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Neurophysiology of Visceral Pain

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Chronic Pelvic Pain and Pelvic Dysfunctions

Part of the book series: Urodynamics, Neurourology and Pelvic Floor Dysfunctions ((UNPFD))

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Abstract

Visceral pain, particularly chronic pain, is a significant problem for the physical, psychological, social, and economic aspects.

Although it has often been studied by applying the mechanisms of somatic pain, it presents many differences, both in clinical and in physio-pathological aspects.

Despite these differences the current management of visceral pain generally follows the guidelines derived from the somatic pain literature.

However, the knowledge of the key mechanisms underlying chronic visceral plays a fundamental role in the general management of the patient and in the choice of treatment.

In this chapter the anatomical data and the functional aspects that make visceral pain unique will be briefly discussed.

Particularly, clinical presentation, mechanisms of peripheral and central sensitization, and the role of dorsal columns and of descending pathways that modulate spinal nociceptive transmission will be presented.

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References

  1. Norell M, Lythall D, Coghlan G, Cheng A, Kushwaha S, Swan J, Ilsley C, Mitchell A. Limited value of the resting electrocardiogram in assessing patients with recent onset chest pain: lessons from a chest pain clinic. Br Heart J. 1992;67:53–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Klinkman MS, Stevens D, Gorenflo DW. Episodes of care for chest pain: a preliminary report from MIRNET. Michigan Research Network. J Fam Pract. 1994;38:345–52.

    CAS  PubMed  Google Scholar 

  3. Drossman DA, Whitehead WE, Camilleri M. Irritable bowel syndrome: a technical review for practice guideline development. Gastroenterology. 1997;112:2120–37.

    Article  CAS  PubMed  Google Scholar 

  4. Walker EA, Katon WJ, Jemelka RP, Roy-Bryne PP. Comorbidity of gastrointestinal complaints, depression, and anxiety in the Epidemiologic Catchment Area (ECA) study. Am J Med. 1992;92:26S–30S.

    Article  CAS  PubMed  Google Scholar 

  5. Mathias SD, Kuppermann M, Liberman RF, Lipschutz RC, Steege JF. Chronic pelvic pain: prevalence, health-related quality of life, and economic correlates. Obstet Gynecol. 1996;87:321–7.

    Article  CAS  PubMed  Google Scholar 

  6. McLoone M, Lee J. Epidemiology of urogenital pain. In: Baranowski AP, editor. Urogenital pain in practice: Informa Healthcare; 2008. p. 17–21.

    Google Scholar 

  7. Hall SA, Link CL, Pulliam SJ, Hanno PM, Eggers PW, Kusek JW, McKinlay JB. The relationship of common medical conditions and medication use with symptoms of painful bladder syndrome: results from the Boston Area Community Health Survey. J Urol. 2008;180:593–8.

    Article  PubMed  Google Scholar 

  8. Collins MM, Stafford RS, O'Leary MP, Barry MJ. How common is prostatitis? A national survey of physician visits. J Urol. 1998;159:1224–8.

    Article  CAS  PubMed  Google Scholar 

  9. Harlow BL, Stewart EG. A population-based assessment of chronic unexplained vulvar pain: have we underestimated the prevalence of vulvodynia? J Am Med Womens Assoc. 2003;58:82–8.

    Google Scholar 

  10. Kennedy CM, Nygaard IE, Saftlas A, Burns TL, Torner JC, Galask RP. Vulvar disease: a pelvic floor pain disorder? Am J Obstet Gynecol. 2005;192:1829–34.

    Article  PubMed  Google Scholar 

  11. Cervero F. Visceral pain: mechanisms of peripheral and central sensitization. Ann Med. 1995;27:235–9.

    Article  CAS  PubMed  Google Scholar 

  12. Sikandar S, Dickenson AH. Visceral pain: the ins and outs, the ups and downs. Curr Opin Support Palliat Care. 2012;6:17–26.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Cervero F, Laird JM. Visceral pain. Lancet. 1999;353:2145–8.

    Article  CAS  PubMed  Google Scholar 

  14. Giamberardino MA. Visceral pain. IASP Pain Clin Update December 2005; XIII.

    Google Scholar 

  15. Kansal A, Hughes J. Visceral pain. Anaesth Intensive Care Med. 2016;17:543–7.

    Article  Google Scholar 

  16. Arendt-Nielsen L, Svensson P. Referred muscle pain: basic and clinical findings. Clin J Pain. 2001;17(1):11–9.

    Article  CAS  PubMed  Google Scholar 

  17. Vecchiet L, Giamberardino MA, Dragani L, Albe-Fessard D. Pain from renal/ureteral calculosis: evaluation of sensory thresholds in the lumbar area. Pain. 1989;36:289–95.

    Article  CAS  PubMed  Google Scholar 

  18. Cervero F. Somatic and visceral inputs to the thoracic spinal cord of the cat: effects of noxious stimulation of the biliary system. J Physiol. 1983;337:51–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Mertz H, Naliboff B, Munakata J, Niazi N, Mayer EA. Altered rectal perception is a biological marker of patients with irritable bowel syndrome. Gastroenterology. 1995;109:40–52.

    Article  CAS  PubMed  Google Scholar 

  20. Gebhart GF. Visceral pain-peripheral sensitisation. Gut. 2000;47(Suppl 4):iv54-5.

    Google Scholar 

  21. Cervero F. Visceral pain-central sensitization. Gut. 2000;47:56–7.

    Article  Google Scholar 

  22. Gebhart GF, Bielefeldt K. Physiology of visceral pain. Compr Physiol. 2016;6:1609–33.

    Article  CAS  PubMed  Google Scholar 

  23. Olesen AE, Farmer AD, Olesen SS, Aziz Q, Drewes AM. Management of chronic visceral pain. Pain Manag. 2016;6:469–86.

    Article  PubMed  Google Scholar 

  24. Giamberardino MA. In: Devor M, et al., editors. Proceedings of the 9th World Congress on Pain, Progress in Pain Research and Management, vol. 16. Seattle: IASP Press; 2000. p. 523–50.

    Google Scholar 

  25. Giamberardino MA. Recent and forgotten aspects of visceral pain. Eur J Pain. 1999;3(2):77–92.

    Article  CAS  PubMed  Google Scholar 

  26. Giamberardino MA, Costantini R, Affaitati G, Fabrizio A, Lapenna D, Tafuri E, Mezzetti A. Viscero-visceral hyperalgesia: characterization in different clinical models. Pain. 2010;151:307–22.

    Article  PubMed  Google Scholar 

  27. Giamberardino MA, Berkley KJ, Affaitati G, Lerza R, Centurione L, Lapenna D, Vecchiet L. Influence of endometriosis on pain behaviors and muscle hyperalgesia induced by a ureteral calculosis in female rats. Pain. 2002;95(3):247–57.

    Article  PubMed  Google Scholar 

  28. 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:G834–8.

    Article  CAS  PubMed  Google Scholar 

  29. D’Mello R, Dickenson AH. Spinal cord mechanisms of pain. Br J Anaesth. 2008;101:8–16.

    Article  PubMed  Google Scholar 

  30. Julius D, Basbaum AI. Molecular mechanisms of nociception. Nature. 2001;413:203–10.

    Article  CAS  PubMed  Google Scholar 

  31. Gold MS, Gebhart GF. Nociceptor sensitization in pain pathogenesis. Nat Med. 2010;16:1248–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Anand P, Aziz Q, Willert R, van Oudenhove L. Peripheral and central mechanisms of visceral sensitization in man. Neurogastroenterol Motil. 2007;19:29–46.

    Article  CAS  PubMed  Google Scholar 

  33. Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science. 2000;288(5472):1765–9.

    Article  CAS  PubMed  Google Scholar 

  34. Farmer AD, Aziz Q. Mechanisms of visceral pain in health and functional gastrointestinal disorders. Scand J Pain. 2014;5:51–60.

    Article  PubMed  Google Scholar 

  35. Akopian AN, Sivilotti L, Wood JN. A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons. Nature. 1996;379(6562):257–62.

    Article  CAS  PubMed  Google Scholar 

  36. Laird JMA, Fernand C, Parnham MJ, Coward K, Baker MD. Sodium channels, pain, and analgesia. Basel: Birkhäuser Basel; 2005. Voltage-gated sodium channels and visceral pain. p. 63–70.

    Book  Google Scholar 

  37. Gold MS, Zhang L, Wrigley DL, Traub RJ. Prostaglandin E(2) modulates TTX-R I(Na) in rat colonic sensory neurons. J Neurophysiol. 2002;88:1512–22.

    Article  CAS  PubMed  Google Scholar 

  38. Hillsley K, Lin JH, Stanisz A, Grundy D, Aerssens J, Peeters PJ, et al. Dissecting the role of sodium currents in visceral sensory neurons in a model of chronic hyperexcitability using Nav1.8 and Nav1.9 null mice. J Physiol. 2006;576:257–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Laird JM, Souslova V, Wood JN, Cervero F. Deficits in visceral pain and referred hyperalgesia in Nav1.8 (SNS/PN3)-null mice. J Neurosci. 2002;22:8352–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Matthews EA, Wood JN, Dickenson AH. Na(v) 1.8-null mice show stimulus-dependent deficits in spinal neuronal activity. Mol Pain. 2006;2:5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Leo S, D’Hooge R, Meert T. Exploring the role of nociceptor-specific sodium channels in pain transmission using Nav1.8 and Nav1.9 knockout mice. Behav Brain Res. 2010;208:149–57.

    Article  CAS  PubMed  Google Scholar 

  42. 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;389:816–24.

    Article  CAS  PubMed  Google Scholar 

  43. Hwang SW, Oh U. Hot channels in airways: pharmacology of the vanilloid receptor. Curr Opin Pharmacol. 2002;2(3):235–42.

    Article  CAS  PubMed  Google Scholar 

  44. Winston J, Shenoy M, Medley D, Naniwadekar A, Pasricha PJ. The vanilloid receptor initiates and maintains colonic hypersensitivity induced by neonatal colon irritation in rats. Gastroenterology. 2007;132:615–27.

    Article  CAS  PubMed  Google Scholar 

  45. Levine JD, Alessandri-Haber N. TRP channels: targets for the relief of pain. Biochim Biophys Acta. 1772;2007:989–1003.

    Google Scholar 

  46. Hwang SJ, Valtschanoff JG. Vanilloid receptor VR1-positive afferents are distributed differently at different levels of the rat lumbar spinal cord. Neurosci Lett. 2003;349:41–4.

    Article  CAS  PubMed  Google Scholar 

  47. Holzer P. TRPV1 and the gut: from a tasty receptor for a painful vanilloid to a key player in hyperalgesia. Eur J Pharmacol. 2004;500:231–41.

    Article  CAS  PubMed  Google Scholar 

  48. Bortolotti M, Porta S. Effect of red pepper on symptoms of irritable bowel syndrome: preliminary study. Dig Dis Sci. 2011;56:3288–95.

    Article  CAS  PubMed  Google Scholar 

  49. Brock C, Andresen T, Frokjaer JB, Gale J, Olesen AE, Arendt-Nielsen L, et al. Central pain mechanisms following combined acid and capsaicin perfusion of the human oesophagus. Eur J Pain. 2010;14:273–81.

    Article  CAS  PubMed  Google Scholar 

  50. Laird JM, Martinez-Caro L, Garcia-Nicas E, Cervero F. A new model of visceral pain and referred hyperalgesia in the mouse. Pain. 2001;92:335–42.

    Article  CAS  PubMed  Google Scholar 

  51. Sanoja R, Tortorici V, Fernandez C, Price TJ, Cervero F. Role of RVM neurons in capsaicin-evoked visceral nociception and referred hyperalgesia. Eur J Pain (London, England). 2010;14:120.e1-120.

    Article  CAS  Google Scholar 

  52. Gonlachanvit S, Mahayosnond A, Kullavanijaya P. Effects of chili on postprandial gastrointestinal symptoms in diarrhoea predominant irritable bowel syndrome: evidence for capsaicin-sensitive visceral nociception hypersensitivity. Neurogastroenterol Motil. 2009;21:23–32.

    Article  CAS  PubMed  Google Scholar 

  53. Ravnefjord A, Brusberg M, Kang D, Bauer U, Larsson H, Lindstrom E, Martinez V. Involvement of the transient receptor potential vanilloid 1 (TRPV1) in the development of acute visceral hyperalgesia during colorectal distension in rats. Eur J Pharmacol. 2009;611:85–91.

    Article  CAS  PubMed  Google Scholar 

  54. Akbar A, Walters JR, Ghosh S. Review article: visceral hypersensitivity in irritable bowel syndrome: molecular mechanisms and therapeutic agents. Aliment Pharmacol Ther. 2009;30:423–35.

    Article  CAS  PubMed  Google Scholar 

  55. Banerjee B, Medda BK, Lazarova Z, Bansal N, Shaker R, Sengupta JN. Effect of reflux-induced inflammation on transient receptor potential vanilloid one (TRPV1) expression in primary sensory neurons innervating the oesophagus of rats. Neurogastroenterol Motil. 2007;19:681–91.

    Article  CAS  PubMed  Google Scholar 

  56. Akbar A, Yiangou Y, Facer P, Walters JR, Anand P, Ghosh S. Increased capsaicin receptor TRPV1-expressing sensory fibres in irritable bowel syndrome and their correlation with abdominal pain. Gut. 2008;57:923–9.

    Article  CAS  PubMed  Google Scholar 

  57. Gomes RB, Brodskyn C, de Oliveira CI, Costa J, Miranda JC, Caldas A, Valenzuela JG, Barral-Netto M, Barral A. Seroconversion against Lutzomyia longipalpis saliva concurrent with the development of anti-Leishmania chagasi delayed- type hypersensitivity. J Infect Dis. 2002;186:1530–4.

    Article  PubMed  Google Scholar 

  58. Othman AA, Nothaft W, Awni WM, Dutta S. Pharmacokinetics of the TRPV1 antagonist ABT-102 in healthy human volunteers: population analysis of data from 3 phase 1 trials. J Clin Pharmacol. 2012;52:1028–41.

    Article  CAS  PubMed  Google Scholar 

  59. Krarup AL, Ny L, Astrand M, Bajor A, Hvid-Jensen F, Hansen MB, Simren M, Funch-Jensen P, Drewes AM. Randomised clinical trial: the efficacy of a transient receptor potential vanilloid 1 antagonist AZD1386 in human oesophageal pain. Aliment Pharmacol Ther. 2011;33:1113–22.

    Article  CAS  PubMed  Google Scholar 

  60. Quiding H, Jonzon B, Svensson O, Webster L, Reimfelt A, Karin A, Karlsten R, Segerdahl M. TRPV1 antagonistic analgesic effect: a randomized study of AZD1386 in pain after third molar extraction. Pain. 2013;154:808–12.

    Article  CAS  PubMed  Google Scholar 

  61. Al-Chaer ED, Lawand NB, Westlund KN, Willis WD. Visceral nociceptive input into the ventral posterolateral nucleus of the thalamus: a new function for the dorsal column pathway. J Neurophysiol. 1996;76:2661–74.

    Article  CAS  PubMed  Google Scholar 

  62. Palecek J. The role of dorsal columns pathway in visceral pain. Physiol Res. 2004;53(Suppl 1):S125–30.

    PubMed  Google Scholar 

  63. Hirshberg RM, Al-Chaer ED, Lawand NB, Westlund KN, Willis WD. Is there a pathway in the posterior funiculus that signals visceral pain? Pain. 1996;67:291–305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Nauta HJ, Hewitt E, Westlund KN, Willis WD Jr. Surgical interruption of a midline dorsal column visceral pain pathway: case report and review of the literature. J Neurosurg. 1997;86:538–42.

    Article  CAS  PubMed  Google Scholar 

  65. Nauta HJ, Soukup VM, Fabian RH, Lin JT, Grady JJ, Williams CG, Campbell GA, Westlund KN, Willis WD Jr. Punctate mid-line myelotomy for the relief of visceral cancer pain. J Neurosurg. 2000;92(Suppl):125–30.

    CAS  PubMed  Google Scholar 

  66. Becker R, Sure U, Bertalanffy H. Punctate midline myelotomy. A new approach in the management of visceral pain. Acta Neurochir. 1999;141:881–3.

    Article  CAS  PubMed  Google Scholar 

  67. Kim YS, Kwon SJ. High thoracic midline dorsal column myelotomy for severe visceral pain due to advanced stomach cancer. Neurosurgery. 2000;46:85–90.

    Article  CAS  PubMed  Google Scholar 

  68. Al-Chaer ED, Feng Y, Willis WD. A role for the dorsal column in nociceptive visceral input into the thalamus of primates. J Neurophysiol. 1998;79:3143–50.

    Article  CAS  PubMed  Google Scholar 

  69. Houghton AK, Kadura S, Westlund KN. Dorsal column lesions reverse the reduction of homecage activity in rats with pancreatitis. Neuroreport. 1997;8:3795–800.

    Article  CAS  PubMed  Google Scholar 

  70. Feng Y, Cui M, Al-Chaer ED, Willis WD. Epigastric antinociception by cervical dorsal column lesions in rats. Anesthesiology. 1998;89:411–20.

    Article  CAS  PubMed  Google Scholar 

  71. Palecek J, Paleckova V, Willis WD. Fos expression in spinothalamic and postsynaptic dorsal column neurons following noxious visceral and cutaneous stimuli. Pain. 2003;104:249–57.

    Article  CAS  PubMed  Google Scholar 

  72. Lottrup C, Olesen SS, Drewes AM. The pain system in oesophageal disorders: mechanisms, clinical characteristics, and treatment. Gastroenterol Res Pract. 2011:910-420.

    Google Scholar 

  73. Knowles CH, Aziz Q. Basic and clinical aspects of gastrointestinal pain. Pain. 2009;141:191–209.

    Article  PubMed  Google Scholar 

  74. Mayer EA, Aziz Q, Coen S et al. Brain imaging approaches to the study of functional GI disorders: a Rome working team report. Neurogastroenterol Motil 2009; 21: 579–596.

    Google Scholar 

  75. Lelic D, Olesen SS, Valeriani M, Drewes AM. Brain source connectivity reveals the visceral pain network. NeuroImage. 2012;60:37–46.

    Article  PubMed  Google Scholar 

  76. Augustine JR. Circuitry and functional aspects of the insular lobe in primates including humans. Brain Res Rev. 1996;22:229–44.

    Article  CAS  PubMed  Google Scholar 

  77. Bromm B, Scharein E, Vahle-Hinz C. Cortex areas involved in the processing of normal and altered pain. Prog Brain Res. 2000;129:289–302.

    Article  CAS  PubMed  Google Scholar 

  78. Bulmer DC, Roza C. Visceral pain. In: Wood JN, editor. The Oxford handbook of the neurobiology of pain. Subject: Neuroscience, sensory and motor systems, molecular and cellular systems. Online Publication Date: Oct 2018. https://doi.org/10.1093/oxfordhb/9780190860509.013.12.

  79. Garcia-Larrea L. Insights gained into pain processing from patients with focal brain lesions. Neurosci Lett. 2012;520:188–91.

    Article  CAS  PubMed  Google Scholar 

  80. Garcia-Larrea L. The posterior insular-opercular region and the search of a primary cortex for pain. Neurophysiol Clin. 2012;42:299–313.

    Article  CAS  PubMed  Google Scholar 

  81. Garcia-Larrea L, Peyron R. Pain matrices and neuropathic pain matrices: a review. Pain. 2013;154:S29–43.

    Article  PubMed  Google Scholar 

  82. Melzack R. From the gate to the neuromatrix. Pain. 1999;S6:S121–6.

    Article  Google Scholar 

  83. Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. 2009;10:895–926.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Chen X, Tanner K, Levine JD. Mechanical sensitization of cutaneous C-fiber nociceptors by prostaglandin E2 in the rat. Neurosci Lett. 1999;267:105–8.

    Article  CAS  PubMed  Google Scholar 

  85. Guenther S, Reeh PW, Kress M. Rises in [Ca2+]i mediate capsaicin- and proton-induced heat sensitization of rat primary nociceptive neurons. Eur J Neurosci. 1999;11:3143–50.

    Article  CAS  PubMed  Google Scholar 

  86. Hucho T, Levine JD. Signaling pathways in sensitization: toward a nociceptor cell biology. Neuron. 2007;55:365–76.

    Article  CAS  PubMed  Google Scholar 

  87. Petho G, Derow A, Reeh PW. Bradykinin-induced nociceptor sensitization to heat is mediated bycyclooxygenase products in isolated rat skin. Eur J Neurosci. 2001;14:210–8.

    Article  CAS  PubMed  Google Scholar 

  88. Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011;152(3 Suppl):S2–S15.

    Article  PubMed  Google Scholar 

  89. Ness TJ, Metcalf AM, Gebhart GF. A psychophysiological study in humans using phasic colonic distension as a noxious visceral stimulus. Pain. 1990;43:377–86.

    Article  CAS  PubMed  Google Scholar 

  90. Swarbrick ET, Hegarty JE, Bat L, Williams CB, Dawson AM. Site of pain from the irritable bowel. Lancet. 1980;2(8192):443–6.

    Article  CAS  PubMed  Google Scholar 

  91. Sarkar S, Aziz Q, Woolf CJ, Hobson AR, Thompson DG. Contribution of central sensitisation to the development of non-cardiac chest pain. Lancet. 2000;356:1154–9.

    Article  CAS  PubMed  Google Scholar 

  92. Heinricher MM. Pain modulation and the transition from acute to chronic pain. Adv Exp Med Biol. 2016;904:105–15.

    Article  CAS  PubMed  Google Scholar 

  93. Heinricher MM, Tavares I, Leith JL, Lumb BM. Descending control of nociception: specificity, recruitment and plasticity. Brain Res Rev. 2009;60:214–25.

    Article  CAS  PubMed  Google Scholar 

  94. Martins I, Tavares I. Reticular formation and pain: the past and the future. Front Neuroanat. 2017;11:81–4.

    Article  CAS  Google Scholar 

  95. Ness TJ, Gebhart GF. Quantitative comparison of inhibition of visceral and cutaneous spinal nociceptive transmission from the midbrain and medulla in the rat. J Neurophysiol. 1987;58:850–65.

    Article  CAS  PubMed  Google Scholar 

  96. Reynolds DV. Surgery in the rat during electrical analgesia induced by focal brain stimulation. Science (New York, NY). 1969;164:444–5.

    Article  CAS  Google Scholar 

  97. Fields HL, Bry J, Hentall I, Zorman G. The activity of neurons in the rostral medulla of the rat during withdrawal from noxious heat. J Neurosci. 1983;3:2545–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Fields HL, Malick A, Burstein R. Dorsal horn projection targets of ON and OFF cells in the rostral ventromedial medulla. J Neurophysiol. 1995;74:1742–59.

    Article  CAS  PubMed  Google Scholar 

  99. Randich A, Mebane H, DeBerry JJ, Ness TJ. Rostral ventral medulla modulation of the visceromotor reflex evoked by urinary bladder distension in female rats. J Pain. 2008;9:920–6.

    Article  PubMed  PubMed Central  Google Scholar 

  100. Zhuo M, Gebhart GF. Modulation of noxious and non-noxious spinal mechanical transmission from the rostral medial medulla in the rat. J Neurophysiol. 2002;88:2928–41.

    Article  CAS  PubMed  Google Scholar 

  101. Sanoja R, Tortorici V, Fernandez C, Price TJ, Cervero F. Role of RVM neurons in capsaicin- evoked visceral nociception and referred hyperalgesia. Eur J Pain. 2010;14(120):e1–9.

    Google Scholar 

  102. Lloyd-Price J, Abu-Ali G, Huttenhower C. The healthy human microbiome. Genome Med. 2016;8:51.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Pusceddu MM, Gareau MG. Visceral pain: gut microbiota, a new hope? J Biomed Sci. 2018;25:73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Amaral FA, Sachs D, Costa VV, Fagundes CT, Cisalpino D, Cunha TM, Ferreira SH, Cunha FQ, Silva TA, Nicoli JR, Vieira LQ, Souza DG, Teixeira MM. Commensal microbiota is fundamental for the development of inflammatory pain. Proc Natl Acad Sci U S A. 2008;105(6):2193–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. O'Mahony SM, Felice VD, Nally K, Savignac HM, Claesson MJ, et al. Disturbance of the gut microbiota in early-life selectively affects visceral pain in adulthood without impacting cognitive or anxiety-related behaviors in male rats. Neuroscience. 2014;277:885–901.

    Article  CAS  PubMed  Google Scholar 

  106. Gareau MG, Sherman PM, Walker WA. Probiotics and the gut microbiota in intestinal health and disease. Nat Rev Gastroenterol Hepatol. 2010;7(9):503–14.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Rajilic-Stojanovic M, Biagi E, Heilig HG, Kajander K, Kekkonen RA, Tims S, de Vos WM. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology. 2011;141(5):1792–801.

    Article  CAS  PubMed  Google Scholar 

  108. Pusceddu MM, Murray K, Gareau MG. Targeting the microbiota, from irritable bowel syndrome to mood disorders: focus on probiotics and prebiotics. Curr Pathobiol Rep. 2018;6:1–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Camilleri M, Boeckxstaens G. Dietary and pharmacological treatment of abdominal pain in IBS. Gut. 2017;66:966–74.

    Article  CAS  PubMed  Google Scholar 

  110. Enck P, Aziz Q, Barbara G, Farmer AD, Fukudo S, et al. Irritable bowel syndrome. Nat Rev Dis Primers. 2016;2:16014.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Hadizadeh F, Bonfiglio F, Belheouane M, Vallier M, Sauer S, et al. Faecal microbiota composition associates with abdominal pain in the general population. Gut. 2018;67:778–9.

    PubMed  Google Scholar 

  112. Pokusaeva K, Johnson C, Luk B, Uribe G, Fu Y, Oezguen N, et al. GABA-producing Bifidobacterium dentium modulates visceral sensitivity in the intestine. Neurogastroenterol Motil. 2016;29:e12904–14.

    Article  PubMed Central  CAS  Google Scholar 

  113. Guandalini S, Magazzu G, Chiaro A, La Balestra V, Di Nardo G, et al. VSL#3 improves symptoms in children with irritable bowel syndrome: a multicenter, randomized, placebo-controlled, double-blind, crossover study. J Pediatr Gastroenterol Nutr. 2010;51(1):24–30.

    Article  PubMed  Google Scholar 

  114. Kim HJ, Vazquez Roque MI, Camilleri M, Stephens D, Burton DD, Baxter K, Thomforde G, Zinsmeister AR. A randomized controlled trial of a probiotic combination VSL# 3 and placebo in irritable bowel syndrome with bloating. Neurogastroenterol Motil. 2005;17:687–96.

    Article  CAS  PubMed  Google Scholar 

  115. Kim SE, Choi SC, Park KS, Park MI, Shin JE, Lee TH, Jung KW, Koo HS, Myung SJ. Constipation research group of Korean Society of N. and motility. Change of fecal Flora and Effectiveness of the short-term VSL#3 probiotic treatment in patients with functional constipation. J Neurogastroenterol Motil. 2015;21:111–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Michail S, Kenche H. Gut microbiota is not modified by randomized, double-blind, placebo-controlled trial of VSL#3 in diarrhea-predominant irritable bowel syndrome. Probiotics Antimicrob Proteins. 2011;3:1–7.

    Article  PubMed  PubMed Central  Google Scholar 

  117. Harper A, Naghibi M, Garcha D. The role of bacteria, probiotics and diet in irritable bowel syndrome. Foods. 2018;7:13–20.

    Article  PubMed Central  CAS  Google Scholar 

  118. Halkjær SI, Boolsen AW, Günther S, Christensen AH, Petersen AM. Can fecal microbiota transplantation cure irritable bowel syndrome? World J Gastroenterol. 2017;23:4112–20.

    Article  PubMed  PubMed Central  Google Scholar 

  119. Chong PP, Chin VK, Looi CY, Wong WF, Madhavan P, Yong VC. The microbiome and irritable bowel syndrome—a review on the pathophysiology, current research and future therapy. Front Microbiol. 2019;10:1136.

    Article  PubMed  PubMed Central  Google Scholar 

  120. Rossen NG, MacDonald JK, de Vries EM, D'Haens GR, de Vos WM, Zoetendal EG, Ponsioen CY. Fecal microbiota transplantation as novel therapy in gastroenterology: a systematic review. World J Gastroenterol. 2015;21:5359–71.

    Article  PubMed  PubMed Central  Google Scholar 

  121. Rousseaux C, Thuru X, Gelot A, Barnich N, Neut C, et al. Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinoid receptors. Nat Med. 2007;13:35–7.

    Article  CAS  PubMed  Google Scholar 

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Costa, P. (2021). Neurophysiology of Visceral Pain. In: Giammò, A., Biroli, A. (eds) Chronic Pelvic Pain and Pelvic Dysfunctions. Urodynamics, Neurourology and Pelvic Floor Dysfunctions. Springer, Cham. https://doi.org/10.1007/978-3-030-56387-5_2

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