{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:24:32Z","timestamp":1790166272658,"version":"4.1.0"},"reference-count":60,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T00:00:00Z","timestamp":1488326400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006393","name":"Universidad de Granada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006393","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000885","name":"Dr Hadwen Trust for Humane Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000885","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2017,4,15]]},"abstract":"<jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Voltage\u2010gated sodium channels play a fundamental role in determining neuronal excitability.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Specifically, voltage\u2010gated sodium channel subtype Na\n                            <jats:sub>V<\/jats:sub>\n                            1.7 is required for sensing acute and inflammatory somatic pain in mice and humans but its significance in pain originating from the viscera is unknown.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Using comparative behavioural models evoking somatic and visceral pain pathways, we identify the requirement for Na\n                            <jats:sub>V<\/jats:sub>\n                            1.7 in regulating somatic (noxious heat pain threshold) but not in visceral pain signalling.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>These results enable us to better understand the mechanisms underlying the transduction of noxious stimuli from the viscera, suggest that the investigation of pain pathways should be undertaken in a modality\u2010specific manner and help to direct drug discovery efforts towards novel visceral analgesics.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Voltage\u2010gated sodium channel Na\n                      <jats:sub>V<\/jats:sub>\n                      1.7 is required for acute and inflammatory pain in mice and humans but its significance for visceral pain is unknown. Here we examine the role of Na\n                      <jats:sub>V<\/jats:sub>\n                      1.7 in visceral pain processing and the development of referred hyperalgesia using a conditional nociceptor\u2010specific Na\n                      <jats:sub>V<\/jats:sub>\n                      1.7 knockout mouse (Na\n                      <jats:sub>V<\/jats:sub>\n                      1.7\n                      <jats:sup>Nav1.8<\/jats:sup>\n                      ) and selective small\u2010molecule Na\n                      <jats:sub>V<\/jats:sub>\n                      1.7 antagonist PF\u20105198007. Na\n                      <jats:sub>V<\/jats:sub>\n                      1.7\n                      <jats:sup>Nav1.8<\/jats:sup>\n                      mice showed normal nociceptive behaviours in response to intracolonic application of either capsaicin or mustard oil, stimuli known to evoke sustained nociceptor activity and sensitization following tissue damage, respectively. Normal responses following induction of cystitis by cyclophosphamide were also observed in both Na\n                      <jats:sub>V<\/jats:sub>\n                      1.7\n                      <jats:sup>Nav1.8<\/jats:sup>\n                      and littermate controls. Loss, or blockade, of Na\n                      <jats:sub>V<\/jats:sub>\n                      1.7 did not affect afferent responses to noxious mechanical and chemical stimuli in nerve\u2013gut preparations in mouse, or following antagonism of Na\n                      <jats:sub>V<\/jats:sub>\n                      1.7 in resected human appendix stimulated by noxious distending pressures. However, expression analysis of voltage\u2010gated sodium channel \u03b1 subunits revealed Na\n                      <jats:sub>V<\/jats:sub>\n                      1.7 mRNA transcripts in nearly all retrogradely labelled colonic neurons, suggesting redundancy in function. By contrast, using comparative somatic behavioural models we identify that genetic deletion of Na\n                      <jats:sub>V<\/jats:sub>\n                      1.7 (in Na\n                      <jats:sub>V<\/jats:sub>\n                      1.8\u2010expressing neurons) regulates noxious heat pain threshold and that this can be recapitulated by the selective Na\n                      <jats:sub>V<\/jats:sub>\n                      1.7 antagonist PF\u20105198007. Our data demonstrate that Na\n                      <jats:sub>V<\/jats:sub>\n                      1.7 (in Na\n                      <jats:sub>V<\/jats:sub>\n                      1.8\u2010expressing neurons) contributes to defined pain pathways in a modality\u2010dependent manner, modulating somatic noxious heat pain, but is not required for visceral pain processing, and advocate that pharmacological block of Na\n                      <jats:sub>V<\/jats:sub>\n                      1.7 alone in the viscera may be insufficient in targeting chronic visceral pain.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp272837","type":"journal-article","created":{"date-parts":[[2017,1,20]],"date-time":"2017-01-20T05:40:42Z","timestamp":1484890842000},"page":"2661-2679","source":"Crossref","is-referenced-by-count":74,"title":["Visceral and somatic pain modalities reveal Na\n                    <sub>V<\/sub>\n                    1.7\u2010independent visceral nociceptive pathways"],"prefix":"10.1113","volume":"595","author":[{"given":"James R. F.","family":"Hockley","sequence":"first","affiliation":[{"name":"Neuroscience and Pain Research Unit, Pfizer Ltd.  The Portway Building, Granta Science Park Cambridge CB21 6GS UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Gonz\u00e1lez\u2010Cano","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Biomedical Research Centre (CIBM) and Institute of Neuroscience, Faculty of Medicine University of Granada  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4469-6807","authenticated-orcid":false,"given":"Sheridan","family":"McMurray","sequence":"additional","affiliation":[{"name":"Neuroscience and Pain Research Unit, Pfizer Ltd.  The Portway Building, Granta Science Park Cambridge CB21 6GS UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A.","family":"Tejada\u2010Giraldez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Biomedical Research Centre (CIBM) and Institute of Neuroscience, Faculty of Medicine University of Granada  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cian","family":"McGuire","sequence":"additional","affiliation":[{"name":"National Centre for Bowel Research and Surgical Innovation, Blizard Institute, Barts and the London School of Medicine and Dentistry Queen Mary University of London  London E1 2AT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Torres","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Biomedical Research Centre (CIBM) and Institute of Neuroscience, Faculty of Medicine University of Granada  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna L.","family":"Wilbrey","sequence":"additional","affiliation":[{"name":"Neuroscience and Pain Research Unit, Pfizer Ltd.  The Portway Building, Granta Science Park Cambridge CB21 6GS UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8483-0284","authenticated-orcid":false,"given":"Vincent","family":"Cibert\u2010Goton","sequence":"additional","affiliation":[{"name":"National Centre for Bowel Research and Surgical Innovation, Blizard Institute, Barts and the London School of Medicine and Dentistry Queen Mary University of London  London E1 2AT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco R.","family":"Nieto","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Biomedical Research Centre (CIBM) and Institute of Neuroscience, Faculty of Medicine University of Granada  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Pitcher","sequence":"additional","affiliation":[{"name":"Neuroscience and Pain Research Unit, Pfizer Ltd.  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