Academic Journal
Burst-patterned stimulation restores colonic motility in preclinical models.
| Τίτλος: | Burst-patterned stimulation restores colonic motility in preclinical models. |
|---|---|
| Συγγραφείς: | Barth BB; Department of Biomedical Engineering, Duke University, Durham, NC 27710, USA., Grill WM; Department of Biomedical Engineering, Duke University, Durham, NC 27710, USA.; Department of Electrical and Computer Engineering, Duke University, Durham, NC 27710, USA.; Department of Neurobiology, Duke University, Durham, NC 27710, USA.; Department of Neurosurgery, Duke University, Durham, NC 27710, USA. |
| Πηγή: | Science translational medicine [Sci Transl Med] 2025 Nov 05; Vol. 17 (823), pp. eadu4615. Date of Electronic Publication: 2025 Nov 05. |
| Τύπος έκδοσης: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101505086 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1946-6242 (Electronic) Linking ISSN: 19466234 NLM ISO Abbreviation: Sci Transl Med Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, DC : American Association for the Advancement of Science |
| Ιατρικοί όροι (MeSH): | Gastrointestinal Motility*/physiology , Colon*/physiopathology , Colon*/physiology , Electric Stimulation Therapy*/methods, Constipation/therapy ; Constipation/physiopathology ; Constipation/chemically induced ; Animals ; Rats ; Rats, Sprague-Dawley ; Disease Models, Animal ; Male ; Electric Stimulation ; Defecation ; Loperamide |
| Περίληψη: | Disrupted communication along the brain-gut axis contributes to impaired visceral function and debilitating symptoms. Colonic dysmotility, in particular, remains poorly managed by conventional pharmaceuticals. The objectives of our study were to restore colonic motility by electrical stimulation of the sacral nerves, optimize the stimulation pattern to relieve constipation, and elucidate the mechanisms of motor patterns evoked by stimulation. Through a combination of computational, ex vivo, and in vivo preclinical models, we engineered temporal patterns of sacral nerve stimulation to evoke maximally propulsive, prokinetic motility. We validated the optimized pattern of stimulation by measuring defecatory behavior in a loperamide model of constipation in rats. Compared with sham stimulation and the continuous pattern of stimulation conventionally used in the clinic, burst-patterned sacral nerve stimulation significantly increased fecal output to baseline and relieved constipation in awake, behaving rats. Further, we systematically varied stimulation frequency, stimulation duration, and interburst interval and determined the minimum effective parameters to maximize anorectal contractions. We demonstrated that a precise temporal pattern of sacral nerve stimulation relieves constipation in rats, establishing preclinical evidence and the foundational principles for translation to future pilot clinical trials. |
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| Grant Information: | R01 DK119795 United States DK NIDDK NIH HHS |
| Substance Nomenclature: | 6X9OC3H4II (Loperamide) |
| Entry Date(s): | Date Created: 20251105 Date Completed: 20251105 Latest Revision: 20261012 |
| Update Code: | 20261012 |
| PubMed Central ID: | PMC13653494 |
| DOI: | 10.1126/scitranslmed.adu4615 |
| PMID: | 41191773 |
| Βάση Δεδομένων: | MEDLINE |
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