{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:47:35Z","timestamp":1789577255890,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","award":["G113502"],"award-info":[{"award-number":["G113502"]}],"id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Managing visceral pain associated with gastrointestinal (GI) disease remains a significant challenge due to the gut\u2010related side effects and contraindicated use of many commonly used painkillers in people with inflammatory bowel disease (IBD). Consequently, it is crucial to deepen our understanding of the mediators and mechanisms underlying inflammatory pain in people with IBD. To do this, we compared bulk RNA sequencing data from colonic biopsy samples from people with IBD with single\u2010cell RNA sequencing data from colon\u2010projecting dorsal root ganglion (DRG) neurons in mice to generate an interactome of putative pro\u2010nociceptive cytokine signalling pathways. This in silico analysis revealed a 10\u2010fold increase in\n                    <jats:italic>IL17A<\/jats:italic>\n                    expression in samples from people with ulcerative colitis (UC) alongside marked co\u2010expression of\n                    <jats:italic>Il17ra<\/jats:italic>\n                    with\n                    <jats:italic>Trpv1<\/jats:italic>\n                    in colon\u2010projecting DRG neurons in mice, highlighting a likely role for interleukin\u201017 (IL\u201017) in colonic nociceptor signalling in people with UC. In support of this, Ca\n                    <jats:sup>2+<\/jats:sup>\n                    imaging studies demonstrated that IL\u201017 stimulates DRG sensory neurons co\u2010sensitive to capsaicin in male and female mice, with a similar proportion responding in neuron\u2010enriched cultures generated by magnetic\u2010activated cell sorting, thus confirming that IL\u201017 directly activates DRG neurons. IL\u201017\u2010evoked Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signals were attenuated by TRPV1 inhibition, consistent with nociceptor activation, and blocked by inhibition of phosphoinositide 3\u2010kinase (PI3K) activity, consistent with the known role for PI3K as a downstream effector of IL\u201017 receptor signalling. In keeping with these observations, IL\u201017 enhanced colonic afferent responses to colorectal distension at noxious distension pressures in male mice, an effect also blocked by PI3K inhibition. Overall, these findings demonstrate a pro\u2010nociceptive effect of IL\u201017 in the GI tract, thus highlighting the potential utility of IL\u201017\u2010targeting therapies to reduce pain in people with UC.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70191-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70191","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T09:27:59Z","timestamp":1755595679000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<scp>IL<\/scp>\n                    \u201017 Stimulates Sensory Neurons and Sensitises Colonic Afferents to Noxious Stimuli in a\n                    <scp>PI3K<\/scp>\n                    Dependent Manner in Male Mice"],"prefix":"10.1111","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4099-4648","authenticated-orcid":false,"given":"Luke W.","family":"Paine","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P.","family":"Higham","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Cambridge  Cambridge 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