{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T23:50:43Z","timestamp":1780617043912,"version":"3.54.1"},"reference-count":95,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"823","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,11,5]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1126\/scitranslmed.adu4615","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T18:58:26Z","timestamp":1762369106000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":3,"title":["Burst-patterned stimulation restores colonic motility in preclinical models"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4344-7182","authenticated-orcid":true,"given":"Bradley B.","family":"Barth","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Duke University, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5240-6588","authenticated-orcid":true,"given":"Warren M.","family":"Grill","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Duke University, Durham, NC 27710, USA."},{"name":"Department of Electrical and Computer Engineering, Duke University, Durham, NC 27710, USA."},{"name":"Department of Neurobiology, Duke University, Durham, NC 27710, USA."},{"name":"Department of Neurosurgery, Duke University, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1895.sp000558"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-018-0078-6"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1980.sp013073"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.surge.2014.11.002"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.8760"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1973.tb05499.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2015.101"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00463.2020"},{"key":"e_1_3_2_10_2","unstructured":"B. B. Barth N. J. Spencer W. M. Grill in The Enteric Nervous System II N. J. Spencer M. Costa S. M. Brierley Eds. (Springer International Publishing 2022) pp. 113\u2013123."},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.14815"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnbot.2022.983072"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cobme.2024.100557"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1088\/1741-2552\/aa86c8"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2018.02.038"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.67858"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.199034"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.08.003"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0039887"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.047944"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.FP0050973"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00510.2007"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00436.2012"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.018705"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13089"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00449.2013"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.14098"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00109"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.256230"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.05.016"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(91)90723-X"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.04.034"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.06.034"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1113\/JP273269"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1049\/htl.2018.5030"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1088\/1741-2552\/ac36e2"},{"key":"e_1_3_2_37_2","first-page":"121","article-title":"Response of single alpha motoneurons to high-frequency pulse trains. Firing behavior and conduction block phenomenon","volume":"49","author":"Bowman B. R.","year":"1986","unstructured":"B. R. Bowman, D. R. McNeal, Response of single alpha motoneurons to high-frequency pulse trains. Firing behavior and conduction block phenomenon. Appl. Neurophysiol. 49, 121\u2013138 (1986).","journal-title":"Appl. Neurophysiol."},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2023.10.021"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00238.2012"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2022.08.034"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00100.2025"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.3390\/mi9090428"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1111\/ner.13092"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12546"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0167-1"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.5056\/jnm15181"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00319.2011"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.309bz.x"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.2001.281.1.G255"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1177\/1744806919880651"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13825"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1111\/ner.13255"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1111\/ner.13117"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1097\/SPV.0000000000000188"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1097\/SPV.0000000000000457"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1002\/nau.22962"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1002\/nau.22938"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10151-013-0999-6"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00116.2017"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1002\/ar.a.10116"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(89)90433-2"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2003.08.004"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.3389\/neuro.11.001.2009"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.44494"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.24872"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-7580.1997.19020209.x"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.083600"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12302"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.219519"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.259796"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12195-017-0479-6"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018685"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-1838(97)00092-1"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1991.260.1.G80"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1988.sp017409"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.2174\/157015907780077141"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(86)90601-1"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1038\/274387a0"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(85)90590-4"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1987.sp016860"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.01407"},{"key":"e_1_3_2_82_2","unstructured":"H. P. Rang M. M. Dale P. Lamb J. M. Ritter P. Moore Pharmacology (Churchill Livingstone 2003)."},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1212656110"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2012.tb00453.x"},{"key":"e_1_3_2_85_2","unstructured":"C. W. Cleghorn A. P. Engelbrecht in Swarm Intelligence M. Dorigo M. Birattari S. Garnier H. Hamann M. Montes de Oca C. Solnon T. St\u00fctzle Eds. (Springer International Publishing 2014) pp. 134\u2013145."},{"key":"e_1_3_2_86_2","unstructured":"Y. Shi R. Eberhart in 1998 IEEE International Conference on Evolutionary Computation Proceedings. IEEE World Congress on Computational Intelligence (Cat. No.98TH8360) (IEEE 1998) pp. 69\u201373."},{"key":"e_1_3_2_87_2","unstructured":"P. K. Lehre C. Witt in Advances in Metaheuristics L. Di Gaspero A. Schaerf T. St\u00fctzle Eds. (Springer 2013) pp. 1\u201320."},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2008.03884.x"},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2008.162404"},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0800670"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1983.sp014791"},{"key":"e_1_3_2_92_2","unstructured":"J. E. Bornstein P. Zarei Small enteric neural network simulator version 7 Pennsieve Discover (2019); https:\/\/doi.org\/10.26275\/I3XV-FOFG."},{"key":"e_1_3_2_93_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00228.2013"},{"key":"e_1_3_2_94_2","first-page":"1","article-title":"Enteric glia","volume":"1","author":"Gulbransen B. D.","year":"2014","unstructured":"B. D. Gulbransen, Enteric glia. CSNBM 1, 1\u201370 (2014).","journal-title":"CSNBM"},{"key":"e_1_3_2_95_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmbbm.2017.08.031"},{"key":"e_1_3_2_96_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1976.sp011628"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.adu4615","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T18:58:28Z","timestamp":1762369108000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.adu4615"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,5]]},"references-count":95,"journal-issue":{"issue":"823","published-print":{"date-parts":[[2025,11,5]]}},"alternative-id":["10.1126\/scitranslmed.adu4615"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.adu4615","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,5]]},"assertion":[{"value":"2024-11-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-08","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadu4615"}}