Research Article| Volume 97, ISSUE 1, P19-25, April 18, 2002

Sensitization of enteric reflexes in the rat colon in vitro


      We have investigated sensitization of reflexes in the isolated rat colon in order to develop a model that might prove useful for investigating how the sensitivity of enteric reflexes can be altered by prior stimulation. Records were taken of circular muscle tension, 7–10 mm oral and anal to radial distension exerted by a hook passed through the wall of the colon. A test stimulus of 1.5 g produced consistent contractions both oral and anal to the distension. A conditioning protocol, consisting of repeated application of 3 g for 30 s with 30 s between the stimuli for 30 min, doubled the amplitudes of reflex contractions that were evoked by the test stimuli but did not change the sensitivity of the muscle to the direct action of carbachol. The enhanced responses persisted for at least 40 min. The enhancement of reflexes was not reduced by antagonists of tachykinin NK3 receptors or of 5-HT3 receptors, but the reflex oral to stimulation was reduced by NK1 and NK3 antagonists added together. Sensitization was abolished by the cyclo-oxygenase and thromboxane synthase inhibitor, indomethacin. We conclude that sensitization can be reliably induced in vitro and that the model described in the present work can be used to investigate drugs that interfere with the sensitization process.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Autonomic Neuroscience: Basic and Clinical
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Alex G.
        • Kunze W.A.A.
        • Furness J.B.
        • Clerc N.
        Comparison of the effects of neurokinin-3 receptor blockade on two forms of slow synaptic transmission in myenteric AH neurons.
        Neuroscience. 2001; 104: 263-269
        • Baxendale A.
        • Bountra C.
        • Clayton N.
        • et al.
        Irritable bowel syndrome as visceral hyperalgesia: implications for therapy?.
        Curr. Opin. CPNS Invest. Drugs. 1999; 1: 86-97
        • Buéno L.
        • Fioramonti J.
        • Delvaux M.
        • Frexinos J.
        Mediators and pharmacology of visceral sensitivity: from basic to clinical investigations.
        Gastroenterology. 1997; 112: 1714-1743
        • Camilleri M.
        • Choi M.G.
        Review article: irritable bowel syndrome.
        Aliment. Pharmacol. Ther. 1997; 11: 3-15
        • Clerc N.
        • Furness J.B.
        • Kunze W.A.A.
        • Thomas E.A.
        • Bertrand P.P.
        Long-term effects of synaptic activation at low frequency on excitability of myenteric AH neurons.
        Neuroscience. 1999; 90: 279-289
        • Costa M.
        • Furness J.B.
        The peristaltic reflex: an analysis of nerve pathways and their pharmacology.
        Naunyn-Schmiedeberg's Arch. Pharmacol. 1976; 294: 47-60
        • Costa M.
        • Cuello A.C.
        • Furness J.B.
        • Franco R.
        Distribution of enteric neurons showing immunoreactivity for substance P in the guinea pig ileum.
        Neuroscience. 1980; 5: 323-331
        • Couture R.
        • Toma N.
        • Barbot L.
        SR142801 behaves as a tachykinin NK-3 receptor agonist on a spinal nociceptive reflex in the rat.
        Life Sci. 2000; 66: 51-65
        • Dekkers J.A.
        • Akkermans L.M.
        • Kroese A.B.
        Effects of the inflammatory mediator prostaglandin E2 on myenteric neurons in guinea pig ileum.
        Am. J. Physiol. 1997; 272: G1451-G1456
        • Franck H.
        • Kong I.D.
        • Shuttleworth C.W.
        • Sanders K.M.
        Rebound excitation and alternating slow wave patterns depend upon eicosanoid production in canine proximal colon.
        J. Physiol. 1999; 520: 885-895
        • Gay J.
        • Fioramonti J.
        • Garcia-Villar R.
        • Buéno L.
        Alterations of intestinal motor responses to various stimuli after Nippostrongylus brasiliensis infection in rats: role of mast cells.
        Neurogastroenterol. Motil. 2000; 12: 207-214
        • Holzer P.
        Ascending enteric reflex: multiple neurotransmitter systems and interactions.
        Am. J. Physiol. 1989; 256: 540-545
        • Jenkinson K.M.
        • Morgan J.M.
        • Furness J.B.
        • Southwell B.R.
        Neurons bearing NK3 tachykinin receptors revealed by specific binding of fluorescently labelled agonists in the guinea pig ileum.
        Histochem. Cell Biol. 1999; 112: 233-246
        • Kunze W.A.A.
        • Furness J.B.
        The enteric nervous system and regulation of intestinal motility.
        Annu. Rev. Physiol. 1999; 61: 117-142
        • Kunze W.A.A.
        • Bornstein J.C.
        • Furness J.B.
        Identification of sensory nerve cells in a peripheral organ, the intestine of a mammal.
        Neuroscience. 1995; 66: 1-4
        • Lomax A.E.G.
        • Bertrand P.P.
        • Furness J.B.
        Identification of the populations of enteric neurons that have NK1 tachykinin receptors in the guinea pig small intestine.
        Cell Tissue Res. 1998; 294: 27-33
        • Mann P.T.
        • Southwell B.R.
        • Ding Y.Q.
        • Shigemoto R.
        • Mizuno N.
        • Furness J.B.
        Localization of neurokinin 3 (NK3) receptor immunoreactivity in the rat gastrointestinal tract.
        Cell Tissue Res. 1997; 289: 1-9
        • Mawe G.M.
        Tachykinins as mediators of slow EPSPs in guinea pig gall bladder ganglia: involvement of neurokinin-3 receptors.
        J. Physiol. (London). 1995; 485: 513-524
        • Mayer E.A.
        • Raybould H.E.
        Role of visceral afferent mechanisms in functional bowel disorders.
        Gastroenterology. 1990; 99: 1688-1704
        • McLean P.G.
        • Garcia Villar R.
        • Fioramonti J.
        • Buéno L.
        Effects of tachykinin receptor antagonists on the rat jejunal distension pain response.
        Eur. J. Pharmacol. 1998; 345: 247-252
        • Munakata J.
        • Naliboff B.
        • Harraf F.
        • et al.
        Repetitive sigmoid stimulation induces rectal hyperalgesia in patients with irritable bowel syndrome.
        Gastroenterology. 1997; 112: 55-63
        • Neunlist M.
        • Dobreva G.
        • Schemann M.
        Characteristics of mucosally projecting myenteric neurons in the guinea pig proximal colon.
        J. Physiol. (London). 1999; 517: 533-546
        • Serra J.
        • Azpiroz F.
        • Malagelada J.R.
        Perception and reflex responses to intestinal distention in humans are modified by simultaneous or previous stimulation.
        Gastroenterology. 1995; 109: 1742-1749
        • Sundler F.
        • Håkanson R.
        • Larsson L.I.
        • Brodin E.
        • Nilsson G.
        Substance P in the gut: an immunochemical and immunohistochemical study of its distribution and development.
        in: Von Euler U.S. Substance P. Raven Press, New York1977: 59-65
        • Waterman S.A.
        • Costa M.
        • Tonini M.
        Accommodation mediated by enteric inhibitory reflexes in the isolated guinea pig small intestine.
        J. Physiol. (Lond.). 1994; 474: 539-546