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TRPV1 sensitization mediates postinflammatory visceral pain following acute colitis.

Abstract

Quiescent phases of inflammatory bowel disease (IBD) are often accompanied by chronic abdominal pain. Although the transient receptor potential vanilloid 1 (TRPV1) ion channel has been postulated as an important mediator of visceral hypersensitivity, its functional role in postinflammatory pain remains elusive. This study aimed at establishing the role of TRPV1 in the peripheral sensitization underlying chronic visceral pain in the context of colitis. Wild-type and TRPV1-deficient mice were separated into three groups (control, acute colitis, and recovery), and experimental colitis was induced by oral administration of dextran sulfate sodium (DSS). Recovery mice showed increased chemically and mechanically evoked visceral hypersensitivity 5 wk post-DSS discontinuation, at which point inflammation had completely resolved. Significant changes in nonevoked pain-related behaviors could also be observed in these animals, indicative of persistent discomfort. These behavioral changes correlated with elevated colonic levels of substance P (SP) and TRPV1 in recovery mice, thus leading to the hypothesis that SP could sensitize TRPV1 function. In vitro experiments revealed that prolonged exposure to SP could indeed sensitize capsaicin-evoked currents in both cultured neurons and TRPV1-transfected human embryonic kidney (HEK) cells, a mechanism that involved TRPV1 ubiquitination and subsequent accumulation at the plasma membrane. Importantly, although TRPV1-deficient animals experienced similar disease severity and pain as wild-type mice in the acute phase of colitis, TRPV1 deletion prevented the development of postinflammatory visceral hypersensitivity and pain-associated behaviors. Collectively, our results suggest that chronic exposure of colon-innervating primary afferents to SP could sensitize TRPV1 and thus participate in the establishment of persistent abdominal pain following acute inflammation.

Authors+Show Affiliations

Department of Physiology and Pharmacology, Inflammation Research Network, University of Calgary, Calgary, Alberta, Canada;Institut National de la Santé et de la Recherche Medicale (INSERM), Toulouse, France; Le Centre National de la Recherche Scientifique (CNRS), Toulouse, France; and Université de Toulouse III Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France.Department of Physiology and Pharmacology, Inflammation Research Network, University of Calgary, Calgary, Alberta, Canada;Department of Physiology and Pharmacology, Inflammation Research Network, University of Calgary, Calgary, Alberta, Canada;Department of Physiology and Pharmacology, Inflammation Research Network, University of Calgary, Calgary, Alberta, Canada;Institut National de la Santé et de la Recherche Medicale (INSERM), Toulouse, France; Le Centre National de la Recherche Scientifique (CNRS), Toulouse, France; and Université de Toulouse III Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France.Department of Physiology and Pharmacology, Inflammation Research Network, University of Calgary, Calgary, Alberta, Canada; Institut National de la Santé et de la Recherche Medicale (INSERM), Toulouse, France; Le Centre National de la Recherche Scientifique (CNRS), Toulouse, France; and Université de Toulouse III Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France.Department of Physiology and Pharmacology, Inflammation Research Network, University of Calgary, Calgary, Alberta, Canada; altier@ucalgary.ca.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26021808

Citation

Lapointe, Tamia K., et al. "TRPV1 Sensitization Mediates Postinflammatory Visceral Pain Following Acute Colitis." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 309, no. 2, 2015, pp. G87-99.
Lapointe TK, Basso L, Iftinca MC, et al. TRPV1 sensitization mediates postinflammatory visceral pain following acute colitis. Am J Physiol Gastrointest Liver Physiol. 2015;309(2):G87-99.
Lapointe, T. K., Basso, L., Iftinca, M. C., Flynn, R., Chapman, K., Dietrich, G., ... Altier, C. (2015). TRPV1 sensitization mediates postinflammatory visceral pain following acute colitis. American Journal of Physiology. Gastrointestinal and Liver Physiology, 309(2), pp. G87-99. doi:10.1152/ajpgi.00421.2014.
Lapointe TK, et al. TRPV1 Sensitization Mediates Postinflammatory Visceral Pain Following Acute Colitis. Am J Physiol Gastrointest Liver Physiol. 2015 Jul 15;309(2):G87-99. PubMed PMID: 26021808.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TRPV1 sensitization mediates postinflammatory visceral pain following acute colitis. AU - Lapointe,Tamia K, AU - Basso,Lilian, AU - Iftinca,Mircea C, AU - Flynn,Robyn, AU - Chapman,Kevin, AU - Dietrich,Gilles, AU - Vergnolle,Nathalie, AU - Altier,Christophe, Y1 - 2015/05/28/ PY - 2014/11/21/received PY - 2015/05/20/accepted PY - 2015/5/30/entrez PY - 2015/5/30/pubmed PY - 2015/9/29/medline KW - inflammatory bowel disease KW - peripheral sensitization KW - substance P KW - transient receptor potential vanilloid 1 KW - visceral pain SP - G87 EP - 99 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am. J. Physiol. Gastrointest. Liver Physiol. VL - 309 IS - 2 N2 - Quiescent phases of inflammatory bowel disease (IBD) are often accompanied by chronic abdominal pain. Although the transient receptor potential vanilloid 1 (TRPV1) ion channel has been postulated as an important mediator of visceral hypersensitivity, its functional role in postinflammatory pain remains elusive. This study aimed at establishing the role of TRPV1 in the peripheral sensitization underlying chronic visceral pain in the context of colitis. Wild-type and TRPV1-deficient mice were separated into three groups (control, acute colitis, and recovery), and experimental colitis was induced by oral administration of dextran sulfate sodium (DSS). Recovery mice showed increased chemically and mechanically evoked visceral hypersensitivity 5 wk post-DSS discontinuation, at which point inflammation had completely resolved. Significant changes in nonevoked pain-related behaviors could also be observed in these animals, indicative of persistent discomfort. These behavioral changes correlated with elevated colonic levels of substance P (SP) and TRPV1 in recovery mice, thus leading to the hypothesis that SP could sensitize TRPV1 function. In vitro experiments revealed that prolonged exposure to SP could indeed sensitize capsaicin-evoked currents in both cultured neurons and TRPV1-transfected human embryonic kidney (HEK) cells, a mechanism that involved TRPV1 ubiquitination and subsequent accumulation at the plasma membrane. Importantly, although TRPV1-deficient animals experienced similar disease severity and pain as wild-type mice in the acute phase of colitis, TRPV1 deletion prevented the development of postinflammatory visceral hypersensitivity and pain-associated behaviors. Collectively, our results suggest that chronic exposure of colon-innervating primary afferents to SP could sensitize TRPV1 and thus participate in the establishment of persistent abdominal pain following acute inflammation. SN - 1522-1547 UR - https://www.unboundmedicine.com/medline/citation/26021808/TRPV1_sensitization_mediates_postinflammatory_visceral_pain_following_acute_colitis_ L2 - http://www.physiology.org/doi/full/10.1152/ajpgi.00421.2014?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -