention, not anxiety, influences pain. Behav Res Ther 1991; 29(1):41-50.
116. Mertz H et al. Regional cerebral activation in irritable bowel syndrome and control subjects with painful and nonpainful rectal distention. Gastroenterology 2000; 118(5):842-848.
117. Naliboff BD et al. Cerebral activation in patients with irritable bowel syndrome and control subjects during rectosigmoid stimulation. Psychosom Med 2001; 63(3):365-375.
118. Berman S et al. Gender differences in regional brain response to visceral pressure in IBS patients. Eur J Pain 2000; 4(2):157-172.
119. Silverman DH et al. Regional cerebral activity in normal and pathological perception of visceral pain. Gastroenterology 1997; 112(1):64-72.
120. Bonaz B et al. Central processing of rectal pain in patients with irritable bowel syndrome: an fMRI study. Am J Gastroenterol 2002; 97(3):654-661.
121. Chen CL, Orr WC. Autonomic responses to heartburn induced by esophageal acid infusion. J Gas-troenterol Hepatol 2004; 19(8):922-926.
122. Heitkemper M et al. Increased urine catecholamines and cortisol in women with irritable bowel syndrome. Am J Gastroenterol 1996; 91(5):906-913.
123. Heitkemper M et al. Autonomic nervous system function in women with irritable bowel syndrome. Dig Dis Sci 2001; 46(6):1276-1284.
124. Piccirillo G et al. Abnormal passive head-up tilt test in subjects with symptoms of anxiety power spectral analysis study of heart rate and blood pressure. Int J Cardiol 1997; 60(2):121-131.
125. Thayer JF, Friedman BH, Borkovec TD. Autonomic characteristics of generalized anxiety disorder and worry. Biol Psychiatry 1996; 39(4):255-266.
126. Berntson GG et al. Heart rate variability: origins, methods, and interpretive caveats. Psychophysiology 1997; 34(6):623-648.
127. Koizumi K, Kollai M. Multiple modes of operation of cardiac autonomic control: development of the ideas from Cannon and Brooks to the present. J Auton Nerv Syst 1992; 41(1-2):19-29.
128. Fukudo S, Nomura T, Hongo M. Impact of corticotropin-releasing hormone on gastrointestinal motility and adrenocorticotropic hormone in normal controls and patients with irritable bowel syndrome. Gut 1998; 42(6):845-849.
129. Stefanini GF et al. Oral disodium cromoglycate treatment on irritable bowel syndrome: an open study on 101 subjects with diarrheic type. Am J Gastroenterol 1992; 87(1):55-57.
130. Posserud I et al. Altered visceral perceptual and neuroendocrine response in patients with irritable bowel syndrome during mental stress. Gut 2004; 53(8):1102-1108.
131. Patacchioli FR, et al. Actual stress, psychopathology and salivary cortisol levels in the irritable bowel syndrome (IBS). J Endocrinol Invest 2001; 24(3):173-177.
132. Elsenbruch S, Orr WC. Diarrhea- and constipation-predominant IBS patients differ in postprandial autonomic and cortisol responses. Am J Gastroenterol 2001; 96(2):460-466.
133. Morris-Yates A et al. Evidence of a genetic contribution to functional bowel disorder. Am J Gastroenterol 1998; 93(8):1311-1317.
134. Levy RL et al. Irritable bowel syndrome in twins: heredity and social learning both contribute to etiology. Gastroenterology 2001; 121(4):799-804.
135. Kim DY, Camilleri M. Serotonin: a mediator of the brain-gut connection. Am J Gastroenterol 2000; 95(10):2698-2709.
136. Yeo A et al. Association between a functional polymorphism in the serotonin transporter gene and diarrhoea predominant irritable bowel syndrome in women. Gut 2004; 53(10):1452-1458.
137. Lesch KP et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 1996; 274(5292):1527-1531.
138. McCaffery JM et al. Allelic variation in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and cardiovascular reactivity in young adult male and female twins of European-American descent. Psychosom Med 2003; 65(5):721-728.
139. Bharucha AE et al. Adrenergic modulation of human colonic motor and sensory function. Am J Physiol 1997; 273(5 Pt 1):997-1006.
140. Kobilka BK et al. Cloning, sequencing, and expression of the gene coding for the human platelet alpha 2-adrenergic receptor. Science 1987; 238(4827):650-656.
141. Kim HJ et al. Association of distinct alpha(2) adrenoceptor and serotonin transporter polymorphisms with constipation and somatic symptoms in functional gastrointestinal disorders. Gut 2004; 53(6):829-837.
142. Holtmann G et al. G-protein beta 3 subunit 825 CC genotype is associated with unexplained (functional) dyspepsia. Gastroenterology 2004; 126(4):971-979.
143. Kleuss C et al. Different beta-subunits determine G-protein interaction with transmembrane receptors. Nature 1992; 358(6385):424-426.
144. Baumgart D et al. G protein beta3 subunit 825T allele and enhanced coronary vasoconstriction on alpha(2)-adrenoceptor activation. Circ Res 1999; 85(10):965-969.
145. Zill P et al. Evidence for an association between a G-protein beta3-gene variant with depression and response to antidepressant treatment. Neuroreport 2000; 11(9):1893-1897.
146. Lindemann M et al. The G protein beta3 subunit 825T allele is a genetic marker for enhanced T cell response. FEBS Lett 2001; 495(1-2):82-86.