Skip to main content
SpringerLink
Log in

Animal Models of Visceral Pain

  • Protocol
  • First Online:
Animal Models of Pain

Part of the book series: Neuromethods ((NM,volume 49))

  • 1330 Accesses

Abstract

The study of visceral pain is of high clinical relevance and the findings more directly translational in the search for analgesic agents. Early studies of nerve recordings after acute visceral nerve activation with (1) mechanical distension of hollow organs such as the colon or esophagus, (2) chemical irritation, and/or (3) inflammation have provided relevant information about normal, typically silent visceral afferents and evoked behavioral responses. Clinically relevant information about visceral pain has been reported in studies utilizing intact animal models of inflammatory, diabetic, neuropathic, cancer, chemotherapy-induced and other injury-related visceral pain conditions. More recently, animal models designed to study mechanisms signaling the transitional stages from acute to chronic visceral pain are providing information relevant to the development of drug therapies for reducing visceral pain in patients with these conditions. As an example, a visceral pain model of chronic pancreatitis is induced with an alcohol and high-fat diet in rat that persists for 2 months. Increased sensitization, inflammation, and pancreatic tissue disruption typical in the model are reversed by overexpression of met-enkephalin by a herpes simplex viral (HSV) preproenkephalin vector. The therapeutic effects are most likely attributable to opioid receptors located both in the central and peripheral nervous systems, as well as on peripheral cells. Advantages of using (HSV) vectors for therapeutic gene delivery rather than other viral delivery vectors (lentivirus, adenovirus) in certain clinical settings to treat visceral pain are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Aidar O., Geohegan W.A. and Ungewitter L.H. (1952) Splanchnic afferent pathways in the central nervous system. J Neurophysiol 15, 131–8.

    PubMed  CAS  Google Scholar 

  2. Al-Chaer E.D., Feng Y. and Willis W.D. (1999) Comparative study of viscerosomatic input onto postsynaptic dorsal column and spinothalamic tract neurons in the primate. J Neurophysiol 82, 1876–82.

    PubMed  CAS  Google Scholar 

  3. Al-Chaer E.D., Lawand N.B., Westlund K.N. and Willis W.D. (1996) Pelvic visceral input into the nucleus gracilis is largely mediated by the postsynaptic dorsal column pathway. J Neurophysiol 76, 2675–90.

    PubMed  CAS  Google Scholar 

  4. Al-Chaer E.D., Lawand N.B., Westlund K.N. and Willis W.D. (1996) Visceral nociceptive input into the ventral posterolateral nucleus of the thalamus: a new function for the dorsal column pathway. J Neurophysiol 76, 2661–74.

    PubMed  CAS  Google Scholar 

  5. Al-Chaer E.D., Westlund K.N. and Willis W.D. (1996) Potentiation of thalamic responses to colorectal distension by visceral inflammation. NeuroReport 7, 1635–9.

    Article  PubMed  CAS  Google Scholar 

  6. Amassian V.E. (1951) Cortical representation of visceral afferents. J Neurophysiol 14, 433–44.

    PubMed  CAS  Google Scholar 

  7. Amassian V.E. (1951) Fiber groups and spinal pathways of cortically represented visceral afferents. J Neurophysiol 14, 445–60.

    PubMed  CAS  Google Scholar 

  8. Amassian V.E. (1952) Interaction in the somatovisceral projection system. Res Publ Assoc Res Nerv Ment Dis 30, 371–402.

    PubMed  CAS  Google Scholar 

  9. Antonijevic S., Mousa M., Schafer M. and Stein C. (1995) Perineurial defect and peripheral opioid analgesia in inflammation. J Neurosci 15, 165–72.

    PubMed  CAS  Google Scholar 

  10. Avelino A., Cruz F. and Coimbra A. (1997) Sites of renal pain processing in the rat spinal cord. A c-fos study using a percutaneous method to perform ureteral obstruction. J Auton Nerv Syst 67, 60–6.

    Article  PubMed  CAS  Google Scholar 

  11. Barber A. (1993) Mu- and kappa-opioid receptor agonists produce peripheral inhibition of neurogenic plasma extravasation in rat skin. Eur J Pharmacol 236, 113–20.

    Article  PubMed  CAS  Google Scholar 

  12. Barthet M., Dubucquoy L., Garcia S., Gasmi M., Desreumaux P., Colombel J.F., Grimaud J.C., Iovanna J. and Dagorn J.C. (2003) Pancreatic changes in TNBS-induced colitis in mice. Gastroentérol Clin Biol 27, 895–900.

    PubMed  Google Scholar 

  13. Becker R., Sure U. and Bertalanffy H. (1999) Punctate midline myelotomy. A new approach in the management of visceral pain. Acta Neurochir (Wien) 141, 881–3.

    Article  CAS  Google Scholar 

  14. Berkley K.J. and Hubscher C.H. (1995) Are there separate central nervous system pathways for touch and pain? Nat Med 1, 766–73.

    Article  PubMed  CAS  Google Scholar 

  15. Bernard J.F., Huang G.F. and Besson J.M. (1994) The parabrachial area: electrophysiological evidence for an involvement in visceral nociceptive processes. J Neurophysiol 71, 1646–60.

    PubMed  CAS  Google Scholar 

  16. Bielefeldt K., Lamb K. and Gebhart G.F. (2006) Convergence of sensory pathways in the development of somatic and visceral hypersensitivity. Am J Physiol Gastrointest Liver Physiol 291, G658–65.

    Article  PubMed  CAS  Google Scholar 

  17. Binder W., Machelska H., Mousa S., Schmitt T., Riviere P.J., Junien J.L., Stein C. and Schafer M. (2001) Analgesic and antiinflammatory effects of two novel kappa-opioid peptides. Anesthesiology 94, 1034–44.

    Article  PubMed  CAS  Google Scholar 

  18. Bon K., Lanteri-Minet M., Michiels J.F. and Menetrey D. (1998) Cyclophosphamide cystitis as a model of visceral pain in rats: a c-fos and Krox-24 study at telencephalic levels, with a note on pituitary adenylate cyclase activating polypeptide (PACAP). Exp Brain Res 122, 165–74.

    Article  PubMed  CAS  Google Scholar 

  19. Bonica J.J. (1990) Evolution and current status of pain programs. J Pain Symptom Manage 5, 368–74.

    Article  PubMed  CAS  Google Scholar 

  20. Boyle D.L., Moore J., Yang L., Sorkin L.S. and Firestein G.S. (2002) Spinal adenosine receptor activation inhibits inflammation and joint destruction in rat adjuvant-induced arthritis. Arthritis Rheum 46, 3076–82.

    Article  PubMed  CAS  Google Scholar 

  21. Braz J., Beaufour C., Coutaux A., Epstein A.L., Cesselin F., Hamon M. and Pohl M. (2001) Therapeutic efficacy in experimental polyarthritis of viral-driven enkephalin overproduction in sensory neurons. J Neurosci 21, 7881–8.

    PubMed  CAS  Google Scholar 

  22. Bueno L., Fioramonti J., Delvaux M. and Frexinos J. (1997) Mediators and pharmacology of visceral sensitivity: from basic to clinical investigations. Gastroenterology 112, 1714–43.

    Article  PubMed  CAS  Google Scholar 

  23. Buffington C.A. (2001) Visceral pain in humans: lessons from animals. Curr Pain Headache Rep 5, 44–51.

    Article  PubMed  CAS  Google Scholar 

  24. Burton E.A., Wechuck J.B., Wendell S.K., Goins W.F., Fink D.J. and Glorioso J.C. (2001) Multiple applications for replication-defective herpes simplex virus vectors. Stem Cells 19, 358–77.

    Article  PubMed  CAS  Google Scholar 

  25. Cameron D.M., Brennan T.J. and Gebhart G.F. (2008) Hind paw incision in the rat produces long-lasting colon hypersensitivity. J Pain 9, 246–53.

    Article  PubMed  Google Scholar 

  26. Cervero F. and Laird J.M. (1999) Visceral pain. Lancet 353, 2145–8.

    Article  PubMed  CAS  Google Scholar 

  27. Cervero F. and Sann H. (1989) Mechanically evoked responses of afferent fibers innervation the guinea-pig’s ureter: an in vitro study. J Physiol 412, 245–266.

    Google Scholar 

  28. Cervero F., Laird J.M. and Pozo M.A. (1992) Selective changes of receptive field properties of spinal nociceptive neurones induced by noxious visceral stimulation in the cat. Pain 51, 335–42.

    Article  PubMed  CAS  Google Scholar 

  29. Christianson J.A., Liang R., Ustinova E.E., Davis B.M., Fraser M.O. and Pezzone M.A. (2007) Convergence of bladder and colon sensory innervation occurs at the primary afferent level. Pain 128, 235–43.

    Article  PubMed  Google Scholar 

  30. Cooperman A.M. (1981) Chronic pancreatitis. Surg Clin North Am 61, 71–83.

    PubMed  CAS  Google Scholar 

  31. Danielson P.B. and Dores R.M. (1999) Molecular evolution of the opioid/orphanin gene family. Gen Comp Endocrinol 113, 169–86.

    Article  PubMed  CAS  Google Scholar 

  32. de Groat W.C. (1987) Neuropeptides in pelvic afferent pathways. Experientia 43, 801–13.

    Article  PubMed  Google Scholar 

  33. Detakats G. and Walter L. (1947) The treatment of pancreatic pain by splanchnic nerve section. Surg Gynecol Obstet, 85, 742–6.

    CAS  Google Scholar 

  34. Dinis P., Charrua A., Avelino A. and Cruz F. (2004) Intravesical resiniferatoxin decreases spinal c-fos expression and increases bladder volume to reflex micturition in rats with chronic inflamed urinary bladders. BJU Int 94, 153–7.

    Article  PubMed  Google Scholar 

  35. Feng Y., Cui M., Al-Chaer E.D. and Willis W.D. (1998) Epigastric antinociception by cervical dorsal column lesions in rats. Anesthesiology 89, 411–20.

    Article  PubMed  CAS  Google Scholar 

  36. Ferreira S.H., Romitelli M. and de Nucci G. (1989) Endothelin-1 participation in overt and inflammatory pain. J Cardiovasc Pharmacol 13, Suppl 5, S220–2.

    Article  PubMed  CAS  Google Scholar 

  37. Foitzik T., Eibl G., Hotz H.G., Faulhaber J., Kirchengast M. and Buhr H.J. (2000) Endothelin receptor blockade in severe acute pancreatitis leads to systemic enhancement of microcirculation, stabilization of capillary permeability, and improved survival rates. Surgery 128, 399–407.

    Article  PubMed  CAS  Google Scholar 

  38. Fujii Y., Toyooka H. and Tanaka H. (1998) Efficacy of thoracic epidural analgesia following laparoscopic cholecystectomy. Eur J Anaesthesiol 15, 342–4.

    Article  PubMed  CAS  Google Scholar 

  39. Giamberardino M.A., Valente R., de Bigontina P. and Vecchiet L. (1995) Artificial ureteral calculosis in rats: behavioural characterization of visceral pain episodes and their relationship with referred lumbar muscle hyperalgesia. Pain 61, 459–69.

    Article  PubMed  CAS  Google Scholar 

  40. Giamberardino M.A., Valente R., Affaitati G. and Vecchiet L. (1997) Central neuronal changes in recurrent visceral pain. Int J Clin Pharmacol Res 17, 63–6.

    PubMed  CAS  Google Scholar 

  41. Gildenberg P.L. and Hirshberg R.M. (1984) Limited myelotomy for the treatment of intractable cancer pain. J Neurol Neurosurg Psychiatry 47, 94–6.

    Article  PubMed  CAS  Google Scholar 

  42. Gorbitz C. and Leavens M.E. (1971) Alcohol block of the celiac plexus for control of upper abdominal pain caused by cancer and pancreatitis. Technical note. J Neurosurg 34, 575–9.

    Article  PubMed  CAS  Google Scholar 

  43. Green P.G. and Levine J.D. (1992) Delta- and kappa-opioid agonists inhibit plasma extravasation induced by bradykinin in the knee joint of the rat. Neuroscience 49, 129–33.

    Article  PubMed  CAS  Google Scholar 

  44. Häbler H-.J., Jänig W. and Koltzenburg M. (1990) Activation of unmyelinated afferent fibres by mechanical stimuli and inflammation of the urinary bladder in the cat. J Physiol 425, 545–62.

    PubMed  Google Scholar 

  45. Häbler H.J., Janig W. and 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, 449–60.

    PubMed  Google Scholar 

  46. Haley J.E. and Wilcox G.L. (1992) Involvement of excitatory amino acids and peptides in the spinal mechanisms underlying hyperalgesia. In: Hyperalgesia and Allodynia (ed. by Willis WD, Jr.), pp. 281–94. Raven, New York.

    Google Scholar 

  47. Head H. (1893) On disturbances of sensation with special reference to the pain of visceral disease. Brain 16, 1–133.

    Article  Google Scholar 

  48. Hegyi P., Rakonczay Z., Jr., Sari R., Gog C., Lonovics J., Takacs T. and Czako L.L. (2004). Arginine-induced experimental pancreatitis. World J Gastroenterol 10, 2003–9.

    PubMed  CAS  Google Scholar 

  49. Hirshberg R.M., Al-Chaer E.D., Lawand N.B., Westlund K.N. and Willis W.D. (1996) Is there a pathway in the posterior funiculus that signals visceral pain? Pain 67, 291–305.

    Article  PubMed  CAS  Google Scholar 

  50. Hoogerwerf W.A., Zou L., Shenoy M., Sun D., Micci M.A., Lee-Hellmich H., Xiao S.Y., Winston J.H. and Pasricha P.J. (2001) The proteinase-activated receptor 2 is involved in nociception. J Neurosci 21, 9036–42.

    PubMed  CAS  Google Scholar 

  51. Hong Y. and Abbott F.V. (1995) Peripheral opioid modulation of pain and inflammation in the formalin test. Eur J Pharmacol 277, 21–8.

    Article  PubMed  CAS  Google Scholar 

  52. Houghton A.K., Kadura S. and Westlund K.N. (1997) Dorsal column lesions reverse the reduction of homecage activity in rats with pancreatitis. NeuroReport 8, 3795–800.

    Article  PubMed  CAS  Google Scholar 

  53. Houghton A.K., Wang C.C. and Westlund K.N. (2001) Do nociceptive signals from the pancreas travel in the dorsal column? Pain 89, 207–20.

    Article  PubMed  CAS  Google Scholar 

  54. Hurwitz A. and Gurwitz J. (1950) Relief of pain in chronic relapsing pancreatitis by unilateral sympathectomy. Arch Surg 61, 379–86.

    Article  PubMed  CAS  Google Scholar 

  55. Jagger S.I., Scott H. and Rice A. (1999) Inflammation of the rat urinary bladder is associated with a referred thermal hyperalgesia which is nerve growth factor dependent. Br J Anaesth 83, 442–9.

    Article  Google Scholar 

  56. Jasmin L., Burkey A.R., Card J.P. and Basbaum A.I. (1997) Transneuronal labeling of a nociceptive pathway, the spino-(trigemino-)parabrachio-amygdaloid, in the rat. J Neurosci 17, 3751–65.

    PubMed  CAS  Google Scholar 

  57. Jasmin L., Janni G., Manz H.J. and Rabkin S.D. (1998) Activation of CNS circuits producing a neurogenic cystitis: evidence for centrally induced peripheral inflammation. J Neurosci 18, 10016–29.

    PubMed  CAS  Google Scholar 

  58. Joris J., Costello A., Dubner R. and Hargreaves K.M. (1990) Opiates suppress carrageenan-induced edema and hyperthermia at doses that inhibit hyperalgesia. Pain 43, 95–103.

    Article  PubMed  CAS  Google Scholar 

  59. Katter J.T., Dado R.J., Kostarczyk E. and Giesler G.J., Jr. (1996) Spinothalamic and spinohypothalamic tract neurons in the sacral spinal cord of rats. II. Responses to cutaneous and visceral stimuli. J Neurophysiol 75, 2606–28.

    PubMed  CAS  Google Scholar 

  60. Kim Y.S. and Kwon S.J. (2000) High thoracic midline dorsal column myelotomy for severe visceral pain due to advanced stomach cancer. Neurosurgery 46, 85–90.

    Article  PubMed  CAS  Google Scholar 

  61. Kimball E.S., Palmer J.M., D’Andrea M.R., Hornby P.J. and Wade P.R. (2005) Acute colitis induction by oil of mustard results in later development of an IBS-like accelerated upper GI transit in mice. Am J Physiol Gastrointest Liver Physiol 288, G1266–73.

    Article  PubMed  CAS  Google Scholar 

  62. Kloppel G. (1990) Pathology of chronic pancreatitis and pancreatic pain. Acta Chir Scand 156, 261–5.

    PubMed  CAS  Google Scholar 

  63. Kress K. and Reeh P.W. (1996) Chemical excitation and sensitization in nociceptors. In: Neurobiology of Nociceptors (ed. by Belemonte C, Cervero F), pp. 258–97. Oxford University Press, New York.

    Google Scholar 

  64. Laird J.M., Martinez-Caro L., Garcia-Nicas E. and Cervero F. (2001) A new model of visceral pain and referred hyperalgesia in the mouse. Pain 92, 335–42.

    Article  PubMed  CAS  Google Scholar 

  65. Laird J.M., Roza C. and Cervero F. (1997) Effects of artificial calculosis on rat ureter motility: peripheral contribution to the pain of ureteric colic. Am J Physiol 272, R1409–16.

    PubMed  CAS  Google Scholar 

  66. Lamigeon C., Bellier J.P., Sacchettoni S., Rujano M. and Jacquemont B. (2001) Enhanced neuronal protection from oxidative stress by coculture with glutamic acid decarboxylase-expressing astrocytes. J Neurochem 77, 598–606.

    Article  PubMed  CAS  Google Scholar 

  67. Lanteri-Minet M., Bon K., de Pommery J., Michiels J.F. and Menetrey D. (1995) Cyclophosphamide cystitis as a model of visceral pain in rats: model elaboration and spinal structures involved as revealed by the expression of c-Fos and Krox-24 proteins. Exp Brain Res 105, 220–32.

    Article  PubMed  CAS  Google Scholar 

  68. Lanteri-Minet M., Isnardon P., de Pommery J. and Menetrey D. (1993) Spinal and hindbrain structures involved in visceroception and visceronociception as revealed by the expression of Fos, Jun and Krox-24 proteins. Neuroscience 55, 737–53.

    Article  PubMed  CAS  Google Scholar 

  69. Lim R.K., Miller D.G., Guzman F., Rodgers D.W., Rogers R.W., Wang S.K., Chao P.Y. and Shih T.Y. (1967) Pain and analgesia evaluated by the intraperitoneal bradykinin-evoked pain method in man. Clin Pharmacol Ther 8, 521–42.

    PubMed  CAS  Google Scholar 

  70. Longhurst J.C., Kaufman M.P., Ordway G.A. and Musch T.I. (1984) Effects of bradykinin and capsaicin on endings of afferent fibers from abdominal visceral organs. Am J Physiol 247, R552–9.

    PubMed  CAS  Google Scholar 

  71. Lu Y., McNearney T.A., Lin W., Wilson S.P., Yeomans D.C. and Westlund K.N. (2007) Treatment of inflamed pancreas with enkephalin encoding HSV-1 recombinant vector reduces inflammatory damage and behavioral sequelae. Mol Ther 15, 1812–9.

    Article  PubMed  CAS  Google Scholar 

  72. Lu Y., McNearney T.A., Wilson S.P., Yeomans D.C. and Westlund K.N. (2008) Joint capsule treatment with enkephalin-encoding HSV-1 recombinant vector reduces inflammatory damage and behavioural sequelae in rat CFA monoarthritis. Eur J Neurosci 27, 1153–65.

    Article  PubMed  Google Scholar 

  73. Mackenzie K.A. (1909) XXIII. Resection of the sciatic nerve: neuroplasty: end results. Ann Surg 50, 295–312.

    Article  PubMed  CAS  Google Scholar 

  74. Mayer E.A. and Gebhart G.F. (1994) Basic and clinical aspects of visceral hyperalgesia. Gastroenterology 107, 271–93.

    PubMed  CAS  Google Scholar 

  75. McMahon S.B. (1997) Are there fundamental differences in the peripheral mechanisms of visceral and somatic pain? Behav Brain Sci 20, 381–91; discussion 435–513.

    Google Scholar 

  76. McMahon S.B. and Abel C. (1987) A model for the study of visceral pain states: chronic inflammation of the chronic decerebrate rat urinary bladder by irritant chemicals. Pain 28, 109–27.

    Article  PubMed  CAS  Google Scholar 

  77. McMahon S.B., Dmitrieva N. and Koltzenburg M. (1995) Visceral pain. Br J Anaesth 75, 132–44.

    Article  PubMed  CAS  Google Scholar 

  78. McNeill D.L. and Burden H.W. (1986) Convergence of sensory processes from the heart and left ulnar nerve onto a single afferent perikaryon: a neuroanatomical study in the rat employing fluorescent tracers. Anat Rec 214, 441–4.

    Article  PubMed  CAS  Google Scholar 

  79. Menetrey D., Gannon A., Levine J.D. and Basbaum A.I. (1989) Expression of c-fos protein in interneurons and projection neurons of the rat spinal cord in response to noxious somatic, articular, and visceral stimulation. J Comp Neurol 285, 177–95.

    Article  PubMed  CAS  Google Scholar 

  80. Merkord J. and Hennighausen G. (1989) Acute pancreatitis and bile duct lesions in rat induced by dibutyltin dichloride. Exp Pathol 36, 59–62.

    Article  PubMed  CAS  Google Scholar 

  81. Merkord J., Jonas L., Weber H., Kroning G., Nizze H. and Hennighausen G. (1997) Acute interstitial pancreatitis in rats induced by dibutyltin dichloride (DBTC): pathogenesis and natural course of lesions. Pancreas 15, 392–401.

    Article  PubMed  CAS  Google Scholar 

  82. Michaelis M., Häbler H.J. and Jäenig W. (1996) Silent afferents: a separate class of primary afferents? Clin Exp Pharmacol Physiol 23, 99–105.

    Google Scholar 

  83. Minter R.M., Ferry M.A., Murday M.E., Tannahill C.L., Bahjat F.R., Oberholzer C., Oberholzer A., LaFace D., Hutchins B., Wen S., Shinoda J., Copeland E.M., 3 rd and Moldawer L.L. (2001) Adenoviral delivery of human and viral IL-10 in murine sepsis. J Immunol 167, 1053–9.

    PubMed  CAS  Google Scholar 

  84. Murphy A.Z., Suckow S.K., Johns M. and Traub R.J. (2009) Sex differences in the activation of the spinoparabrachial circuit by visceral pain. Physiol Behav 97(2), 205–12.

    Article  PubMed  CAS  Google Scholar 

  85. Nauta H.J., Hewitt E., Westlund K.N. and Willis W.D., Jr. (1997) Surgical interruption of a midline dorsal column visceral pain pathway. Case report and review of the literature. J Neurosurg 86, 538–42.

    Article  PubMed  CAS  Google Scholar 

  86. Nauta H.J., Soukup V.M., Fabian R.H., Lin J.T., Grady J.J., Williams C.G., Campbell G.A., Westlund K.N. and Willis W.D., Jr. (2000) Punctate midline myelotomy for the relief of visceral cancer pain. J Neurosurg 92, 125–30.

    PubMed  CAS  Google Scholar 

  87. Ness T.J. and Gebhart G.F. (1991) Interactions between visceral and cutaneous nociception in the rat. II. Noxious visceral stimuli inhibit cutaneous nociceptive neurons and reflexes. J Neurophysiol 66, 29–39.

    PubMed  CAS  Google Scholar 

  88. Ness T.J. and Gebhart G.F. (1988) Colorectal distension as a noxious visceral stimulus: physiologic and pharmacologic characterization of pseudaffective reflexes in the rat. Brain Res 450, 153–69.

    Article  PubMed  CAS  Google Scholar 

  89. Ness T.J. and Gebhart G.F. (2000) Acute inflammation differentially alters the activity of two classes of rat spinal visceral nociceptive neurons. Neurosci Lett 281, 131–4.

    Article  PubMed  CAS  Google Scholar 

  90. Ness T.J., Richter H.E., Varner R.E. and Fillingim R.B. (1998) A psychophysical study of discomfort produced by repeated filling of the urinary bladder. Pain 76, 61–9.

    Google Scholar 

  91. NIH (1998) NIH Guide: New Directions in Pain Research I. URL http://grants.nih.gov/grants/guide/pa-files/PA-98-102.html.

  92. Noble M.D., Romac J., Vigna S.R. and Liddle R.A. (2008) A pH-sensitive, neurogenic pathway mediates disease severity in a model of post-ERCP pancreatitis. Gut 57, 1566–71.

    Article  PubMed  CAS  Google Scholar 

  93. Olivar T., Cervero F. and Laird J.M. (2000) Responses of rat spinal neurones to natural and electrical stimulation of colonic afferents: effect of inflammation. Brain Res 866, 168–77.

    Google Scholar 

  94. Ordway G.A., Longhurst J.C. and Mitchell J.H. (1983) Stimulation of pancreatic afferents reflexly activates the cardiovascular system in cats. Am J Physiol 245, R820–6.

    PubMed  CAS  Google Scholar 

  95. Ordway G.A., Mitchell J.H. and Longhurst J.C. (1982) Bradykinin stimulates pancreatic afferents to activate the cardiovascular system. Trans Assoc Am Physicians 95, 229–36.

    PubMed  CAS  Google Scholar 

  96. Palecek J., Paleckova V. and Willis W.D. (2003) Fos expression in spinothalamic and postsynaptic dorsal column neurons following noxious visceral and cutaneous stimuli. Pain 104, 249–57.

    Article  PubMed  CAS  Google Scholar 

  97. Peters C.M., Lindsay T.H., Pomonis J.D., Luger N.M., Ghilardi J.R., Sevcik M.A. and Mantyh P.W. (2004) Endothelin and the tumorigenic component of bone cancer pain. Neuroscience 126, 1043–52.

    Article  PubMed  CAS  Google Scholar 

  98. Pomonis J.D., Rogers S.D., Peters C.M., Ghilardi J.R. and Mantyh P.W. (2001) Expression and localization of endothelin receptors: implications for the involvement of peripheral glia in nociception. J Neurosci 21, 999–1006.

    PubMed  CAS  Google Scholar 

  99. Puig-Divi V., Molero X., Salas A., Guarner F., Guarner L. and Malagelada J.R. (1996) Induction of chronic pancreatic disease by trinitrobenzene sulfonic acid infusion into rat pancreatic ducts. Pancreas 13, 417–24.

    Article  PubMed  CAS  Google Scholar 

  100. Puig-Divi V., Molero X., Vaquero E., Salas A., Guarner F. and Malagelada J. (1999) Ethanol feeding aggravates morphological and biochemical parameters in experimental chronic pancreatitis. Digestion 60, 166–74.

    Article  PubMed  CAS  Google Scholar 

  101. Plusczyk T., Bersal B., Westermann S., Menger M. and Feifel G. (1999) ET-1 induces pancreatitis like microvascular deterioration and acinar cell injury. J Surg Res 85, 301–10.

    Article  PubMed  CAS  Google Scholar 

  102. Plusczyk T., Witzel B., Menger M.D. and Schilling M. (2003) ETA and ETB receptor function in pancreatitis-associated microcirculatory failure, inflammation, and parenchymal injury. Am J Physiol Gastrointest Liver Physiol 285, G145–53.

    PubMed  CAS  Google Scholar 

  103. Qin C. and Foreman R.D. (2004) Viscerovisceral convergence of urinary bladder and colorectal inputs to lumbosacral spinal neurons in rats. NeuroReport 15, 467–71.

    Article  PubMed  Google Scholar 

  104. Rack F.J. and Elkins C.W. (1950) Experiences with vagotomy and sympathectomy in the treatment of chronic recurrent pancreatitis. AMA Arch Surg 61, 937–43.

    Article  PubMed  CAS  Google Scholar 

  105. Ray B.S. and Neill C.L. (1947) Abdominal visceral sensation in man. Ann Surg 126, 709–24.

    Article  Google Scholar 

  106. Ren Y., Zhang L., Lu Y., Yang H., Westlund K.N. (2009) Central lateral thalamic neurons receive noxious visceral mechanical and chemical input in rats. J Neurophysiol 102, 244–58.

    Google Scholar 

  107. Rigamonti D.D. and Hancock M.B. (1974) Analysis of field potentials elicited in the dorsal column nuclei by splanchnic nerve A-beta afferents. Brain Res 77, 326–9.

    Article  PubMed  CAS  Google Scholar 

  108. Rigamonti D.D. and Hancock M.B. (1978) Viscerosomatic convergence in the dorsal column nuclei of the cat. Exp Neurol 61, 337–48.

    Article  PubMed  CAS  Google Scholar 

  109. Rodella L., Rezzani R., Gioia M., Tredici G. and Bianchi R. (1998) Expression of Fos immunoreactivity in the rat supraspinal regions following noxious visceral stimulation. Brain Res Bull 47, 357–66.

    Article  PubMed  CAS  Google Scholar 

  110. Roza C., Laird J.M. and Cervero F. (1998) Spinal mechanisms underlying persistent pain and referred hyperalgesia in rats with an experimental ureteric stone. J Neurophysiol 79, 1603–12.

    PubMed  CAS  Google Scholar 

  111. Roza C. and Reeh P.W. (2001) Substance P, calcitonin gene related peptide and PGE2 co-released from the mouse colon: a new model to study nociceptive and inflammatory responses in viscera, in vitro. Pain. 93, 213–9.

    Google Scholar 

  112. Ruch T.C. (1947) Visceral sensation and referred pain. In: Howell’s Textbook of Physiology, 15th ed. (ed. by Fulton JF), pp. 385–401. Saunders, Philadelphia.

    Google Scholar 

  113. Ruda M.A. and Dubner R. (1992) Molecular and biochemical events mediate neuronal plasticity following inflammation and hyperalgesia. In: Hyperalgesia and Allodynia (ed. by Willis WD, Jr.), pp. 311–26. Raven, New York.

    Google Scholar 

  114. Saban M.R., Nguyen N.B., Hammond T.G. and Saban R. (2002) Gene expression profiling of mouse bladder inflammatory responses to LPS, substance P, and antigen-stimulation. Am J Pathol 160, 2095–110.

    Google Scholar 

  115. Salzet M. (2001) Neuroimmunology of opioids from invertebrates to human. Neuro Endocrinol Lett 22, 467–74.

    PubMed  CAS  Google Scholar 

  116. Schaible H.G. and Schmidt R.F. (1983) Activation of groups III and IV sensory units in medial articular nerve by local mechanical stimulation of knee joint. J Neurophysiol 49, 35–44.

    Google Scholar 

  117. Schmidt J., Compton C.C., Rattner D.W., Lewandrowski K. and Warshaw A.L. (1995) Late histopathologic changes and healing in an improved rodent model of acute necrotizing pancreatitis. Digestion 56, 246–52.

    Article  PubMed  CAS  Google Scholar 

  118. Schmidt J., Rattner D.W., Lewandrowski K., Compton C.C., Mandavilli U., Knoefel W.T. and Warshaw A.L. (1992) A better model of acute pancreatitis for evaluating therapy. Ann Surg 215, 44–56.

    Article  PubMed  CAS  Google Scholar 

  119. Sengupta J.N. and Gebhart G.F. (1994) Characterization of mechanosensitive pelvic nerve afferent fibers innervating the colon of the rat. J Neurophysiol 71, 2046–60.

    PubMed  CAS  Google Scholar 

  120. Sevcik M.A., Jonas B.M., Lindsay T.H., Halvorson K.G., Ghilardi J.R., Kuskowski M.A., Mukherjee P., Maggio J.E. and Mantyh P.W. (2006) Endogenous opioids inhibit early-stage pancreatic pain in a mouse model of pancreatic cancer. Gastroenterology 131, 900–10.

    Article  PubMed  CAS  Google Scholar 

  121. Sharkey K.A., Williams R.G. and Dockray G.J. (1984) Sensory substance P innervation of the stomach and pancreas. Demonstration of capsaicin-sensitive sensory neurons in the rat by combined immunohistochemistry and retrograde tracing. Gastroenterology 87, 914–21.

    PubMed  CAS  Google Scholar 

  122. Sinclair D., Wedell H. and Feindel W. (1948) Referred pain and associated phenomena. Brain 71, 184–211.

    Article  PubMed  CAS  Google Scholar 

  123. Sparmann G., Merkord J., Jaschke A., Nizze H., Jonas L., Lohr M., Liebe S. and Emmrich J. (1997) Pancreatic fibrosis in experimental pancreatitis induced by dibutyltin dichloride. Gastroenterology 112, 1664–72.

    Article  PubMed  CAS  Google Scholar 

  124. Stein C. (1995) The control of pain in peripheral tissue by opioids. N Engl J Med 332, 1685–90.

    Article  PubMed  CAS  Google Scholar 

  125. Steiner I., Spivack J.G., Deshmane S.L., Ace C.I., Preston C.M. and Fraser N.W. (1990) A herpes simplex virus type 1 mutant containing a nontransinducing Vmw65 protein establishes latent infection in vivo in the absence of viral replication and reactivates efficiently from explanted trigeminal ganglia. J Virol 64, 1630–8.

    PubMed  CAS  Google Scholar 

  126. Stone H.H. and Chauvin E.J. (1990) Pancreatic denervation for pain relief in chronic alcohol associated pancreatitis. Br J Surg 77, 303–5.

    Article  PubMed  CAS  Google Scholar 

  127. Sugiura Y., Terui N. and Hosoya Y. (1989) Difference in distribution of central terminals between visceral and somatic unmyelinated (C) primary afferent fibers. J Neurophysiol 62, 834–40.

    PubMed  CAS  Google Scholar 

  128. Taylor B.K., Peterson M.A., Roderick R.E., Tate J., Green P.G., Levine J.O. and Basbaum A.I. (2000) Opioid inhibition of formalin-induced changes in plasma extravasation and local blood flow in rats. Pain 84, 263–70.

    Article  PubMed  CAS  Google Scholar 

  129. Traub R.J. (2000) Evidence for thoracolumbar spinal cord processing of inflammatory, but not acute colonic pain. Neuroreport 11, 2113–6.

    Article  PubMed  CAS  Google Scholar 

  130. Traub R.J., Pechman P., Iadarola M.J. and Gebhart G.F. (1992) Fos-like proteins in the lumbosacral spinal cord following noxious and non-noxious colorectal distention in the rat. Pain 49, 393–403.

    Article  PubMed  CAS  Google Scholar 

  131. Traub R.J., Silva E., Gebhart G.F. and Solodkin A. (1996) Noxious colorectal distention induced-c-Fos protein in limbic brain structures in the rat. Neurosci Lett 215, 165–8.

    Article  PubMed  CAS  Google Scholar 

  132. Ustinova E.E., Fraser M.O. and Pezzone M.A. (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 Renal Physiol 290, F1478–87.

    Article  PubMed  CAS  Google Scholar 

  133. Vera-Portocarrero L.P., Lu Y. and Westlund K.N. (2003) Nociception in persistent pancreatitis in rats: effects of morphine and neuropeptide alterations. Anesthesiology 98, 474–84.

    Article  PubMed  CAS  Google Scholar 

  134. Vizzard M.A. (2000) Increased expression of spinal cord Fos protein induced by bladder stimulation after spinal cord injury. Am J Physiol Regul Integr Comp Physiol 279, R295–305.

    PubMed  CAS  Google Scholar 

  135. Walker J.S. (2003) Anti-inflammatory effects of opioids. Adv Exp Med Biol 521, 148–60.

    PubMed  CAS  Google Scholar 

  136. Wang C.C. and Westlund K.N. (2001) Responses of rat dorsal column neurons to pancreatic nociceptive stimulation. Neuro-Report 12, 2527–30.

    Article  PubMed  CAS  Google Scholar 

  137. Wang C.C., Willis W.D. and Westlund K.N. (1999) Ascending projections from the area around the spinal cord central canal: a Phaseolus vulgaris leucoagglutinin study in rats. J Comp Neurol 415, 341–67.

    Article  PubMed  CAS  Google Scholar 

  138. Wesselmann U., Czakanski P.P., Affaitati G. and Giamberardino M.A. (1998) Uterine inflammation as a noxious visceral stimulus: behavioral characterization in the rat. Neurosci Lett 246, 73–6.

    Google Scholar 

  139. Westlund K.N. (2009) Gene therapy for pancreatitis pain. Gene Ther 16, 483–92.

    Article  PubMed  CAS  Google Scholar 

  140. Westlund, K.N., Vera- Portocarrero L.P., Zhang L., Wei J., Quast M.J., Palmer S.N. and Cleeland C.S. (2009) fMRI of supraspinal areas after morphine and one week pancreatic inflammation. NeuroImage 44, 23–34.

    Article  PubMed  Google Scholar 

  141. Wick E.C., Hoge S.G., Grahn S.W., Kim E., Divino L.A., Grady E.F., Bunnett N.W. and Kirkwood K.S. (2006) Transient receptor potential vanilloid 1, calcitonin gene-related peptide, and substance P mediate nociception in acute pancreatitis. Am J Physiol Gastrointest Liver Physiol 290, G959–69.

    Article  PubMed  CAS  Google Scholar 

  142. Wilson S.P. and Yeomans D.C. (2000) Genetic therapy for pain management. Curr Rev Pain 4, 445–50.

    Article  PubMed  CAS  Google Scholar 

  143. Wilson S.P. and Yeomans D.C. (2002) Virally mediated delivery of enkephalin and other neuropeptide transgenes in experimental pain models. Ann N Y Acad Sci 971, 515–21.

    Article  PubMed  CAS  Google Scholar 

  144. Wilson S.P., Yeomans D.C., Bender M.A., Lu Y., Goins W.F. and Glorioso J.C. (1999) Antihyperalgesic effects of infection with a preproenkephalin-encoding herpes virus. Proc Natl Acad Sci USA 96, 3211–6.

    Article  PubMed  CAS  Google Scholar 

  145. Winfree C.J., Coombs D.W., DeLeo J.A. and Colburn R.W. (1992) Analgesic effects of intrathecally-administered 3 alpha-hydroxy-5 alpha-pregnan-20-one in a rat mechanical visceral pain model. Life Sci 50,1007–12.

    Article  PubMed  CAS  Google Scholar 

  146. Wolfe D., Wechuck J., Krisky D., Mata M. and Fink D.J. (2009) A clinical trial of gene therapy for chronic pain. Pain Med 10, 1325–30.

    Article  PubMed  Google Scholar 

  147. Wu T.T., Su Y.H., Block T.M. and Taylor J.M. (1998) Atypical splicing of the latency-associated transcripts of herpes simplex type 1. Virology 243, 140–9.

    Article  PubMed  CAS  Google Scholar 

  148. Yang H., McNearney T.A., Chu R., Lu Y., Ren Y., Yeomans D.C., Wilson S.P. and Westlund K.N. (2008) Enkephalin-encoding herpes simplex virus-1 decreases inflammation and hotplate sensitivity in a chronic pancreatitis model. Mol Pain 4, 8.

    Article  PubMed  CAS  Google Scholar 

  149. Yoshimura N. and de Groat W.C. (1999) Increased excitability of afferent neurons innervating rat urinary bladder after chronic bladder inflammation. J Neurosci 19, 4644–53.

    PubMed  CAS  Google Scholar 

  150. Yotsumoto F., Manabe T. and Ohshio G. (1993) Bradykinin involvement in the aggravation of acute pancreatitis in rabbits. Digestion 54, 224–30.

    Article  PubMed  Google Scholar 

  151. Zhang H.Q., Rong P.J., Zhang S.P., Al-Chaer E.D. and Willis W.D. (2003) Noxious visceral inputs enhance cutaneous tactile response in rat thalamus. Neurosci Lett 336, 109–12.

    Article  PubMed  CAS  Google Scholar 

  152. Zhou L., Zhang Q., Stein C. and Schafer M. (1998) Contribution of opioid receptors on primary afferent versus sympathetic neurons to peripheral opioid analgesia. J Pharmacol Exp Ther 286, 1000–6.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The work described in this chapter was carried out in collaboration with Drs. Ying Lu and Louis Vera-Portocarrero whose contributions are gratefully acknowledged. The technical contribution of Sarah Abshire to the chapter reference formatting and behavioral studies in the high-fat and alcohol pancreatitis study is also gratefully acknowledged. Research support was provided by NIH grant NS039041.

Author information

Authors and Affiliations

  1. Department of Physiology, University of Kentucky Medical Center, Lexington, KY, USA

    Karin N. Westlund

Authors
  1. Karin N. Westlund
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. , Department of Anesthesiology, Yale University School of Medicine, Cedar Street 333, New Haven, 06520-8051, Connecticut, USA

    Chao Ma

  2. College of Medicine, Department of Anesthesiology, University of Cincinnati, Albert Sabin Way 231, Cincinnati, 45267-0531, Ohio, USA

    Jun-Ming Zhang

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Westlund, K.N. (2011). Animal Models of Visceral Pain. In: Ma, C., Zhang, JM. (eds) Animal Models of Pain. Neuromethods, vol 49. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-880-5_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-60761-880-5_3

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-879-9

  • Online ISBN: 978-1-60761-880-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation