{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:24:55Z","timestamp":1789950295709,"version":"4.0.1"},"reference-count":81,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mol Pain"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Chronic visceral pain is a defining symptom of many gastrointestinal disorders. The K\n                      <jats:sub>V<\/jats:sub>\n                      7 family (K\n                      <jats:sub>V<\/jats:sub>\n                      7.1\u2013K\n                      <jats:sub>V<\/jats:sub>\n                      7.5) of voltage-gated potassium channels mediates the M current that regulates excitability in peripheral sensory nociceptors and central pain pathways. Here, we use a combination of immunohistochemistry, gut-nerve electrophysiological recordings in both mouse and human tissues, and single-cell qualitative real-time polymerase chain reaction of gut-projecting sensory neurons, to investigate the contribution of peripheral K\n                      <jats:sub>V<\/jats:sub>\n                      7 channels to visceral nociception.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Immunohistochemical staining of mouse colon revealed labelling of K\n                      <jats:sub>V<\/jats:sub>\n                      7 subtypes (K\n                      <jats:sub>V<\/jats:sub>\n                      7.3 and K\n                      <jats:sub>V<\/jats:sub>\n                      7.5) with CGRP around intrinsic enteric neurons of the myenteric plexuses and within extrinsic sensory fibres along mesenteric blood vessels. Treatment with the K\n                      <jats:sub>V<\/jats:sub>\n                      7 opener retigabine almost completely abolished visceral afferent firing evoked by the algogen bradykinin, in agreement with significant co-expression of mRNA transcripts by single-cell qualitative real-time polymerase chain reaction for KCNQ subtypes and the B\n                      <jats:sub>2<\/jats:sub>\n                      bradykinin receptor in retrogradely labelled extrinsic sensory neurons from the colon. Retigabine also attenuated responses to mechanical stimulation of the bowel following noxious distension (0\u201380\u2009mmHg) in a concentration-dependent manner, whereas the K\n                      <jats:sub>V<\/jats:sub>\n                      7 blocker XE991 potentiated such responses. In human bowel tissues, K\n                      <jats:sub>V<\/jats:sub>\n                      7.3 and K\n                      <jats:sub>V<\/jats:sub>\n                      7.5 were expressed in neuronal varicosities co-labelled with synaptophysin and CGRP, and retigabine inhibited bradykinin-induced afferent activation in afferent recordings from human colon.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We show that K\n                      <jats:sub>V<\/jats:sub>\n                      7 channels contribute to the sensitivity of visceral sensory neurons to noxious chemical and mechanical stimuli in both mouse and human gut tissues. As such, peripherally restricted K\n                      <jats:sub>V<\/jats:sub>\n                      7 openers may represent a viable therapeutic modality for the treatment of gastrointestinal pathologies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1744806917709371","type":"journal-article","created":{"date-parts":[[2017,6,1]],"date-time":"2017-06-01T02:10:36Z","timestamp":1496283036000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":47,"title":["Peripheral K\n                    <sub>V<\/sub>\n                    7 channels regulate visceral sensory function in mouse and human colon"],"prefix":"10.1177","volume":"13","author":[{"given":"Madusha","family":"Peiris","sequence":"first","affiliation":[{"name":"Centre for Neuroscience and Trauma, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James RF","family":"Hockley","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E","family":"Reed","sequence":"additional","affiliation":[{"name":"GI Diseases Research Unit, Queen\u2019s University, Kingston, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewan St. John","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C","family":"Bulmer","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience and Trauma, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L Ashley","family":"Blackshaw","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience and Trauma, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2017,5,31]]},"reference":[{"key":"bibr1-1744806917709371","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2008.12.011"},{"key":"bibr2-1744806917709371","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2006.05.015"},{"key":"bibr3-1744806917709371","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-18-07227.2003"},{"key":"bibr4-1744806917709371","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00111.x"},{"key":"bibr5-1744806917709371","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2014.08.025"},{"key":"bibr6-1744806917709371","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-15-05535.2001"},{"key":"bibr7-1744806917709371","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1575-05.2006"},{"key":"bibr8-1744806917709371","doi-asserted-by":"publisher","DOI":"10.1007\/s40268-016-0148-6"},{"key":"bibr9-1744806917709371","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-10-15"},{"key":"bibr10-1744806917709371","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2012.12.005"},{"key":"bibr11-1744806917709371","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.06.048"},{"key":"bibr12-1744806917709371","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2012.00063"},{"key":"bibr13-1744806917709371","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1473-13.2013"},{"key":"bibr14-1744806917709371","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.32387"},{"key":"bibr15-1744806917709371","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.126599"},{"key":"bibr16-1744806917709371","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2297-08.2008"},{"key":"bibr17-1744806917709371","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-011-0862-7"},{"key":"bibr18-1744806917709371","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4932-06.2007"},{"key":"bibr19-1744806917709371","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2006.11.043"},{"key":"bibr20-1744806917709371","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2010.12.028"},{"key":"bibr21-1744806917709371","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-7-84"},{"key":"bibr22-1744806917709371","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.192823"},{"key":"bibr23-1744806917709371","doi-asserted-by":"publisher","DOI":"10.1007\/s004240100609"},{"key":"bibr24-1744806917709371","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00057.2009"},{"key":"bibr25-1744806917709371","doi-asserted-by":"publisher","DOI":"10.1038\/35036198"},{"key":"bibr26-1744806917709371","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2008.04.006"},{"key":"bibr27-1744806917709371","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.113308"},{"key":"bibr28-1744806917709371","author":"McGuire 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