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Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background: Acupuncture has been shown to promote gastrointestinal motility. This study explores whether cutaneous transient receptor potential vanilloid 1 (TRPV1)+ fibers at Zusanli (ST36) acupoint can mediate the multimodal effects of acupuncture on colorectal motility, as well as examining their mechanistic role. Methods: C57BL\/6 mice were subjected to electroacupuncture (EA), manual acupuncture (MA), 46 \u00b0C thermal stimulation, and 1% capsaicin at the ST36 acupoint. Colon motility was quantified via the area under the curve (AUC) and contraction amplitude. Immunofluorescent co-localization of TRPV1 with CGRP, NF200, peripherin, and tyrosine hydroxylase (TH) was conducted in TrpV1Cre mice to determine neural phenotypic subtypes. Furthermore, TrpV1ChR2-eYFP and TrpV1NpHR-eYFP transgenic mice that underwent optogenetic activation or silencing of local TRPV1+ fibers at ST36 were evaluated for acupuncture-like stimulation effects on colorectal AUC and amplitude. Results: All applied stimuli in C57BL\/6 mice significantly increased colorectal motility parameters (AUC and amplitude, p &lt; 0.05) compared to baseline. TRPV1+ somatosensory neurons in the dorsal root ganglion (DRG) predominantly co-expressed with peripherin (46.76%) and CGRP (27%), which are markers of unmyelinated peptidergic fibers, but rarely with NF200 (6%) or TH (&lt; 1%). Optogenetic activation (30 mW blue light) of TRPV1+ fibers in TrpV1ChR2-eYFP mice mimicked acupuncture-like stimuli, with significantly enhanced colorectal AUC and amplitude (p &lt; 0.05). In contrast, optogenetic silencing of TRPV1+ fibers with yellow light abolished acupuncture-like stimulation of colorectal motility in TrpV1NpHR-eYFP mice (p &lt; 0.05). Conclusion: Through the use of spatiotemporally precise optogenetic control, our study revealed that TRPV1+ sensory fibers at ST36 are the major convergent pathway for multimodal (electrical\/mechanical\/thermal\/chemical) enhancement of colorectal motility by acupuncture.<\/jats:p>","DOI":"10.31083\/fbl46975","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T12:05:26Z","timestamp":1769688326000},"source":"Crossref","is-referenced-by-count":1,"title":["Multimodal Enhancement of Colonic Motility by Acupuncture at ST36 is Mediated by TRPV1+ Cutaneous Sensory Fibers"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4416-8667","authenticated-orcid":true,"given":"Nan","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, 100700 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7043-7074","authenticated-orcid":true,"given":"Huilin","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, 100700 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6569-7510","authenticated-orcid":true,"given":"Xinyan","family":"Gao","sequence":"additional","affiliation":[{"name":"Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, 100700 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1653-0297","authenticated-orcid":true,"given":"Sha","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, 100700 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2787-7040","authenticated-orcid":true,"given":"Xia","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, 100700 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5727-9722","authenticated-orcid":true,"given":"Wang","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, 100700 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1388-3514","authenticated-orcid":true,"given":"Kun","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, 100700 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8766-5862","authenticated-orcid":true,"given":"Shuya","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, 100700 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0834-6068","authenticated-orcid":true,"given":"Bing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, 100700 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Liu Z, Yan S, Wu J, He L, Li N, Dong G, et al. 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