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However, the peripheral neurophysiological mechanisms of visceral referred pain remain unclear. This study aimed to clarify the neurobiological mechanisms that underpin the referred somatic hyperalgesia associated with UC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A UC mouse model was constructed via the administration of dextran sulfate sodium (DSS). Referred somatic regions in these mice were identified by measuring the number of Evans blue extravasations and pain threshold levels. Electrophysiological and immunofluorescent staining approaches were applied to evaluate the alterations in kinetic properties and expression of TTX\u2010R (Na\n                      <jats:sub>v<\/jats:sub>\n                      1.8) and TTX\u2010S (Na\n                      <jats:sub>v<\/jats:sub>\n                      1.7) channels in calcitonin gene\u2010related peptide (CGRP)\u2010positive dorsal root ganglion (DRG) neurons in the referred regions. Pharmacological methods were utilized to elucidate the necessary role of the Na\n                      <jats:sub>v<\/jats:sub>\n                      1.8 and Na\n                      <jats:sub>v<\/jats:sub>\n                      1.7 channels in somatic referred hyperalgesia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Oral administration of DSS to mice for 7\u2009days resulted in significant colon damage, neurogenic inflammation, and referred somatic hyperalgesia. The mechanisms underlying these effects may involve the activation of TTX\u2010R and TTX\u2010S channels, and the upregulation of co\u2010expressed Na\n                      <jats:sub>v<\/jats:sub>\n                      1.8 and Na\n                      <jats:sub>v<\/jats:sub>\n                      1.7 with CGRP, resulting in an increased excitability of CGRP\n                      <jats:sup>+<\/jats:sup>\n                      DRG neurons in sensitized regions. Selectively inhibiting either Na\n                      <jats:sub>v<\/jats:sub>\n                      1.8 or Na\n                      <jats:sub>v<\/jats:sub>\n                      1.7 channels could mitigate the referred somatic hyperalgesia induced by DSS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Inferences<\/jats:title>\n                    <jats:p>\n                      The functional alterations in Na\n                      <jats:sub>v<\/jats:sub>\n                      1.8 and Na\n                      <jats:sub>v<\/jats:sub>\n                      1.7 channels within CGRP\n                      <jats:sup>+<\/jats:sup>\n                      DRG neurons are pivotal to the development of neurogenic inflammation and referred somatic hyperalgesia. These findings lay a foundation for exploring novel therapeutic targets to relieve visceral referred pain.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nmo.70051","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T15:09:33Z","timestamp":1745507373000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>TTX<\/scp>\n                    \u2010R and\n                    <scp>TTX<\/scp>\n                    \u2010S Sodium Channels in\n                    <scp>CGRP<\/scp>\n                    \u2010Positive Dorsal Root Ganglia Neurons Mediate Referred Somatic Hyperalgesia in Ulcerative Colitis Mice"],"prefix":"10.1111","volume":"37","author":[{"given":"Yongbin","family":"Liu","sequence":"first","affiliation":[{"name":"Shaanxi Key Laboratory of Integrative Acupuncture and Medicine Shaanxi University of Chinese Medicine  Xianyang Shaanxi Province 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Integrative Acupuncture and Medicine Shaanxi University of Chinese Medicine  Xianyang Shaanxi Province China"},{"name":"Key Laboratory of Acupuncture and Neurobiology Shaanxi Administration of Traditional Chinese Medicine  Xianyang Shaanxi Province China"},{"name":"College of Acupuncture\u2010Moxibustion and Tuina Shaanxi University of Chinese Medicine  Xianyang Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanhuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Integrative Acupuncture and Medicine Shaanxi University of Chinese Medicine  Xianyang Shaanxi Province China"},{"name":"Key Laboratory of Acupuncture and Neurobiology Shaanxi Administration of Traditional Chinese Medicine  Xianyang Shaanxi Province China"},{"name":"College of Acupuncture\u2010Moxibustion and Tuina Shaanxi University of Chinese Medicine  Xianyang Shaanxi Province 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