Advertisement

Visceral Pain: The Neurophysiological Mechanism

  • Jyoti N. Sengupta
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 194)

Abstract

The mechanism of visceral pain is still less understood compared with that of somatic pain. This is primarily due to the diverse nature of visceral pain compounded by multiple factors such as sexual dimorphism, psychological stress, genetic trait, and the nature of predisposed disease. Due to multiple contributing factors there is an enormous challenge to develop animal models that ideally mimic the exact disease condition. In spite of that, it is well recognized that visceral hypersensitivity can occur due to (1) sensitization of primary sensory afferents innervating the viscera, (2) hyperexcitability of spinal ascending neurons (central sensitization) receiving synaptic input from the viscera, and (3) dysregulation of descending pathways that modulate spinal nociceptive transmission. Depending on the type of stimulus condition, different neural pathways are involved in chronic pain. In early-life psychological stress such as maternal separation, chronic pain occurs later in life due to dysregulation of the hypothalamic–pituitary–adrenal axis and significant increase in corticotrophin releasing factor (CRF) secretion. In contrast, in early-life inflammatory conditions such as colitis and cystitis, there is dysregulation of the descending opioidergic system that results excessive pain perception (i.e., visceral hyperalgesia). Functional bowel disorders and chronic pelvic pain represent unexplained pain that is not associated with identifiable organic diseases. Often pain overlaps between two organs and approximately 35% of patients with chronic pelvic pain showed significant improvement when treated for functional bowel disorders. Animal studies have documented that two main components such as (1) dichotomy of primary afferent fibers innervating two pelvic organs and (2) common convergence of two afferent fibers onto a spinal dorsal horn are contributing factors for organ-to-organ pain overlap. With reports emerging about the varieties of peptide molecules involved in the pathological conditions of visceral pain, it is expected that better therapy will be achieved relatively soon to manage chronic visceral pain.

Keywords

Visceral pain Visceral afferents Spinal cord Pelvic nerve Splanchnic nerve Colon Urinary bladder Gender difference Sensitization 

Notes

Acknowledgements

The author acknowledges the support of NIH (RO1 DK062312-A2) to obtain unpublished data reported in this chapter. The author also acknowledges Adrian Miranda and Bidyut K. Medda for their comments and suggestions.

References

  1. Abelli L, Conte B, Somma V, Maggi CA, Giulaini S, Meli A (1989) A method of studying pain arising from the urinary bladder in conscious, freely-moving rats. J Urol 141:148–151PubMedGoogle Scholar
  2. Akbar A, Yiangou Y, Facer P, Walters JR, Anand P, Ghosh S (2008) Increased capsaicin receptor TRPV1 expressing sensory fibres in irritable bowel syndrome and their correlation with abdominal pain. Gut 57(7):923–929PubMedGoogle Scholar
  3. Al-Chaer ED, Kawasaki M, Pasricha PJ (2000) A new model of chronic visceral hypersensitivity in adult rats induced by colon irritation during postnatal development. Gastroenterology 119:1276–1285PubMedGoogle Scholar
  4. Aldskogius H, Elfvin LG, Forsman CA (1986) Primary sensory afferents in the inferior mesenteric ganglion and related nerves of the guinea pig. An experimental study with anterogradely transported wheat germ agglutinin-horseradish peroxidase conjugate. J Auton Nerv Syst 15:179–190PubMedGoogle Scholar
  5. Anand KJ (1998) Clinical importance of pain and stress in preterm neonates. Biol Neonate 73:1–9Google Scholar
  6. Anand KJ, Coskun V, Thirvikraman KV, Nemeroff CB, Plotsky PM (1999) Long-term behavioral effects of repetitive pain in neonatal rat pups. Physiol Behav 66:627–637Google Scholar
  7. Anand KJ, Runeson B, Jacobson B (2004) Gastric suction at birth associated with long-term risk for functional intestinal disorders in later life. J Pedatr 144:449–454Google Scholar
  8. Apostolidis A, Brady CM, Yiangou Y, Davis J, Fowler CJ, Anand P (2005) Capsaicin receptor TRPV1 in urothelium of neurogenic human bladders and effect of intravesical resiniferatoxin. Urology 65:400–405PubMedGoogle Scholar
  9. Applebaum AE, Vance WH, Coggeshall RE (1980) Segmental localization of sensory cell that innervate the bladder. J Comp Neurol 192:203–209PubMedGoogle Scholar
  10. Bahns E, Ernsberger U, Jänig W, Nelke A (1986) Functional characteristics of lumbar visceral afferent from the urinary bladder and urethra in the cat. Pflügers Arch 407:510–518Google Scholar
  11. Bahns E, Halsband U, Jänig W (1987) Responses of visceral afferents from the lower urinary tract, colon and anus to mechanical stimulation. Pflugers Arch 410:296–303PubMedGoogle Scholar
  12. Banerjee B, Medda BK, Lazarova Z, Bansal N, Shaker R, Sengupta JN (2007) Effect of reflux-induced inflammation on transient receptor potential vanilloid one (TRPV1) expression in primary sensory neurons innervating the oesophagus of rats. Neurogastroenterol Motil 19: 681–691PubMedGoogle Scholar
  13. Barber RP, Vaughn JE, Saito K, McLaughlin BJ, Roberts E (1978) GABAergic terminals are presynaptic to primary afferent terminals in the substantia gelatinosa of the rat spinal cord. Brain Res 141:35–55PubMedGoogle Scholar
  14. Baron R, Jänig W, McLachlan EM (1985a) The afferent and sympathetic components of the lumbar spinal outflow to the colon and pelvic organs in the cat. I. The hypogastric nerve. J Comp Neurol 238:135–146PubMedGoogle Scholar
  15. Baron R, Jänig W, McLachlan EM (1985b) The afferent and sympathetic components of the lumbar spinal outflow to the colon and pelvic organs in the cat. II. The lumbar splanchnic nerves. J Comp Neurol 238:147–157PubMedGoogle Scholar
  16. Barreau F, Cartier C, Ferrier L, Fioramonti J, Bueno L (2004a) Nerve growth factor mediates alterations of colonic sensitivity and mucosal barrier induced by neonatal stress in rats. Gastroenterology 127:524–534PubMedGoogle Scholar
  17. Barreau F, Ferrier L, Fioramonti J, Bueno L (2004b) Neonatal maternal deprivation triggers long term alterations in colonic epithelial barrier and mucosal immunity in rats. Gut 53:501–506PubMedGoogle Scholar
  18. Barreau F, Ferrier L, Fioramonti J, Bueno L (2007) New insight in the etiology and pathophysiology of irritable bowel syndrome: contribution of neonatal stress models. Pediatr Res 62:240–245PubMedGoogle Scholar
  19. Berkley KJ, Robbins A, Sato Y (1988) Afferent fibers supplying the uterus in the rat. J Neurophysiol 59:142–163PubMedGoogle Scholar
  20. Berkley KJ, Hotta H, Robbins A, Sato Y (1990) Functional properties of afferent fibers supplying reproductive and other pelvic organs in pelvic nerve of female rat. J Neurophysiol 63(2): 256–272PubMedGoogle Scholar
  21. Berkley KJ, Robbins A, Sato Y (1993) Functional differences between afferent fibers in the hypogastric and pelvic nerves innervating female reproductive organs in the rat. J Neurophysiol 69:533–544PubMedGoogle Scholar
  22. Berkley KJ, Wood E, Scofield SL, Little M (1995) Behavioral responses to uterine or vaginal distension in the rat. Pain 61:121–31PubMedGoogle Scholar
  23. Berthoud HR, Patterson LM, Neumann F, Neuhuber WL (1997) Distribution and structure of vagal afferent intraganglionic laminar endings (IGLEs) in the rat gastrointestinal tract. Anat Embryol 195:183–1891PubMedGoogle Scholar
  24. Berthoud HR, Lynn PA, Blackshaw LA (2001) Vagal and spinal mechanosensors in the rat stomach and colon have multiple receptive fields. Am J Physiol 280:R1371–R1381Google Scholar
  25. Bessou P, Perl ER (1966) A movement receptor of the small intestine. J Physiol Lond 182:404–426PubMedGoogle Scholar
  26. Bielefeldt K, Lamb K, Gebhart GF (2006) Convergence of sensory pathways in the development of somatic and visceral hypersensitivity. Am J Physiol Gastrointest Liver Physiol 291:G658–G665PubMedGoogle Scholar
  27. Birder LA, Kiss S, de Groat WC, Lecci A, Maggi CA (2003) Effect of nepadutant, a neurokinin 2 tachykinin receptor antagonist, on immediate-early gene expression after trinitrobenzene sulfonic acid-induced colitis in the rat. J Pharmacol Exp Ther 304:272–276PubMedGoogle Scholar
  28. Bjorling DE, Elkahwaji JE, Bushman W, Janda LM, Boldon K, Hopkins WJ, Wang ZY (2007) Acute acrolein-induced cystitis in mice. BJU Int 99:1523–1529PubMedGoogle Scholar
  29. Bloomfield AL, Polland WS (1931) Experimental referred pain from the gastrointestinal tract. Part II. Stomach, duodenum and colon. J Clin Invest 10:453–473PubMedGoogle Scholar
  30. Blumberg H, Haupt P, Jänig W, Kohler W (1983) Encoding of visceral noxious stimuli in the discharge patterns of visceral afferent fibers from the colon. Pflugers Arch 398:33–40PubMedGoogle Scholar
  31. Bolser DC, DeGennaro FC, O'Reilly S, Chapman RW, Kreutner W, Egan RW, Hey JA (1994) Peripheral and central site of action of GABA-B agonists to inhibit the cough reflex in the cat and guineapig. Br J Pharmacol 113:1344–1348PubMedGoogle Scholar
  32. Bors EH, Blinn KA (1957) Spinal reflex activity from the vesical mucosa in paraplegic patients. AMA Arch Neurol Psychiatry 78:339–354PubMedGoogle Scholar
  33. Boucher M, Meen M, Codron JP, Coudore F, Kemeny JL, Eschalier A (2000) Cyclophosphamide-induced cystitis in freely-moving conscious rats: behavioral approach to a new model of visceral pain. J Urol 164:203–208PubMedGoogle Scholar
  34. Bradesi S, Eutamene H, Garcia-Villar R, Fioramonti J, Bueno L (2003) Stress-induced visceral hypersensitivity in female rats is estrogen-dependent and involves tachykinin NK1 receptors. Pain 102:227–234PubMedGoogle Scholar
  35. Bradesi S, Lao L, McLean PG, Winchester WJ, Lee K, Hicks GA, Mayer EA (2007) Dual role of 5-HT3 receptors in a rat model of delayed stress-induced visceral hyperalgesia. Pain 130:56–65PubMedGoogle Scholar
  36. Brierley SM, Jones RCW, Gebhart GF, Blackshaw LA (2004) Splanchnic and pelvic mechanosensory afferents signal different qualities of colonic stimuli in mice. Gastroenterology 127:166–178PubMedGoogle Scholar
  37. Brierley SM, Carter R, Jones W 3rd, Xu L, Robinson DR, Hicks GA, Gebhart GF, Blackshaw LA (2005a) Differential chemosensory function and receptor expression of splanchnic and pelvic colonic afferents in mice. J Physiol 567:267–281PubMedGoogle Scholar
  38. Brierley SM, Jones RC 3rd, Xu L, Gebhart GF, Blackshaw LA (2005b) Activation of splanchnic and pelvic colonic afferents by bradykinin in mice. Neurogastroenterol Motil 17:854–862PubMedGoogle Scholar
  39. Burnstock G (2002) Potential therapeutic targets in the rapidly expanding field of purinergic signalling. Clin Med 2:45–53PubMedGoogle Scholar
  40. Burnstock G (2006) Purinergic P2 receptors as targets for novel analgesics. Pharmacol Ther 110:433–454PubMedGoogle Scholar
  41. Caldarella MP, Giamberardino MA, Sacco F, Affaitati G, Milano A, Lerza R, Balatsinou C, Laterza F, Pierdomenico SD, Cuccurullo F, Neri M (2006) Sensitivity disturbances in patients with irritable bowel syndrome and fibromyalgia. Am J Gastroenterol 101:2782–2789PubMedGoogle Scholar
  42. Caldji C, Tannenbaum B, Sharma S, Francis D, Plotsky PM, Meaney MJ (1998) Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat. Proc Natl Acad Sci USA 95:5335–5340PubMedGoogle Scholar
  43. Cameron DM, Brennan TJ, Gebhart GF (2007) Hind paw incision in the rat produces long-lasting colon hypersensitivity. J Pain 9:246–253PubMedGoogle Scholar
  44. Castroman P, Ness TJ (2001) Vigor of visceromotor responses to urinary bladder distension in rats increases with repeated trials and stimulus intensity. Neurosci Lett 306:97–100PubMedGoogle Scholar
  45. Castroman PJ, Ness TJ (2002) Ketamine, an N-methyl-d-aspartate receptor antagonist, inhibits the spinal neuronal responses to distension of the rat urinary bladder. Anesthesiology 96: 1410–1419PubMedGoogle Scholar
  46. Caterina MJ, Julius D (2001) The vanilloid receptor: a molecular gateway to the pain pathway. Ann Rev Neurosci 24:487–517PubMedGoogle Scholar
  47. Caterina MJ, Rosen TA, Tominaga M, Brake AJ, Julius D (1999) A capsaicin-receptor homologue with a high threshold for noxious heat. Nature 398:436–441PubMedGoogle Scholar
  48. Cervero F (1982) Afferent activity evoked by natural stimulation of the biliary system in the ferret. Pain 13:137–151PubMedGoogle Scholar
  49. Cervero F (1983) Somatic and visceral inputs to the thoracic spinal of the cat. J Physiol 337:51–67PubMedGoogle Scholar
  50. Cervero F, Jänig W (1992) Visceral nociceptor: a new world order? Trends Neurosci 15:374–378PubMedGoogle Scholar
  51. Cervero F, Sharkey KA (1988) An electrophysiological and anatomical study of intestinal afferent fibers in the rat. J Physiol Lond 401:381–397PubMedGoogle Scholar
  52. Cervero F, Tattersall JEH (1986) Somatic and visceral sensory integration in the thoracic spinal cord. Prog Brain Res 67:189–205PubMedGoogle Scholar
  53. Chitkara DK, Rawat DJ, Talley NJ (2005) The epidemiology of childhood recurrent abdominal pain in Western countries: a systematic review. Am J Gastrol 100:1868–1875Google Scholar
  54. Chitkara DK, van Tilburg MA, Blois-Martin N, Whitehead WE (2008) Early life risk factors that contribute to irritable bowel syndrome in adults: a systematic review. Am J Gastrol 103:765–774Google Scholar
  55. Christianson JA, Liang R, Ustinova EE, Davis BM, Fraser MO, Pezzone MA (2007) Convergence of bladder and colon sensory innervation occurs at the primary afferent level. Pain 128:235–243PubMedGoogle Scholar
  56. Chuang YC, Fraser MO, Yu Y, Chancellor MB, de Groat WC, Yoshimura N (2001) The role of bladder afferent pathways in bladder hyperactivity induced by the intravesical administration of nerve growth factor. J Urol 165:975–979PubMedGoogle Scholar
  57. Chung EKY, Zhang X, Li Z, Zhang H, Xu HX, Bian ZX (2007a) Neonatal maternal separation enhances central sensitivity to noxious colorectal distension in rat. Brain Res 1153:68–77PubMedGoogle Scholar
  58. Chung EKY, Zhang XJ, Li Z, Xu HX, Sung JJY, Bian ZX (2007b) Visceral hyperalgesia induced by neonatal maternal separation is associated with nerve growth factor-mediated central neural plasticity in rat spinal cord. Neuroscience 149:685–695PubMedGoogle Scholar
  59. Clerc N, Mei N (1983) Thoracic esophageal mechanoreceptor connected with fibers following sympathetic pathways. Brain Res Bull 10:1–7PubMedGoogle Scholar
  60. Clifton GL, Coggeshall RE, Vance WH, Willis WD (1976) Receptive fields of unmyelinated ventral root afferent fibers. J Physiol Lond 256:573–600PubMedGoogle Scholar
  61. Coldwell JR, Phillis BD, Sutherland K, Howarth GS, Blackshaw LA (2007) Increased responsiveness of rat colonic splanchnic afferents to 5-HT after inflammation and recovery. J Physiol 579:203–213PubMedGoogle Scholar
  62. Coutinho SV, Meller ST, Gebhart GF (1996) Intracolonic zymosan produces visceral hyperalgesia in the rat that is mediated by spinal NMDA and non-NMDA receptors. Brain Res 736:7–15PubMedGoogle Scholar
  63. Coutinho SV, Su X, Sengupta JN, Gebhart GF (2000) Role of sensitized pelvic nerve afferents from the inflamed rat colon in the maintenance of visceral hyperalgesia. Prog Brain Res 129:375–387PubMedGoogle Scholar
  64. Coutinho SV, Plotsky PM, Sablad M, Miller JC, Zhou H, Bayati AI, McRoberts JA, Mayer EA (2002) Neonatal maternal separation alters stress-induced responses to viscerosomatic nociceptive stimuli in rat. Am J Physiol 282:G307–G316Google Scholar
  65. Crousillat J, Ranieri F (1980) Mecanorecepteurs splanchniques de la voie biliaire et dedon peritoine. Exp Brain Res 40:146–153PubMedGoogle Scholar
  66. Cruz Y, Downie JW (2006) Abdominal muscle activity during voiding in female rats with normal or irritated bladder. Am J Physiol 290:R1436–R1445Google Scholar
  67. Daly D, Rong W, Chess-Williams R, Chapple C, Grundy D (2007) Bladder afferent sensitivity in wild-type and TRPV1 knockout mice. J Physiol 583:663–674PubMedGoogle Scholar
  68. Dang K, Lamb K, Cohen M, Bielefeldt K, Gebhart GF (2008) Cyclophosphamide-induced bladder inflammation sensitizes and enhances P2X receptor function in rat bladder sensory neurons. J Neurophysiol 99:49–59PubMedGoogle Scholar
  69. Danzebrink RM, Green SA, Gebhart GF (1995) Spinal mu and delta, but not kappa, opioid-receptor agonists attenuate responses to noxious colorectal distension in the rat. Pain 63:39–47PubMedGoogle Scholar
  70. DeBerry J, Ness TJ, Robbins MT, Alan R (2007) Inflammation-induced enhancement of the visceromotor reflex to urinary bladder distension: modulation of endogenous opioids and the effects of early-in-life experience with bladder inflammation. J Pain 8:914–923PubMedGoogle Scholar
  71. Delafoy L, Raymond F, Doherty AM, Eschalier A, Diop L (2003) Role of nerve growth factor in the trinitrobenzene sulfonic acid-induced colonic hypersensitivity. Pain 105:489–497PubMedGoogle Scholar
  72. DinisP, Charrua A, Avelino A, Yaqoob M, Bevan S, Nagy I, Cruz F (2004) Anandamide-evoked activation of vanilloid receptor 1 contributes to the development of bladder hyperreflexia and nociceptive transmission to spinal dorsal horn neurons in cystitis. J Neurosci 24:11253–11263PubMedGoogle Scholar
  73. Diop L, Raymond F, Fargeau H, Petoux F, Chovet M, Doherty AM (2002) Pregabalin (CI-1008) inhibits the trinitrobenzene sulfonic acid-induced chronic colonic allodynia in the rat. J Pharmacol Exp Ther 302:1013–1022PubMedGoogle Scholar
  74. Dmitrieva N, McMahon SB (1996) Sensitisation of visceral afferents by nerve growth factor in the adult rat. Pain 66:87–97PubMedGoogle Scholar
  75. Doran FSA (1967) The site to which pain is referred from the common bile duct in man and implication for the theory of referred pain. Br J Surg 54:599–606PubMedGoogle Scholar
  76. Elson CO, Sartor BR, Tennyson GS, Riddel RH (1995) Experimental models of inflammatory bowel disease. Gastroenterology 109:1344–1367PubMedGoogle Scholar
  77. Evans JP (1936) Observations on the nerves of supply to the bladder and urethra of the cat, with a study of their action potentials. J Physiol 86:396–414PubMedGoogle Scholar
  78. Fall M, Lindström S, Mazières L (1990) A bladder-to-bladder cooling reflex in the cat. J Physiol 427:281–300PubMedGoogle Scholar
  79. Fargeas MJ, Theodorou V, More J, Wal JM, Fioramonti J, Bueno L (1995) Boosted systemic immune and local responsiveness after intestinal inflammation in orally sensitized guinea pigs. Gastroenterology 109:53–62PubMedGoogle Scholar
  80. Fioramonti J, Gaultier E, Toulouse M, Sanger GJ, Bueno L (2003) Intestinal anti-nociceptive behaviour of NK3 receptor antagonism in conscious rats: evidence to support a peripheral mechanism of action. Neurogastroenterol Motil 15:363–369PubMedGoogle Scholar
  81. Fitzerald M (2005) The development of nociceptive circuits. Nat Neurosci 6:507–520Google Scholar
  82. Floyd K, Morrison JFB (1974) Splanchnic mechanoreceptor in the dog. Q J Exp Physiol Cogn Med Sci 59:361–366PubMedGoogle Scholar
  83. Floyd K, Hick EV, Morrison JFB (1976) Mechanosensitive afferent units in the hypogastric nerve of the cat. J Physiol Lond 259:457–471PubMedGoogle Scholar
  84. Floyd K, Hick EV, Koley J, Morrison JFB (1977) The effect of bradykinin on afferent units in intra-abdominal sympathetic nerve trunks. Q J Exp Physiol Cogn Med Sci 62:19–25Google Scholar
  85. Fox EA, Phillips RJ, Martinson FA, Baronowsky EA, Powley TL (2000) Vagal afferent innervation of smooth muscle in the stomach and duodenum of the mouse: morphology and topography. J Comp Neurol 428:558–576PubMedGoogle Scholar
  86. Friedrich AE, Gebhart GF (2000) Effects of spinal cholecystokinin receptor antagonists on morphine antinociception in a model of visceral pain in the rat. J Pharmacol Exp Ther 292:538–544PubMedGoogle Scholar
  87. Friedrich AE, Gebhart GF (2003) Modulation of visceral hyperalgesia by morphine and cholecystokinin from the rat rostroventral medial medulla. Pain 104:93–101PubMedGoogle Scholar
  88. FujinoK, Takami Y, Sebastian G, de la Fuente, Ludwig KA, Christopher R, Mantyh MD (2004) Inhibition of the vanilloid receptor subtype-1 attenuates TNBS-colitis. J Gastrointest Surg 8:842–847PubMedGoogle Scholar
  89. Fujino K, de la Fuente SG, Takami Y, Takahashi T, Mantyh CR (2006) Attenuation of acid-induced oesophagitis in VR-1 deficient mice. Gut 55:34–40PubMedGoogle Scholar
  90. Gammon GD, Bronk DW (1935) The discharges of impulses from pacinian corpuscles in the mesentery and its relation to vascular changes. Am J Physiol 114:77–84Google Scholar
  91. Gareau MG, Jury J, Yang PC, MacQueen G, Perdue MH (2006) Neonatal maternal separation causes colonic dysfunction in rat pups including impaired host resistance. Pediatr Res 59:83–88PubMedGoogle Scholar
  92. Gaudreau GA, Plourde V (2003) Role of tachykinin NK1, NK2 and NK3 receptors in the modulation of visceral hypersensitivity in the rat. Neurosci Lett 351:59–62PubMedGoogle Scholar
  93. Gaudreau GA, Plourde V (2004) Involvement of N-methyl-d-aspartate (NMDA) receptors in a rat model of visceral hypersensitivity. Behav Brain Res 150:185–189PubMedGoogle Scholar
  94. Geirsson G, Lindström S, Fall M (1993) The bladder cooling reflex in man – characteristics and sensitivity to temperature. Br J Urol 71:675–680PubMedGoogle Scholar
  95. Geirsson G, Lindström S, Fall M (1999) The bladder cooling reflex and the use of cooling as stimulus to the lower urinary tract. J Urol 162:1890–1896PubMedGoogle Scholar
  96. Gershon MD, Liu MT (2007) Serotonin and neuroprotection in functional bowel disorders. Neurogastroenterol Motil 19(Suppl 2):19–24PubMedGoogle Scholar
  97. Giamberardino MA, Valente R, de Bigontina P, Vecchiet L (1995) Artificial ureteral calculosis in rats: behavioural characterization of visceral pain episodes and their relationship with referred lumbar muscle hyperalgesia. Pain 61:459–469PubMedGoogle Scholar
  98. Greenwood-Van Meerveld B (2007) Importance of 5-hydroxytryptamine receptors on intestinal afferents in the regulation of visceral sensitivity. Neurogastroenterol Motil 19(Suppl 2):13–18PubMedGoogle Scholar
  99. Greenwood-Van Meerveld B, Gibson MS, Johnson AC, Venkova K, Sutkowski-Markmann D (2003) NK1 receptor-mediated mechanisms regulate colonic hypersensitivity in the guinea pig. Pharmacol Biochem Behav 74:1005–1013PubMedGoogle Scholar
  100. Greenwood-Van Meerveld B, Venkova K, Hicks G, Dennis E, Crowell MD (2006) Activation of peripheral 5-HT receptors attenuates colonic sensitivity to intraluminal distension. Neurogastroenterol Motil 18(1):76–86PubMedGoogle Scholar
  101. Grundy D, Scratcherd T (1989) Sensory afferents from the gastrointestinal tract. In: Handbook of physiology; gastrointestinal system, vol 1. American Physiological Society, Bethesda, pp 593–620Google Scholar
  102. Häbler J, Jänig W, Koltzenburg M (1988a) A novel type of unmyelinated chemosensitive nociceptor in the acutely inflamed urinary bladder. Agent Act 25:219–212Google Scholar
  103. Häbler HJ, Jänig W, Koltzenburg M (1988b) Dichotomizing unmyelinated afferents supplying pelvic viscera and perineum are rare in the sacral segments of the cat. Neurosci Lett 94:119–124PubMedGoogle Scholar
  104. Häbler J, Jänig W, Koltzenburg M (1990) Activation of unmyelinated afferent fibers by mechanical stimuli and inflammation of the urinary bladder of the cat. J Physiol Lond 425:545–562PubMedGoogle Scholar
  105. Häbler J, Jänig W, Koltzenburg M (1991) Spinal cord integration of colon function: Afferent and efferent pathways. In: Y Tache, D Wingate (eds) Brain–gut interactions. CRC, Boca Raton, pp 147–160Google Scholar
  106. Häbler HJ, Jänig W, Koltzenburg M (1993) Myelinated primary afferents of the sacral spinal cord responding to slow filling and distension of the cat urinary bladder. J Physiol 463:449–460PubMedGoogle Scholar
  107. Hammer K, Sann H, Pierau FK (1993) Functional properties of mechanosensitive units from the chicken ureter in vitro. Pflugers Arch 425:353–361PubMedGoogle Scholar
  108. Hara K, Saito Y, Kirihara Y, Yamada Y, Sakura S, Kosaka Y (1999) The interaction of antinociceptive effects of morphine and GABA receptor agonists within the rat spinal cord. Anesth Analg 89:422–427PubMedGoogle Scholar
  109. Haupt P, Jänig W, Kohler W (1983) Response patterns of visceral afferent fibers, supplying the colon, upon chemical and mechanical stimuli. Pflugers Arch 398:41–47PubMedGoogle Scholar
  110. Hicks GA, Coldwell JR, Schindler M, Ward PA, Jenkins D, Lynn PA, Humphrey PP, Blackshaw LA (2002) Excitation of rat colonic afferent fibres by 5-HT(3) receptors. J Physiol 544:861–869PubMedGoogle Scholar
  111. Hong SK, Han HC, Yoon YW, Chung JM (1993) Response properties of hypogastric afferent fibers supplying the uterus in the cat. Brain Res 622(1–2):215–225PubMedGoogle Scholar
  112. Hulsebosch CE, Coggeshall RE (1982) An analysis of the axon populations in the nerve to the pelvic viscera in the rat. J Comp Neurol 211:1–10PubMedGoogle Scholar
  113. Iggo A (1955) Tension receptors in the stomach and urinary bladder. J Physiol Lond 128:593–607PubMedGoogle Scholar
  114. Isomoto S, Kaibara M, Sakurai-Yamashita Y, Nagayama Y, Uenzo Y, Yano K, Taniyama K (1998) Cloning and tissue distribution of novel splice variants of the rat GABAB receptor. Biochem Biophys Res Comm 253:10–15PubMedGoogle Scholar
  115. Jänig W, Koltzenburg M (1990) On the function of spinal primary afferent fibers supplying colon and urinary bladder. J Auton Nerv Syst 30:S89–S96PubMedGoogle Scholar
  116. Jänig W, Koltzenburg M (1991) Receptive properties of sacral primary afferent neurons supplying the colon. J Neurophysiol 65:1067–1077PubMedGoogle Scholar
  117. Jänig W, McLachlan EM (1987) Organization of lumbar spinal outflow to distal colon and pelvic organs. Physiol Rev 67:1332–1404PubMedGoogle Scholar
  118. Jänig W, Morrison JFB (1986) Functional properties of spinal visceral afferents supplying abdominal and pelvic organs, with special emphasis on visceral nociception. In: Visceral sensation. Progress in brain research, vol 67. Elsevier, Amsterdam, pp 87–114Google Scholar
  119. Jänig W, Khasar SG, Levine JD, Miao FJ (2000) The role of vagal visceral afferents in the control of nociception. Prog Brain Res 122:273–287PubMedGoogle Scholar
  120. Ji Y, Traub RJ (2001) Spinal NMDA receptors contribute to neuronal processing of acute noxious and nonnoxious colorectal stimulation in the rat. J Neurophysiol 86:1783–1791PubMedGoogle Scholar
  121. Jiang CH, Mazieres L, Lindstr­m S (2002) Cold- and menthol-sensitive C afferents of cat urinary bladder. J Physiol 543:211–220Google Scholar
  122. Jones RC III, Xu L, Gebhart GF (2005) The mechanosensitivity of mouse colon afferent fibers and their sensitization by inflammatory mediators require transient receptor potential vanilloid 1 and acid-sensing ion channel 3. J Neurosci 25:10981–10989Google Scholar
  123. Jones RCIII, Otsuka E, Wagstrom E, Jensen CS, Price MP, Gebhart GF (2007) Short-term sensitization of colon mechanoreceptors is associated with long-term hypersensitivity to colon distention in the mouse. Gastroenterology 133:184–194PubMedGoogle Scholar
  124. Joshi SK, Su X, Porreca F, Gebhart GF (2000) Kappa-opioid receptor agonists modulate visceral nociception at a novel, peripheral site of action. J Neurosci 20:5874–5879PubMedGoogle Scholar
  125. Joshi SK, Lamb K, Bielefeldt K, Gebhart GF (2003) Arylacetamide kappa-opioid receptor agonists produce a tonic- and use-dependent block of tetrodotoxin-sensitive and -resistant sodium currents in colon sensory neurons. J Pharmacol Exp Ther 307:367–372PubMedGoogle Scholar
  126. Julia V, Morteau O, Buéno L (1994) Involvement of neurokinin 1 and 2 receptors in viscerosensitive response to rectal distension in rats. Gastroenterology 107:94–102PubMedGoogle Scholar
  127. Julia V, Su X, Buéno L, Gebhart GF (1999) Role of neurokinin 3 receptors on responses to colorectal distention in the rat: electrophysiological and behavioral studies. Gastroenterology 116:1124–1131PubMedGoogle Scholar
  128. Kakol-Palm D, Brusberg M, Sand E, Larsson H, Martinez V, Johansson A, von Mentzer B, Påhlman I, Lindström E (2008) Role of tachykinin NK(1) and NK(2) receptors in colonic sensitivity and stress-induced defecation in gerbils. Eur J Pharmacol 582:123–131PubMedGoogle Scholar
  129. Kamp EH, Beck DR, Gebhart GF (2001) Combinations of neurokinin receptor antagonists reduce visceral hyperalgesia. J Pharmacol Exp Ther 299:105–113PubMedGoogle Scholar
  130. Kirchner A, Birklein F, Stefan H, Handwerker HO (2000) Left vagus nerve stimulation suppresses experimentally induced pain. Neurology 55(8):1167–1171PubMedGoogle Scholar
  131. Kolhekar R, Gebhart GF (1994) NMDA and quisqualate modulation of visceral nociception in the rat. Brain Res 651:215–226PubMedGoogle Scholar
  132. Kolhekar R, Gebhart GF (1996) Modulation of spinal visceral nociceptive transmission by NMDA receptor activation in the rat. J Neurophysiol 75:2344–2353PubMedGoogle Scholar
  133. Kozlowski CM, Green A, Grundy D, Boissonade FM, Bountra C (2000) The 5-HT(3) receptor antagonist alosetron inhibits the colorectal distention induced depressor response and spinal c-fos expression in the anaesthetized rat. Gut 46:474–480PubMedGoogle Scholar
  134. Laird JM, Roza C, Cervero F (1996) Spinal dorsal horn neurons responding to noxious distension of the ureter in anesthetized rats. J Neurophysiol 5:3239–3248Google Scholar
  135. Laird JM, Olivar T, Roza C, De Felipe C, Hunt SP, Cervero F (2000) Deficits in visceral pain and hyperalgesia of mice with a disruption of the tachykinin NK1 receptor gene. Neuroscience 98:345–352PubMedGoogle Scholar
  136. Laird JM, Roza C, De Felipe C, Hunt SP, Cervero F (2001a) Role of central and peripheral tachykinin NK1 receptors in capsaicin-induced pain and hyperalgesia in mice. Pain 90:97–103PubMedGoogle Scholar
  137. Laird JM, Olivar T, Lopez-Garcia JA, Maggi CA, Cervero F (2001b) Responses of rat spinal neurons to distension of inflamed colon: role of tachykinin NK2 receptors. Neuropharmacology 40:696–701PubMedGoogle Scholar
  138. Lamb K, Zhong F, Gebhart GF, Bielefeldt K (2006) Experimental colitis in mice and sensitization of converging visceral and somatic afferent pathways. Am J Physiol 290:G451–G457Google Scholar
  139. Lennander KB (1901) Ueber die sensibilität der bauchhohle und ueber lokale und allgemeine anasthesie bei bruch und bauchoperationen. Zentralbl Chir 28:200–223Google Scholar
  140. Lew WYW, Longhurst JC (1986) Substance-P, 5-hydroxytryptamine, and bradykinin stimulate abdominal visceral afferent fiber endings in cats. Am J Physiol 250:R465–R473PubMedGoogle Scholar
  141. Lewis T, Kellgren JH (1939) Observation related to referred pain, viscerosomatic reflexes and other associated phenomena. Clin Sci 4:47–71Google Scholar
  142. Li J, McRoberts JA, Ennes HS, Trevisani M, Nicoletti P, Mittal Y, Mayer EA (2006) Experimental colitis modulates the functional properties of NMDA receptors in dorsal root ganglia neurons. Am J Physiol 291:G219–G228Google Scholar
  143. Liang R, Ustinova EE, Patnam R, Fraser MO, Gutkin DW, Pezzone MA (2007) Enhanced expression of mast cell growth factor and mast cell activation in the bladder following the resolution of trinitrobenzene sulfonic acid (TNBS) colitis in female rats. Neurourol Urodyn 226:887–893Google Scholar
  144. Lidow MS, Song ZM, Ren K (2001) Long-term effects of short-lasting early local inflammatory insult. Neuroreport 12:399–403PubMedGoogle Scholar
  145. Lin C, Al-Chaer ED (2003) Long-term sensitization of primary afferents in adult rats exposed to neonatal colon pain. Brain Res 971:73–82PubMedGoogle Scholar
  146. Lindström S, Mazières L (1991) Effect of menthol on the bladder cooling reflex in the cat. Acta Physiol Scand 141:1–10PubMedGoogle Scholar
  147. Liu D, Diorio J, Tannenbaum B, Caldji C, Francis D, Freedman A, Sharma S, Pearson D, Plotsky PM, Meaney MJ (1997) Maternal care, hippocampal glucocorticoid receptors, and hypothalamic–pituitary–adrenal responses to stress. Science 277:1659–1662PubMedGoogle Scholar
  148. Longhurst JC, Dittman LE (1987) Hypoxia, bradykinin and prostaglandins stimulate ischemically sensitive visceral afferents. Am J Physiol 253:H556–H567PubMedGoogle Scholar
  149. Longhurst JC, Kaufman MP, Ordway GA, Musch TI (1984) Effects of bradykinin and capsaicin on endings of afferent fibers from abdominal visceral organs. Am J Physiol 247:R552–R559PubMedGoogle Scholar
  150. Longhurst JC, Rotto DM, Kaufman MP, Stahl GL (1991) Ischemically sensitive abdominal visceral afferents: response to cyclooxygenase blockade. Am J Physiol 261:H2075–H2081PubMedGoogle Scholar
  151. Longstreth GF (1994) Irritable bowel syndrome and chronic pelvic pain. Obstet Gynecol Surv 49:505–507PubMedGoogle Scholar
  152. Longstreth GF, Drossman DA (2002) New developments in the diagnosis and treatment of irritable bowel syndrome. Curr Gastroenterol Rep 4:427–434PubMedGoogle Scholar
  153. Lu Y, Westlund KN (2001) Effects of baclofen on colon inflammation-induced Fos, CGRP and SP expression in spinal cord and brainstem. Brain Res 889:118–130PubMedGoogle Scholar
  154. Lynn PA, Blackshaw LA (1999) In vitro recordings of afferent fibres with receptive fields in the serosa, muscle and mucosa of rat colon. J Physiol 518:271–282PubMedGoogle Scholar
  155. Lynn PA, Olsson C, Zagorodnyuk V, Costa M, Brookes SJ (2003) Rectal intraganglionic laminar endings are transduction sites of extrinsic mechanoreceptors in the guinea pig rectum. Gastroenterology 125:786–794PubMedGoogle Scholar
  156. Lynn P, Zagorodnyuk V, Hennig G, Costa M, Brookes S (2005) Mechanical activation of rectal intraganglionic laminar endings in the guinea pig distal gut. J Physiol 564:589–601PubMedGoogle Scholar
  157. Mackenzie, J (1893) Some points bearing on the association of sensory disorders and visceral disease. Brain 16:321–353Google Scholar
  158. Malcangio M, Bowery NG (1996) GABA and its receptors in the spinal cord. Trends Pharmacol Sci 17:457–462PubMedGoogle Scholar
  159. Malykhina AP (2007) Neural mechanisms of pelvic organ cross-sensitization. Neuroscience 149:660–672PubMedGoogle Scholar
  160. Malykhina AP, Qin C, Greenwood-van Meerveld B, Foreman RD, Lupu F, Akbarali HI (2006) Hyperexcitability of convergent colon and bladder dorsal root ganglion neurons after colonic inflammation: mechanism for pelvic organ cross-talk. Neurogastroenterol Motil 18:936–948PubMedGoogle Scholar
  161. Marvizón JC, Martínez V, Grady EF, Bunnett NW, Mayer EA (1997) Neurokinin 1 receptor internalization in spinal cord slices induced by dorsal root stimulation is mediated by NMDA receptors. J Neuroscience 17:8129–8136Google Scholar
  162. Marvizon JC, Grady EF, Stefani E, Bunnett NW, Mayer EA (1999) Substance P release in the dorsal horn assessed by receptor internalization: NMDA receptors counteract a tonic inhibition by GABAB receptors. Eur J Neurosci 11:417–426PubMedGoogle Scholar
  163. Marvizón JC, McRoberts JA, Ennes HS, Song B, Wang X, Jinton L, Corneliussen B, Mayer EA (2002) Two N-methyl-d-aspartate receptors in rat dorsal root ganglia with different subunit composition and localization. J Comp Neurol 446:325–341PubMedGoogle Scholar
  164. Matthews MR, Connaughton M, Cuello AC (1987) Ultrastructure and distribution of substance P-immunoreactive sensory collaterals in the guinea pig prevertebral sympathetic ganglia. J Comp Neurol 258:28–51PubMedGoogle Scholar
  165. Matthews PJ, Aziz Q, Facer P, Davis JB, Thompson DG, Anand P (2004) Increase Capsaicin Receptor TRPV1 nerve fibers in the inflamed human oesophagus. Eur J Gastroenterol Hepatol 16:897–902PubMedGoogle Scholar
  166. Mayer EA, Gebhart GF (1994) Basic and clinical aspects of visceral hyperalgesia. Gastroenterology 107:271–293PubMedGoogle Scholar
  167. McMahon SB, Morrison JF (1982) Two group of spinal interneurones that respond to stimulation of the abdominal viscera of the cat. J Physiol 322:21–34PubMedGoogle Scholar
  168. McRoberts JA, Coutinho SV, Marvizón JC, Grady EF, Tognetto M, Sengupta JN, Ennes HS, Chaban VV, Amadesi S, Creminon C, Lanthorn T, Geppetti P, Bunnett NW, Mayer EA (2001) Role of peripheral N-methyl-d-aspartate (NMDA) receptors in visceral nociception in rats. Gastroenterology 120:1737–1748PubMedGoogle Scholar
  169. McRoberts JA, Li J, Ennes HS, Mayer EA (2007) Sex-dependent differences in the activity and modulation of N-methyl-d-aspartic acid receptors in rat dorsal root ganglia neurons. Neuroscience 148(4):1015–20PubMedGoogle Scholar
  170. Mei N (1985) Intestinal chemosensitivity. Physiol Rev 65:211–237PubMedGoogle Scholar
  171. Miampamba M, Sharkey K (1998) Distribution of calcitonin gene-related peptide, somatostatin, substance P and vasoactive intestinal polypeptide in experimental colitis in rats. Neurogastroenterol Motil 10:315–329PubMedGoogle Scholar
  172. Miranda A, Peles S, Rudolph C, Shaker R, Sengupta JN (2004) Altered visceral sensation in response to somatic pain in the rat. Gastroenterology 126:1082–1089PubMedGoogle Scholar
  173. Miranda A, Peles S, Shaker R, Rudolph C, Sengupta JN (2006) Neonatal nociceptive somatic stimulation differentially modifies the activity of spinal neurons in rats and results in altered somatic and visceral sensation. J Physiol 572:775–785PubMedGoogle Scholar
  174. Miranda A, Nordstrom E, Smith C, Sengupta JN (2007) The Role of TRPV1 in Mechanical and Chemical Visceral Hyperalgesia Following Experimental Colitis. Neuroscience 148: 1021–1032PubMedGoogle Scholar
  175. Mitsui T, Kakizaki H, Matsuura S, Ameda K, Yoshioka M, Koyanagi T (2001) Afferent fibers of the hypogastric nerves are involved in the facilitating effects of chemical bladder irritation in rats. J Neurophysiol 86:2276–2284PubMedGoogle Scholar
  176. Mori T, Kawano K, Shishikura T (2004) 5-HT3-receptor antagonist inhibits visceral pain differently in chemical and mechanical stimuli in rats. J Pharmacol Sci 94:73–76PubMedGoogle Scholar
  177. Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL (1989) Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 96:795–803PubMedGoogle Scholar
  178. Morrison JFB (1973) Splanchnic slowly adapting mechanoreceptor with punctate receptive fields in the mesentery and gastrointestinal tract of the cat. J Physiol Lond 233:340–361Google Scholar
  179. Morrison JFB (1987) Sensation arising from the lower urinary tract. In: Torrens M, Morrison JFB (eds) Physiology of the lower urinary tract. Springer, New York, pp 89–131Google Scholar
  180. Morteau O, Hachet T, Caussette M, Bueno L (1994a) Experimental colitis alters visceromotor response to colorectal distension in awake rats. Dig Dis Sci 39:1239–1248PubMedGoogle Scholar
  181. Morteau O, Julia V, Eeckhout C, Bueno L (1994b) Influence of 5-HT3 receptor antagonists in visceromotor and nociceptive responses to rectal distension before and during experimental colitis in rats. Fundam Clin Pharmacol 8:553–562PubMedGoogle Scholar
  182. Moss NG, Harrington WW, Tucker MS (1997) Pressure, volume, and chemosensitivity in afferent innervation of urinary bladder in rats. Am J Physiol 272:R695–R703PubMedGoogle Scholar
  183. Mukerji G, Yiangou Y, Corcoran SL, Selmer IS, Smith GD, Benham CD, Bountra C, Agarwal SK, Anand P (2006a) Cool and menthol receptor TRPM8 in human urinary bladder disorders and clinical correlations. BMC Urol 6:6–13PubMedGoogle Scholar
  184. Mukerji G, Waters J, Chessell IP, Bountra C, Agarwal SK, Anand P (2006b) Pain during ice water test distinguishes clinical bladder hypersensitivity from overactivity disorders. BMC Urol 6:31–42PubMedGoogle Scholar
  185. Multon S, Schoenen J (2005) Pain control by vagus nerve stimulation: from animal to man… and back. Acta Neurol Belg 105(2):62–67PubMedGoogle Scholar
  186. Nadelhaft I, Booth AM (1984) The location and morphology of preganglionic neurons and the distribution the distribution of the visceral afferents from the rat pelvic nerve: a horseradish peroxidase study. J Comp Neurol 226:238–245PubMedGoogle Scholar
  187. Nadelhaft I, Vera PL (1991) Neurons labelled after the application of tracer to the distal stump of the transected hypogastric nerve in the rat. J Auton Nerv Syst 36:87–96PubMedGoogle Scholar
  188. Nadelhaft I, Roppolo C, Morgan C, De Groat WC (1983) Parasympathetic preganglionic neurons and visceral primary afferents in monkey sacral spinal cord revealed following application of horseradish peroxidase to pelvic nerve. J Comp Neurol 216:36–52PubMedGoogle Scholar
  189. Namasivayam S, Eardley I, Morrison JF (1999) Purinergic sensory neurotransmission in the urinary bladder: an in vitro study in the rat. Br J Urol 854-860Google Scholar
  190. Nazif O, Teichman JM, Gebhart GF (2007) Neural upregulation in interstitial cystitis. Urology 69:24–33PubMedGoogle Scholar
  191. Ness TJ, Gebhart GF (1988) Colorectal distension as a noxious visceral stimulus: physiologic and pharmacologic characterization of pseudaffective reflexes in the rat. Brain Res 450:153–169PubMedGoogle Scholar
  192. Ness TJ, Gebhart GF (1990) Visceral pain: a review of experimental studies. Pain 41:167–234PubMedGoogle Scholar
  193. Ness TJ, Metcalf AM, Gebhart GF (1990) A psychophysical study in humans using phasic colonic distension as a noxious visceral stimulus. Pain 43:377–386PubMedGoogle Scholar
  194. Ness TJ, Fillingim RB, Randich A, Backensto EM, Faught E (2000) Low intensity vagal nerve stimulation lowers human thermal pain thresholds. Pain 86:81–85PubMedGoogle Scholar
  195. Ness TJ, Lewis-Sides A, Castroman P (2001) Characterization of pressor and visceromotor reflex responses to bladder distention in rats: sources of variability and effect of analgesics. J Urol 165:968–975PubMedGoogle Scholar
  196. Okano S, Ikeura Y, Inatomi N (2002) Effects of tachykinin NK1 receptor antagonists on the viscerosensory response caused by colorectal distention in rabbits. J Pharmacol Exp Ther 300:925–931PubMedGoogle Scholar
  197. Olah Z, Karai L, Iadarola MJ (2001) Anandamide activates vanilloid receptor 1 (VR1) at acidic pH in dorsal root ganglia neurons and cells ectopically expressing VR1. J Biol Chem 276:31163–31170PubMedGoogle Scholar
  198. Olivar T, Laird JM (1999) Differential effects of N-methyl-d-aspartate receptor blockade on nociceptive somatic and visceral reflexes. Pain 79:67–73PubMedGoogle Scholar
  199. Ozaki N, Gebhart GF (2001) Characterization of mechanosensitive splanchnic nerve afferent fibers innervating the rat stomach. Am J Physiol 281:G1449–G1459Google Scholar
  200. Ozaki N, Bielefeldt K, Sengupta JN, Gebhart GF (2002) Models of gastric visceral hyperalgesia. Am J Physiol 283:G666–G676Google Scholar
  201. Page AJ, Blackshaw AL (1998) An in vitro study of the properties of vagal afferent fibres innervating the ferret oesophagus and stomach. J Physiol 512:907–916PubMedGoogle Scholar
  202. Page AJ, Blackshaw AL (1999) GABAB receptors inhibit mechanosensitivity of primary afferent endings. J Neurosci 19:8597–8602PubMedGoogle Scholar
  203. Paintal AS (1954) A method of location of the receptors of visceral afferent fibers. J Physiol Lond 124:166–172PubMedGoogle Scholar
  204. Partosoedarso ER, Young RL, Blackshaw AL (2001) GABAB receptors on vagal afferent pathways: peripheral and central inhibition. Am J Physiol Gastrointest Liver Physiol 280:G658–G668PubMedGoogle Scholar
  205. Pascual JI, Insausti R, Gonzalo LM (1989) The pelvic innervation in the rat: different spinal origin and projections in Sprague-Dawley and Wistar rats. Brain Res 480:397–402PubMedGoogle Scholar
  206. Pascual JI, Insausti R, Gonzalo LM (1993) Urinary bladder innervation in male rat: termination of primary afferents in the spinal cord as determined by transganglionic transport of WGA-HRP. J Urol 150:500–504PubMedGoogle Scholar
  207. Pattinson D, Fitzerald M (2004) The neurobiology of infant pain: development of excitatory and inhibitory neurotransmission in the spinal dorsal horn. Reg Anes Pain Med 29:36–44Google Scholar
  208. Peles S, Miranda A, Shaker R, Sengupta JN (2004) Acute nociceptive somatic stimulus sensitizes neurons in the spinal cord to colonic distension in the rat. J Physiol 560:291–302PubMedGoogle Scholar
  209. Pezzone MA, Liang R, Fraser MO (2005) A model of neural cross-talk and irritation in the pelvis: implications for the overlap of chronic pelvic pain disorders. Gastroenterology 128:1953–1964PubMedGoogle Scholar
  210. Phillips RJ, Powley TL (2000) Tension and stretch receptors in gastrointestinal smooth muscle: re-evaluating vagal mechanoreceptor electrophysiology. Brain Res Brain Res Rev 34:1–26PubMedGoogle Scholar
  211. Plotsky PM, Thrivikraman KV, Nemeroff CB, Caldji C, Sharma S, Meaney MJ (2005) Long-term consequences of neonatal rearing on central corticotropin-releasing factor systems in adult male rat offspring. Neuropsychopharmacology 30:2192–204PubMedGoogle Scholar
  212. Price DD, Zhou Q, Moshiree B, Robinson ME, Nicholas Verne G (2006) Peripheral and central contributions to hyperalgesia in irritable bowel syndrome. J Pain 7:529–535PubMedGoogle Scholar
  213. Qin C, Foreman RD (2004) Viscerovisceral convergence of urinary bladder and colorectal inputs to lumbosacral spinal neurons in rats. Neuroreport 15:467–471PubMedGoogle Scholar
  214. Qin C, Malykhina AP, Akbarali HI, Foreman RD (2005) Cross-organ sensitization of lumbosacral spinal neurons receiving urinary bladder input in rats with inflamed colon. Gastroenterology 129:1967–1978PubMedGoogle Scholar
  215. Rachmilewitz D, Simon PL, Schwartz LW, Griswold DE, Fondacaro JD, Wasserman MA (1989) Inflammatory mediators of experimental colitis in rats. Gastroenterology 97:326–337PubMedGoogle Scholar
  216. Randich A, Uzzell T, Cannon R, Ness TJ (2006a) Inflammation and enhanced nociceptive responses to bladder distension produced by intravesical zymosan in the rat. BMC Urol 6:2–8PubMedGoogle Scholar
  217. Randich A, Uzzell T, DeBerry JJ, Cannon R, Ness TJ (2006b) Neonatal urinary bladder inflammation produces adult bladder hypersensitivity. J Pain 7:468–479Google Scholar
  218. Ranieri F, Mei N, Crousillat, J (1973) Splanchnic afferent arising from gastrointestinal and peritoneal mechanoreceptor. Exp Brain Res 16:276–290PubMedGoogle Scholar
  219. Ren K, Randich A, Gebhart GF (1991) Effects of electrical stimulation of vagal afferents on spinothalamic tract cells in the rat. Pain 44:311–319PubMedGoogle Scholar
  220. Ren K, Zhuo M, Randich A, Gebhart GF (1993) Vagal afferent stimulation-produced effects on nociception in capsaicin-treated rats. J Neurophysiol 69(5):1530–1540PubMedGoogle Scholar
  221. Ren TH, Wu J, Yew D, Ziea E, Lao L, Leung WK, Berman B, Hu PJ, Sung JJ (2007) Effects of neonatal maternal separation on neurochemical and sensory response to colonic distension in a rat model of irritable bowel syndrome. Am J Physiol 292:G849–G856Google Scholar
  222. Richter JE, Heading RC, Janssens J, Wilson J (2000) Functional esophageal disorders. In: Drossman DA (ed) Rome II; the functional gastrointestinal disorders, 2nd edn. Degnon, McLean, chap 5Google Scholar
  223. Riley RC, Trafton JA, Chi SI, Basbaum AL (2001) Presynaptic regulation of spinal cord tachykinin signaling via GABAB but not GABAA receptor activation. Neuroscience 103:725–737PubMedGoogle Scholar
  224. Ritchie J (1973) Pain from the pelvic colon by inflating a balloon in the irritable colon syndrome. Gut 14:125–132PubMedGoogle Scholar
  225. Robbins A, Sato Y, Hotta H, Berkley KJ (1990) Responses of hypogastric nerve afferent fibers to uterine distension in estrous or metestrous rats. Neurosci Lett 110:82–85PubMedGoogle Scholar
  226. Robbins A, Berkley KJ, Sato Y (1992) Estrous cycle variation of afferent fibers supplying reproductive organs in the female rat. Brain Res 596:353–356PubMedGoogle Scholar
  227. Rong W, Burnstock G (2004) Activation of ureter nociceptor by exogenous and endogenous ATP in guinea pig. Neuropharmacology 47:1093–1101PubMedGoogle Scholar
  228. Rong W, Spyer KM, Burnstock G (2002) Activation and sensitisation of low and high threshold afferent fibres mediated by P2X receptors in the mouse urinary bladder. J Physiol 541:591–600PubMedGoogle Scholar
  229. Roppolo JR, Tai C, Booth AM, Buffington CA, de Groat WC, Birder LA (2005) Bladder Adelta afferent nerve activity in normal cats and cats with feline interstitial cystitis. J Urol 173(3):1011–1015PubMedGoogle Scholar
  230. Ruch TC (1946) Visceral sensation and referred pain. In: Fulton JF (ed) Howell's textbook of physiology, 15th edn. Saunders, Philadelphia, pp 385–401Google Scholar
  231. Ruch TC (1961) Pathophysiology of pain. In: Ruch TC, Patton JD, Woodbury JW, Towe AL (eds) Medical physiology and biophysics, 9th edn. Saunders, Philadelphia, pp 350–368Google Scholar
  232. Sann H (1998) Chemosensitivity of nociceptive, mechanosensitive afferent nerve fibres in the guinea-pig ureter. Eur J Neurosci 10:1300–1311PubMedGoogle Scholar
  233. Sann H, Hammer K, Hildesheim IF, Pierau FK (1997) Neurons in the chicken ureter are innervated by substance P- and calcitonin gene-related peptide-containing nerve fibres: immunohistochemical and electrophysiological evidence. J Comp Neurol 380:105–118PubMedGoogle Scholar
  234. Schicho R, Waltraud F, Liebmann I, Holzer P, Lippe IT (2004) Increased expression of TRPV1 receptor in dorsal root ganglia by acid insult of the rat gastric mucosa. Eur J Neurosci 19:1811–1818PubMedGoogle Scholar
  235. Schnitzlein HN, Hoffman HH, Tucker CC, Quigley MB (1960) The pelvic splanchnic nerves of the male Rheusus monkey. J Comp Neurol 114:51–65PubMedGoogle Scholar
  236. Schwetz I, McRoberts JA, Coutinho SV, Bradesi S, Gale G, Fanselow M, Million M, Ohning G, Taché Y, Plotsky PM, Mayer EA (2005) Corticotropin-releasing factor receptor 1 mediates acute and delayed stress-induced visceral hyperalgesia in maternally separated Long-Evans rats. Am J Physiol 289:G704–G712Google Scholar
  237. Sedan O, Sprecher E, Yarnitsky D (2005) Vagal stomach afferents inhibit somatic pain perception. Pain 113:354–359PubMedGoogle Scholar
  238. Semenenko FM, Cervero F (1992) Afferent fibres from the guinea-pig ureter: size and peptide content of the dorsal root ganglion cells of origin. Neuroscience 47:197–201PubMedGoogle Scholar
  239. Sengupta JN (2006) Esophageal sensory physiology. In: GI motility online. Nature, New YorkGoogle Scholar
  240. Sengupta JN, Gebhart GF (1994a) Characterization of mechanosensitive pelvic nerve afferent fibers innervating the colon of the rat. J Neurophysiol 71:2046–2060PubMedGoogle Scholar
  241. Sengupta JN, Gebhart GF (1994b) Mechanosensitive properties of pelvic nerve afferent fibers innervating the urinary bladder of the rat. J Neurophysiol 72:2420–30PubMedGoogle Scholar
  242. Sengupta JN, Gebhart GF (1994c) Gastrointestinal afferent fibers and visceral sensations. In: Johnson LR et al (eds) Physiology of the gastrointestinal tract. Raven, New York, pp 483–519Google Scholar
  243. Sengupta JN, Gebhart GF (1998) The sensory innervation of the colon and its modulation. Curr Opin Gastrol 14:15–20Google Scholar
  244. Sengupta JN, Saha JK, Goyal RK (1990) Stimulus-response function studies of esophageal mechanosensitive nociceptor in sympathetic afferents of opossum. J Neurophysiol 64:796–812PubMedGoogle Scholar
  245. Sengupta JN, Saha JK, Goyal RK (1992) Differential sensitivity of bradykinin to esophageal distension-sensitive mechanoreceptor in vagal and sympathetic afferents of the opossum. J Neurophysiol 68:1053–1067PubMedGoogle Scholar
  246. Sengupta JN, Su X, Gebhart GF (1996) Kappa, but not mu or delta, opioids attenuate responses to distention of afferent fibers innervating the rat colon. Gastroenterology 111:968–980PubMedGoogle Scholar
  247. Sengupta JN, Snider A, Su X, Gebhart GF (1999) Effects of kappa opioids in the inflamed rat colon. Pain 79:175–185PubMedGoogle Scholar
  248. Sengupta JN, Medda BK, Shaker R (2002) Effect of GABA(B) receptor agonist on distension-sensitive pelvic nerve afferent fibers innervating rat colon. Am J Physiol 283:G1343–G1351Google Scholar
  249. Shea VK, Cai R, Crepps B, Mason JL, Perl ER (2000) Sensory fibers of the pelvic nerve innervating the Rat's urinary bladder. J Neurophysiol 84:1924–1933PubMedGoogle Scholar
  250. Sheehan D (1932) The afferent nerve supply of the mesentery and significance in the causation of abdominal pain. J Anat 67:233–249Google Scholar
  251. Smid SD, Young RL, Cooper NJ, Blackshaw AL (2001) GABABR expressed on vagal afferent neurons inhibit gastric mechanosensitivity in ferret proximal stomach. Am J Physiol Gastrointest Liver Physiol 281:G1494–G1501PubMedGoogle Scholar
  252. Smith C, Nordstrom E, Sengupta JN, Miranda A (2007) Neonatal gastric suctioning results in chronic somatic and visceral hyperalgesia: role of corticotropin releasing factor. Neurogastroenterol Motil 19:692–699PubMedGoogle Scholar
  253. Sperber AD, Atzmon Y, Neumann L, Weisberg I, Shalit Y, Abu-Shakrah M, Fich A, Buskila D (1999) Fibromyalgia in the irritable bowel syndrome: studies of prevalence and clinical implications. Am J Gastroenterol 94:3541–3546PubMedGoogle Scholar
  254. Spiller R (2007) Recent advances in understanding the role of serotonin in gastrointestinal motility in functional bowel disorders: alterations in 5-HT signalling and metabolism in human disease. Neurogastroenterol Motil 19(Suppl 2):25–31PubMedGoogle Scholar
  255. Strigo IA, Duncan GH, Bushnell MC, Boivin M, Wainer I, Rodriguez Rosas ME, Persson J (2005) The effects of racemic ketamine on painful stimulation of skin and viscera in human subjects. Pain 113:255–264PubMedGoogle Scholar
  256. Su X, Gebhart GF (1998) Mechanosensitive pelvic nerve afferent fibers innervating the colon of the rat polymodal in character. J Neurophysiol 80:2632–2644PubMedGoogle Scholar
  257. Su X, Sengupta JN, Gebhart GF (1997a) Effects of opioids on mechanosensitive pelvic nerve afferent fibers innervating the urinary bladder of the rat. J Neurophysiol 77:1566–1580PubMedGoogle Scholar
  258. Su X, Sengupta JN, Gebhart GF (1997b) Effects of kappa opioid receptor-selective agonists on responses of pelvic nerve afferents to noxious colorectal distension. J Neurophysiol 78:1003–1012PubMedGoogle Scholar
  259. Su X, Joshi SK, Kardos S, Gebhart GF (2002) Sodium channel blocking actions of the kappa-opioid receptor agonist U50,488 contribute to its visceral antinociceptive effects. J Neurophysiol 87:1271–1279PubMedGoogle Scholar
  260. Su X, Riedel ES, Leon LA, Laping NJ (2008) Pharmacologic evaluation of pressor and visceromotor reflex responses to bladder distension. Neurourol Urodyn 27:249–253PubMedGoogle Scholar
  261. Talaat M (1937) Afferent impulses in the nerves supplying the urinary bladder. J Physiol Lond 89:1–13PubMedGoogle Scholar
  262. Talley NJ, Dennis EH, Schettler-Duncan VA, Lacy BE, Olden KW, Crowell MD (2003) Overlapping upper and lower gastrointestinal symptoms in irritable bowel syndrome patients with constipation or diarrhea. Am J Gastroenterol 98:2454–2459PubMedGoogle Scholar
  263. Tang B, Ji Y, Traub RJ (2008) Estrogen alters spinal NMDA receptor activity via a PKA signaling pathway in a visceral pain model in the rat. Pain 137:540–549PubMedGoogle Scholar
  264. Tempest HV, Dixon AK, Turner WH, Elneil S, Sellers LA, Ferguson DR (2004) P2X and P2X receptor expression in human bladder urothelium and changes in interstitial cystitis. BJU Int 93:1344–1348PubMedGoogle Scholar
  265. Thurston CL, Randich A (1992) Electrical stimulation of the subdiaphragmatic vagus in rats: inhibition of heat-evoked responses of spinal dorsal horn neurons and central substrates mediating inhibition of the nociceptive tail flick reflex. Pain 51:349–365PubMedGoogle Scholar
  266. Torrens M, Hald T (1979) Bladder denervation procedures. Urol Clin North Am 6:283–293PubMedGoogle Scholar
  267. Towers S, Princivalle A, Billinton A, Edmunds M, Bettler B, Urban L, Castro-Lopes J, Bowery NG (2000) GABAB receptor protein and mRNA distribution in rat spinal cord and dorsal root ganglia. Eur J Neurosci 12:3201–3210PubMedGoogle Scholar
  268. Traub RJ, Pechman P, Iadarola MJ, Gebhart GF (1992) Fos-like proteins in the lumbosacral spinal cord following noxious and non-noxious colorectal distention in the rat. Pain 49:393–403PubMedGoogle Scholar
  269. Traub RJ, Hutchcroft K, Gebhart GF (1999) The peptide content of colonic afferents decreases following colonic inflammation. Peptides 20:267–273PubMedGoogle Scholar
  270. Traub RJ, Zhai Q, Ji Y, Kovalenko M (2002) NMDA receptor antagonists attenuate noxious and nonnoxious colorectal distention-induced Fos expression in the spinal cord and the visceromotor reflex. Neuroscience 113:205–211PubMedGoogle Scholar
  271. Trevisani M, Patacchini R, Nicoletti P, Gatti R, Gazzieri D, Lissi N, Zagli G, Creminon C, Geppetti P, Harrison S (2005) Hydrogen sulfide causes vanilloid receptor 1-mediated neurogenic inflammation in the airways. Br J Pharmacol 145:1123–1131PubMedGoogle Scholar
  272. Triadafilopoulos G, Simms RW, Goldenberg DL (1991) Bowel dysfunction in fibromyalgia syndrome. Dig Dis Sci 36:59–64PubMedGoogle Scholar
  273. Tsukimi Y, Mizuyachi K, Yamasaki T, Niki T, Hayashi F (2005) Cold response of the bladder in guinea pig: involvement of transient receptor potential channel, TRPM8. Urology 65:406–410PubMedGoogle Scholar
  274. Uemura E, Fletcher TF, Dirks VA, Bradley WE (1973) Distribution of sacral afferent axons in cat urinary bladder. Am J Anat 136:305–313PubMedGoogle Scholar
  275. Uemura E, Fletcher TF, Bradley WE (1974) Distribution of lumbar afferent axons in muscle in muscle coat of cat urinary bladder. Am J Anat 139:389–398Google Scholar
  276. Uemura E, Fletcher TF, Bradley WE (1975) Distribution of lumbar and sacral afferent axons in submucosa of cat urinary bladder. Anat Rec 183:579–587PubMedGoogle Scholar
  277. Ustinova EE, Fraser MO, Pezzone MA (2006) Colonic irritation in the rat sensitizes urinary bladder afferents to mechanical and chemical stimuli: an afferent origin of pelvic organ cross-sensitization. Am J Physiol 290:F1478–F1487Google Scholar
  278. Ustinova EE, Gutkin DW, Pezzone MA (2007) Sensitization of pelvic nerve afferents and mast cell infiltration in the urinary bladder following chronic colonic irritation is mediated by neuropeptides. Am J Physiol 292:F123–F130Google Scholar
  279. Veale D, Kavanagh G, Fielding JF, Fitzeral O (1991) Primary fibromyalgia and the irritable bowel syndrome: different expressions of a common pathogenic process. Br J Rheumatol 30:220–222PubMedGoogle Scholar
  280. Vera PL, Nadelhaft I (1990) Conduction velocity distribution of afferent fibers innervating the rat urinary bladder. Brain Res 520:83–89PubMedGoogle Scholar
  281. Vera PL, Nadelhaft I (1992) Afferent and sympathetic innervation of the dome and the base of the urinary bladder of the female rat. Brain Res 29:651–658Google Scholar
  282. Verne GN, Price DD (2002) Irritable bowel syndrome as a common precipitant of central sensitization. Curr Rheumatol Rep 4:322–328PubMedGoogle Scholar
  283. Verne GN, Robinson ME, Price DD (2001) Hypersensitivity to visceral and cutaneous pain in the irritable bowel syndrome. Pain 93:7–14PubMedGoogle Scholar
  284. Verne GN, Himes NC, Robinson ME, Gopinath KS, Briggs RW, Crosson B, Price DD (2003) Central representation of visceral and cutaneous hypersensitivity in the irritable bowel syndrome. Pain 103:99–110PubMedGoogle Scholar
  285. Von Haller A (1755) A dissertation of the sensible and irritable parts of animals. Nourse, LondonGoogle Scholar
  286. Wallace JL, Le T, Carter L, Appleyard CB, Beck P (1995) Hapten-induced colitis in the rat: alternatives to trinitrobenzene sulfonic acid. J Pharmacol Toxicol Methods 33:237–239PubMedGoogle Scholar
  287. Wang G, Tang B, Traub RJ (2005) Differential processing of noxious colonic input by thoracolumbar and lumbosacral dorsal horn neurons in the rat. J Neurophysiol 94:3788–3794PubMedGoogle Scholar
  288. Wang G, Tang B, Traub RJ (2007) Pelvic nerve input mediates descending modulation of homovisceral processing in the thoracolumbar spinal cord of the rat. Gastroenterology 133:1544–1553PubMedGoogle Scholar
  289. Willert RP, Woolf CJ, Hobson AR, Delaney C, Thompson DG, Aziz Q (2004) The development and maintenance of human visceral pain hypersensitivity is dependent on the N-methyl-d-aspartate receptor. Gastroenterology 126:683–692PubMedGoogle Scholar
  290. Willert RP, Delaney C, Kelly K, Sharma A, Aziz Q, Hobson AR (2007) Exploring the neurophysiological basis of chest wall allodynia induced by experimental oesophageal acidification – evidence of central sensitization. Neurogastroenterol Motil 19:270–278PubMedGoogle Scholar
  291. Williams RE, Hartmann KE, Sandler RS, Miller WC, Steege JF (2004) Prevalence and characteristics of irritable bowel syndrome among women with chronic pelvic pain. Obstet Gynecol 104:452–458PubMedGoogle Scholar
  292. Williams RE, Hartmann KE, Sandler RS, Miller WC, Savitz LA, Steege JF (2005) Recognition and treatment of irritable bowel syndrome among women with chronic pelvic pain. Am J Obstet Gynecol 192:761–767PubMedGoogle Scholar
  293. Winnard KP, Dmitrieva N, Berkley KJ (2006) Cross-organ interactions between reproductive, gastrointestinal, and urinary tracts: modulation by estrous stage and involvement of the hypogastric nerve. Am J Physiol 291(6):R1592–R1601Google Scholar
  294. Winston J, Shenoy M, Medley D, Naniwadekar A, Pasricha PJ (2007) The vanilloid receptor initiates and maintains colonic hypersensitivity induced by neonatal colon irritation in rats. Gastroenterology 132:615–627PubMedGoogle Scholar
  295. Winter DL (1971) Receptor characteristics and conduction velocites in bladder afferents. J Psychiatr Res 8:225–235PubMedGoogle Scholar
  296. Wynn G, Ma B, Ruan HZ, Burnstock G (2004) Purinergic component of mechanosensory transduction is increased in a rat model of colitis. Am J Physiol 287:G647–G657Google Scholar
  297. Xu L, Gebhart GF (2008) Characterization of mouse lumbar splanchnic and pelvic nerve urinary bladder mechanosensory afferents. J Neurophysiol 99:244–253PubMedGoogle Scholar
  298. Xu GY, Shenoy M, Winston JH, Mittal S, Pasricha PJ (2008) P2X receptor-mediated visceral hyperalgesia in a rat model of chronic visceral hypersensitivity. Gut 57(9):1230–1237PubMedGoogle Scholar
  299. Yiangou Y, Facer P, Dyer NHC, Chan CLH, Knowles C, Williams NS, Anand P (2001) Vanilloid receptor 1 immunoreactivity in inflamed human bowel. Lancet 357:1338–1339PubMedGoogle Scholar
  300. Yu Y, de Groat WC (2008) Sensitization of pelvic afferent nerves in the in vitro rat urinary bladder-pelvic nerve preparation by purinergic agonists and cyclophosphamide pretreatment. Am J Physiol Renal Physiol 294:F1146–F1156PubMedGoogle Scholar
  301. Zagorodnyuk VP, Brookes SJH (2000) Transduction sites of vagal mechanoreceptors in the guinea-pig esophagus. J Neurosci 20:6249–6255PubMedGoogle Scholar
  302. Zagorodnyuk VP, Chen BN, Brookes SJ (2001) Intraganglionic laminar endings are mechano-transduction sites of vagal tension receptors in the guinea-pig stomach. J Physiol 534:255–268PubMedGoogle Scholar
  303. Zagorodnyuk VP, Chen BN, Costa M, Brookes SJH (2003) Mechanotransduction by intraganglionic laminar endings of vagal tension receptors in the guinea-pig oesophagus. J Physiol 553:575–587PubMedGoogle Scholar
  304. Zagorodnyuk VP, Lynn P, Costa M, Brookes SJ (2005) Mechanisms of mechanotransduction by specialized low-threshold mechanoreceptors in the guinea pig rectum. Am J Physiol 289:G397–G406Google Scholar
  305. Zagorodnyuk VP, Gibbins IL, Costa M, Brookes SJ, Gregory SJ (2007) Properties of the major classes of mechanoreceptors in the guinea pig bladder. J Physiol 585:147–163PubMedGoogle Scholar
  306. Zamyatina ON (1954) Electrophysiological characteristics and functional significance of afferent impulses originating in the intestinal wall. Transaction of I.P. Pavlov Institute of Physiology 3:193–208Google Scholar
  307. Zhai QZ, Traub RJ (1999) The NMDA receptor antagonist MK-801 attenuates c-Fos expression in the lumbosacral spinal cord following repetitive noxious and non-noxious colorectal distention. Pain 83(2):321–329PubMedGoogle Scholar
  308. Zhou Q, Price DD, Caudle RM, Verne N (2008) Visceral and somatic hypersensitivity in a subset of rats following TNBS-induced colitis. Pain 134:9–15PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  1. 1.Division of Gastroenterology and HepatologyMedical College of WisconsinMilwaukeeUSA

Personalised recommendations