Randomized clinical trial: inhibition of the TRPV1 system in patients with nonerosive gastroesophageal reflux disease and a partial response to PPI treatment is not associated with analgesia to esophageal experimental pain

References

• Fass R. Erosive esophagitis and nonerosive reflux disease (NERD): comparison of epidemiologic, physiologic, and therapeutic characteristics. J Clin Gastroenterol 2007;41:131–7.
   PubMed Web of Science ®Google Scholar
• Fass R, Sifrim D. Management of heartburn not responding to proton pump inhibitors. Gut 2009;58:295–309.
   PubMed Web of Science ®Google Scholar
• Drewes AM, Reddy H, Pedersen J, Funch-Jensen P, Gregersen H, Arendt-Nielsen L. Multimodal pain stimulations in patients with grade B oesophagitis. Gut 2006;55:926–32.
   PubMed Web of Science ®Google Scholar
• Fass R, Naliboff B, Higa L, Johnson C, Kodner A, Munakata J, Differential effect of long-term esophageal acid exposure on mechanosensitivity and chemosensitivity in humans. Gastroenterology 1998;115:1363–73.
   PubMed Web of Science ®Google Scholar
• Reddy H, Staahl C, Arendt-Nielsen L, Gregersen H, Drewes AM, Funch-Jensen P. Sensory and biomechanical properties of the esophagus in non-erosive reflux disease. Scand J Gastroenterol 2007;42:432–40.
   PubMed Web of Science ®Google Scholar
• Holzer P. Taste receptors in the gastrointestinal tract. V. Acid sensing in the gastrointestinal tract. Am J Physiol Gastrointest Liver Physiol 2007;292:G699–705.
   PubMed Web of Science ®Google Scholar
• Patapoutian A, Tate S, Woolf CJ. Transient receptor potential channels: targeting pain at the source. Nat Rev Drug Discov 2009;8:55–68.
   PubMed Web of Science ®Google Scholar
• Gunthorpe MJ, Chizh BA. Clinical development of TRPV1 antagonists: targeting a pivotal point in the pain pathway. Drug Discov Today 2009;14:56–67.
   PubMed Web of Science ®Google Scholar
• Guarino MP, Cheng L, Ma J, Harnett K, Biancani P, Altomare A, Increased TRPV1 gene expression in esophageal mucosa of patients with non-erosive and erosive reflux disease. Neurogastroenterol Motil 2010;22:746–51, e219.
   PubMed Web of Science ®Google Scholar
• Blackshaw LA, Page AJ, Partosoedarso ER. Acute effects of capsaicin on gastrointestinal vagal afferents. Neuroscience 2000;96:407–16.
   PubMed Web of Science ®Google Scholar
• Rong W, Hillsley K, Davis JB, Hicks G, Winchester WJ, Grundy D. Jejunal afferent nerve sensitivity in wild-type and TRPV1 knockout mice. J Physiol 2004;560:867–81.
   Google Scholar
• Chung G, Jung SJ, Oh SB. The transient receptor potential (TRP) family in pain and temperature sensation. In Beaulieu P, Lussier D, Porreca F, Dickenson A, editors. Pharmacology of pain. Seattle: IASP Press; 2010. pp 327.
   Google Scholar
• Chizh BA, O'Donnell MB, Napolitano A, Wang J, Brooke AC, Aylott MC, The effects of the TRPV1 antagonist SB-705498 on TRPV1 receptor-mediated activity and inflammatory hyperalgesia in humans. Pain 2007;132:132–41.
   PubMed Web of Science ®Google Scholar
• Gavva NR, Treanor JJ, Garami A, Fang L, Surapaneni S, Akrami A, Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked hyperthermia in humans. Pain 2008;136:202–10.
   PubMed Web of Science ®Google Scholar
• Staahl C, Olesen AE, Andresen T, Arendt-Nielsen L, Drewes AM. Assessing efficacy of non-opioid analgesics in experimental pain models in healthy volunteers: an updated review. Br J Clin Pharmacol 2009;68:322–41.
   PubMedGoogle Scholar
• Arendt-Nielsen L, Olesen AE, Staahl C, Menzaghi F, Kell S, Wong GY, Analgesic efficacy of peripheral kappa-opioid receptor agonist CR665 compared to oxycodone in a multi-modal, multi-tissue experimental human pain model: selective effect on visceral pain. Anesthesiology 2009;111:616–24.
   PubMed Web of Science ®Google Scholar
• Drewes AM, Schipper KP, Dimcevski G, Petersen P, Andersen OK, Gregersen H, Multimodal assessment of pain in the esophagus: a new experimental model. Am J Physiol Gastrointest Liver Physiol 2002;283:G95–103.
   PubMed Web of Science ®Google Scholar
• Krarup AL, Ny L, Astrand M, Bajor A, Hvid-Jensen F, Hansen MB, Randomised clinical trial: the efficacy of a transient receptor potential vanilloid 1 antagonist AZD1386 in human oesophageal pain. Aliment Pharmacol Ther 2011;33:1113–22.
   PubMed Web of Science ®Google Scholar
• Olesen AE, Staahl C, Brock C, Arendt-Nielsen L, Drewes AM. Evoked human oesophageal hyperalgesia: a potential tool for analgesic evaluation? Basic Clin Pharmacol Toxicol 2009;105:126–36.
   PubMed Web of Science ®Google Scholar
• Staahl C, Christrup LL, Andersen SD, Arendt-Nielsen L, Drewes AM. A comparative study of oxycodone and morphine in a multi-modal, tissue-differentiated experimental pain model. Pain 2006;123:28–36.
   PubMed Web of Science ®Google Scholar
• Shaw MJ, Talley NJ, Beebe TJ, Rockwood T, Carlsson R, Adlis S, Initial validation of a diagnostic questionnaire for gastroesophageal reflux disease. Am J Gastroenterol 2001;96:52–7.
   PubMed Web of Science ®Google Scholar
• Quiding H, Webster L, Jonzon B, Effects of the TRPV1 Antagonist AZD1386 in patients with pain after third molar extraction. 13th World Congress on Pain; Montreal; 2010. p PH 373.
   Google Scholar
• Krarup AL, Simren M, Funch-Jensen P, Hansen MB, Hvid-Jensen F, Brun J, The esophageal multimodal pain model: normal values and degree of sensitization in healthy young male volunteers. Dig Dis Sci 2011;56:1967–75.
   PubMed Web of Science ®Google Scholar
• Olesen SS, Olesen AE, Gravesen F, Poulsen JL, Funch-Jensen P, Gregersen H, An endoscopic method for thermal and chemical stimulation of the human oesophagus. Neurogastroenterol Motil 2009;21:1250–e116.
   PubMedGoogle Scholar
• Staahl C, Reddy H, Andersen SD, Arendt-Nielsen L, Drewes AM. Multi-modal and tissue-differentiated experimental pain assessment: reproducibility of a new concept for assessment of analgesics. Basic Clin Pharmacol Toxicol 2006;98:201–11.
   PubMed Web of Science ®Google Scholar
• Drewes AM, Gregersen H, Arendt-Nielsen L. Experimental pain in gastroenterology: a reappraisal of human studies. Scand J Gastroenterol 2003;38:1115–30.
   PubMed Web of Science ®Google Scholar
• Brock C, Andresen T, Frøkjaer JB, Gale J, Olesen AE, Arendt-Nielsen L, Central pain mechanisms following combined acid and capsaicin perfusion of the human oesophagus. Eur J Pain 2010;14:273–81.
   PubMedGoogle Scholar
• Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 2000;288:306–13.
   PubMed Web of Science ®Google Scholar
• Kandulski A, Malfertheiner P. GERD in 2010: diagnosis, novel mechanisms of disease and promising agents. Nat Rev Gastroenterol Hepatol 2011;8:73–4.
   PubMed Web of Science ®Google Scholar
• Szallasi A, Blumberg PM. Vanilloid (Capsaicin) receptors and mechanisms. Pharmacol Rev 1999;51:159–212.
   PubMed Web of Science ®Google Scholar
• Davis JB, Gray J, Gunthorpe MJ, Hatcher JP, Davey PT, Overend P, Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature 2000;405:183–7.
   PubMed Web of Science ®Google Scholar
• Levine JD, Alessandri-Haber N. TRP channels: targets for the relief of pain. Biochim Biophys Acta 2007;1772:989–1003.
   PubMed Web of Science ®Google Scholar
• Pedersen J, Reddy H, Funch-Jensen P, Arendt-Nielsen L, Gregersen H, Drewes AM. Cold and heat pain assessment of the human oesophagus after experimental sensitisation with acid. Pain 2004;110:393–9.
   PubMed Web of Science ®Google Scholar
• Willert RP, Hobson AR, Delaney C, Hicks KJ, Dewit OE, Aziz Q. Neurokinin-1 receptor antagonism in a human model of visceral hypersensitivity. Aliment Pharmacol Ther 2007;25:309–16.
   PubMedGoogle Scholar
• Fujino K, de la Fuente SG, Takami Y, Takahashi T, Mantyh CR. Attenuation of acid induced oesophagitis in VR-1 deficient mice. Gut 2006;55:34–40.
   PubMedGoogle Scholar
• Wickenden AD, Chaplan SR. Once is not enough: improved efficacy following repeated dosing with a TRPV1 antagonist. Pain 2009;142:5–6.
   PubMedGoogle Scholar
• Xu H, Ramsey IS, Kotecha SA, Moran MM, Chong JA, Lawson D, TRPV3 is a calcium-permeable temperature-sensitive cation channel. Nature 2002;418:181–6.
   PubMed Web of Science ®Google Scholar
• Bolcskei K, Helyes Z, Szabo A, Sándor K, Elekes K, Németh J, Investigation of the role of TRPV1 receptors in acute and chronic nociceptive processes using gene-deficient mice. Pain 2005;117:368–76.
   PubMed Web of Science ®Google Scholar
• Cavanaugh DJ, Lee H, Lo L, Shields SD, Zylka MJ, Basbaum AI, Distinct subsets of unmyelinated primary sensory fibers mediate behavioral responses to noxious thermal and mechanical stimuli. Proc Natl Acad Sci USA 2009;106:9075–80.
   PubMed Web of Science ®Google Scholar
• Pogatzki-Zahn EM, Shimizu I, Caterina M, Raja SN. Heat hyperalgesia after incision requires TRPV1 and is distinct from pure inflammatory pain. Pain 2005;115:296–307.
   PubMedGoogle Scholar
• Szabo A, Helyes Z, Sandor K, Bite A, Pintér E, Németh J, Role of transient receptor potential vanilloid 1 receptors in adjuvant-induced chronic arthritis: in vivo study using gene-deficient mice. J Pharmacol Exp Ther 2005;314:111–19.
   PubMed Web of Science ®Google Scholar
• van den Wijngaard RM, Klooker TK, Welting O, Stanisor OI, Wouters MM, van der Coelen D, Essential role for TRPV1 in stress-induced (mast cell-dependent) colonic hypersensitivity in maternally separated rats. Neurogastroenterol Motil 2009;21:1107–e94.
   PubMed Web of Science ®Google Scholar