• 1
    Dery O, Corvera CU, Steinhoff M, Bunnett NW. Proteinase-activated receptors: novel mechanisms of signaling by serine proteases. Am J Physiol 1998; 274: C142952.
  • 2
    Cenac N, Garcia-Villar R, Ferrier L et al. Proteinase-activated receptor-2-induced colonic inflammation in mice: possible involvement of afferent neurons, nitric oxide, and paracellular permeability. J Immunol 2003; 170: 4296300.
  • 3
    Cenac N, Coelho AM, Nguyen C et al. Induction of intestinal inflammation in mouse by activation of proteinase-activated receptor-2. Am J Pathol 2002; 161: 190315.
  • 4
    Cenac N, Garcia-Villar R, Mazelin L et al. Activation of proteinase-activated receptor-2 by the peptide SLIGRL or trypsin induces inflammation of mouse colon. Gastroenterology 2001; 120: A725.
  • 5
    Coelho AM, Guiard B, Garcia-Villar R et al. Proteinase-activated receptor-2 (PAR-2) activation produces delayed rectal hyperalgesia in awake rats. Gastroenterology 2001; 120: A178.
  • 6
    Nguyen C, Coelho AM, Grady E et al. Colitis induced by proteinase-activated receptor-2 agonists is mediated by a neurogenic mechanism. Can J Physiol Pharmacol 2003; 81: 9207.
  • 7
    Reed DE, Barajas-Lopez C, Cottrell G et al. Mast cell tryptase and proteinase-activated receptor 2 induce hyperexcitability of guinea-pig submucosal neurons. J Physiol Lond 2003; 547: 53142.
  • 8
    Kawao N, Ikeda H, Kitano T et al. Modulation of capsaicin-evoked visceral pain and referred hyperalgesia by protease-activated receptors 1 and 2. J Pharmacol Sci 2004; 94: 27785.
  • 9
    Coelho AM, Vergnolle N, Guiard B, Fioramonti J, Bueno L. Proteinases and proteinase-activated receptor 2: a possible role to promote visceral hyperalgesia in rats. Gastroenterology 2002; 122: 103547.
  • 10
    van der Merwe JQ, Ohland CL, Hirota CL, MacNaughton WK. Prostaglandin E-2 derived from cyclooxygenases 1 and 2 mediates intestinal epithelial ion transport stimulated by the activation of protease-activated receptor 2. J Pharmacol Exp Ther 2009; 329: 74752.
  • 11
    van der Merwe JQ, Hollenberg MD, MacNaughton WK. EGF receptor transactivation and MAP kinase mediate proteinase-activated receptor-2-induced chloride secretion in intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol 2008; 294: G44151.
  • 12
    Jarry A, Dorso L, Gratio V et al. PAR-2 activation increases human intestinal mucin secretion through EGFR transactivation. Biochem Biophys Res Commun 2007; 364: 68994.
  • 13
    Cuffe JE, Bertog M, Velazquez-Rocha S, Dery O, Bunnett N, Korbmacher C. Basolateral PAR-2 receptors mediate KCl secretion and inhibition of Na+ absorption in the mouse distal colon. J Physiol Lond 2002; 539: 20922.
  • 14
    Mall M, Gonska T, Thomas J, Hirtz S, Schreiber R, Kunzelmann K. Activation of ion secretion via proteinase-activated receptor-2 in human colon. Am J Physiol Gastrointest Liver Physiol 2002; 282: G20010.
  • 15
    Mule F, Baffi MC, Falzone M, Cerra MC. Signal transduction pathways involved in the mechanical responses to protease-activated receptors in rat colon. J Pharmacol Exp Ther 2002; 303: 126572.
  • 16
    Mule F, Baffi MC, Cerra MC. Dual effect mediated by protease-activated receptors on the mechanical activity of rat colon. Br J Pharmacol 2002; 136: 36774.
  • 17
    Bian ZX, Li Z, Huang ZX et al. Unbalanced expression of protease-activated receptors-1 and-2 in the colon of diarrhea-predominant irritable bowel syndrome patients. J Gastroenterol 2009; 44: 66674.
  • 18
    Kayssi A, Amadesi S, Bautista F, Bunnett NW, Vanner S. Mechanisms of protease-activated receptor 2-evoked hyperexcitability of nociceptive neurons innervating the mouse colon. J Physiol Lond 2007; 580: 97791.
  • 19
    Kayssi A, Karanjia R, Bunnett N, Vanner S. Activation of proteinase activated receptor 2 (PAR-2) on nociceptive mouse colonic dorsal root ganglia (DRG) neurons evokes prolonged hyperexcitability and modulates underlying ion channels. Gastroenterology 2005; 128: A222.
  • 20
    Cenac N, Andrews CN, Holzhausen M et al. Role for protease activity in visceral pain in irritable bowel syndrome. J Clin Invest 2007; 117: 63647.
  • 21
    Gecse K, Roka R, Ferrier L et al. Increased faecal serine protease activity in diarrhoeic IBS patients: a colonic lumenal factor impairing colonic permeability and sensitivity. Gut 2008; 57: 5919.
  • 22
    King CD, Wong F, Currie T, Mauderli AP, Fillingim RB, Riley JL III. Deficiency in endogenous modulation of prolonged heat pain in patients with irritable bowel syndrome and temporomandibular disorder. Pain 2009; 143: 1728.
  • 23
    Price DD, Craggs JG, Zhou QQ, Verne GN, Perlstein WM, Robinson ME. Widespread hyperalgesia in irritable bowel syndrome is dynamically maintained by tonic visceral impulse input and placebo/nocebo factors: evidence from human psychophysics, animal models, and neuroimaging. Neuroimage 2009; 47: 9951001.
  • 24
    Verne GN, Robinson ME, Vase L, Price DD. Reversal of visceral and cutaneous hyperalgesia by local rectal anesthesia in irritable bowel syndrome (IBS) patients. Pain 2003; 105: 22330.
  • 25
    Zhou QQ, Fillingim RB, Riley JL, Malarkey WB, Verne GN. Central and peripheral hypersensitivity in the irritable bowel syndrome. Pain 2010; 148: 45461.
  • 26
    Zhou QQ, Fillingim RB, Riley JL, Verne GN. Thermal hypersensitivity in a subset of irritable bowel syndrome patients. World J Gastroenterol 2009; 15: 325460.
  • 27
    Dai Y, Moriyama T, Higashi T et al. Proteinase-activated receptor 2-mediated potentiation of transient receptor potential vanilloid subfamily 1 activity reveals a mechanism for proteinase-induced inflammatory pain. J Neurosci 2004; 24: 42939.
  • 28
    Suckow SK, Caudle RM. NMDA receptor subunit expression and PAR2 receptor activation in colospinal afferent neurons (CANs) during inflammation induced visceral hypersensitivity. Mol Pain 2009; 5: 54.
  • 29
    Suckow SK, Caudle RM. Identification and immunohistochemical characterization of colospinal afferent neurons in the rat. Neuroscience 2008; 153: 80313.
  • 30
    Karai L, Brown DC, Mannes AJ et al. Deletion of vanilloid receptor 1-expressing primary afferent neurons for pain control. J Clin Invest 2004; 113: 134452.
  • 31
    Ness TJ, Gebhart GF. Colorectal distension as a noxious visceral stimulus: physiologic and pharmacologic characterization of pseudaffective reflexes in the rat. Brain Res 1988; 450: 15369.
  • 32
    Wesselmann U, Czakanski PP, Affaitati G, Giamberardino MA. Uterine inflammation as a noxious visceral stimulus: behavioral characterization in the rat. Neurosci Lett 1998; 246: 736.
  • 33
    Zhou Q, Price DD, Caudle RM, Verne GN. Visceral and somatic hypersensitivity in a subset of rats following TNBS-induced colitis. Pain 2008; 134: 915.
  • 34
    Harrison JS, McSwiney BA. The chemical transmitter of motor impulses to the stomach. J Physiol 1936; 87: 7986.
  • 35
    Paton WD, Zar MA. The origin of acetylcholine released from guinea-pig intestine and longitudinal muscle strips. J Physiol 1968; 194: 1333.
  • 36
    Ward SM, Bayguinov J, Won KJ, Grundy D, Berthoud HR. Distribution of the vanilloid receptor (VR1) in the gastrointestinal tract. J Comp Neurol 2003; 465: 12135.
  • 37
    Matsumoto K, Kurosawa E, Terui H et al. Localization of TRPV1 and contractile effect of capsaicin in mouse large intestine: high abundance and sensitivity in rectum and distal colon. Am J Physiol Gastrointest Liver Physiol 2009; 297: G34860.
  • 38
    Matsumoto K, Hosoya T, Tashima K, Namiki T, Murayama T, Horie S. Distribution of transient receptor potential vanilloid 1 channel-expressing nerve fibers in mouse rectal and colonic enteric nervous system: relationship to peptidergic and nitrergic neurons. Neuroscience 2011; 172: 51834.
  • 39
    van den Wijngaard RM, Klooker TK, Welting O et al. Essential role for TRPV1 in stress-induced (mast cell-dependent) colonic hypersensitivity in maternally separated rats. Neurogastroenterol Motil 2009; 21: 11071e94.
  • 40
    Christianson JA, McIlwrath SL, Koerber HR, Davis BM. Transient receptor potential vanilloid 1-immunopositive neurons in the mouse are more prevalent within colon afferents compared to skin and muscle afferents. Neuroscience 2006; 140: 24757.
  • 41
    Jones RC III, Xu L, Gebhart GF. 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 2005; 25: 109819.
  • 42
    Miranda A, Nordstrom E, Mannem A, Smith C, Banerjee B, Sengupta JN. The role of transient receptor potential vanilloid 1 in mechanical and chemical visceral hyperalgesia following experimental colitis. Neuroscience 2007; 148: 102132.
  • 43
    Qin HY, Luo JL, Qi SD, Xu HX, Sung JJ, Bian ZX. Visceral hypersensitivity induced by activation of transient receptor potential vanilloid type 1 is mediated through the serotonin pathway in rat colon. Eur J Pharmacol 2010; 647: 7583.
  • 44
    Winston J, Shenoy M, Medley D, Naniwadekar A, Pasricha PJ. The vanilloid receptor initiates and maintains colonic hypersensitivity induced by neonatal colon irritation in rats. Gastroenterology 2007; 132: 61527.
  • 45
    Hayashi K, Shibata C, Nagao M et al. Intracolonic capsaicin stimulates colonic motility and defecation in conscious dogs. Surgery 2010; 147: 78997.
  • 46
    Arendt-Nielsen L, Schipper KP, Dimcevski G et al. Viscero-somatic reflexes in referred pain areas evoked by capsaicin stimulation of the human gut. Eur J Pain 2008; 12: 54451.
  • 47
    Drewes AM, Schipper KP, Dimcevski G et al. Gut pain and hyperalgesia induced by capsaicin: a human experimental model. Pain 2003; 104: 33341.
  • 48
    Lynn PA, Blackshaw LA. In vitro recordings of afferent fibres with receptive fields in the serosa, muscle and mucosa of rat colon. J Physiol Lond 1999; 518: 27182.
  • 49
    Song XY, Chen BN, Zagorodnyuk VP et al. Identification of medium/high-threshold extrinsic mechanosensitive afferent nerves to the gastrointestinal tract. Gastroenterology 2009; 137: 27484.
  • 50
    Brierley SM, Carter R, Jones W et al. Differential chemosensory function and receptor expression of splanchnic and pelvic colonic afferents in mice. J Physiol Lond 2005; 567: 26781.