{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T11:20:22Z","timestamp":1788002422234,"version":"build-2784847793"},"posted":{"date-parts":[[2025,9,4]]},"group-title":"Bioengineering","reference-count":66,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["UG3-UH3 TR0003150"],"award-info":[{"award-number":["UG3-UH3 TR0003150"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Louisiana Board of Regents Departmental Enhancement","award":["LEQSF[2018-23]-ENH-DE-15"],"award-info":[{"award-number":["LEQSF[2018-23]-ENH-DE-15"]}]},{"name":"NSF Cell Manufacturing Technologies","award":["#1648035"],"award-info":[{"award-number":["#1648035"]}]},{"name":"NIH\/NINDS","award":["F32 NS106740"],"award-info":[{"award-number":["F32 NS106740"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Microphysiological systems (MPSs) are engineered, in vitro platforms which have been established as viable alternatives to animal models for pre-clinical research with unique advantages over conventional model systems. Many MPSs utilize 3-dimensional (3D) tissue constructs that enable biomimetic cell-cell interactions, allow for extended culture periods, and provide the time necessary for the emergence of physical and physiological characteristics of more mature tissues. Here, we present a novel MPS using human induced pluripotent stem cell (hiPSC)-derived spinal cord dorsal horn (SCDH) spheroids co-cultured with hiPSC-derived dorsal root ganglion (DRG) sensory spheroids in a microengineered hydrogel system to create a \u201cconnectoid\u201d model of afferent pain circuitry. SCDH spheroids were functionally innervated by peripheral sensory neurons, and prolonged maturation of hiPSC-derived SCDH neurons within the connectoid system enabled derivation of crucial late-born cell types unattainable using 2D differentiations. Furthermore, hiPSC-derived SCDH spheroids spontaneously generate rhythmic, complex, synaptically-driven electrophysiological waveforms that are disinhibited by morphine exposure, consistent with spinal mechanisms of opioid-induced pruritus and hypersensitivity.<\/jats:p>\n                <jats:sec>\n                  <jats:title>One Sentence Summary<\/jats:title>\n                  <jats:p>hiPSC-derived afferent sensory circuitry model, with NK1R+ spinal cord dorsal horn neurons, yields electrophysiologically mimetic response to opioids.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.08.31.673344","type":"posted-content","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T03:40:12Z","timestamp":1757043612000},"source":"Crossref","is-referenced-by-count":2,"title":["Human microphysiological model of dorsal root ganglion-spinal cord dorsal horn circuitry recapitulates opioid induced effects"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8503-0393","authenticated-orcid":false,"given":"Kevin J.","family":"Pollard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7823-5561","authenticated-orcid":false,"given":"Frank R.","family":"Seipel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9597-0936","authenticated-orcid":false,"given":"Nisha R.","family":"Iyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7531-8051","authenticated-orcid":false,"given":"Alex","family":"Bosak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6842-7022","authenticated-orcid":false,"given":"Randolph S.","family":"Ashton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7853-5756","authenticated-orcid":false,"given":"Michael J.","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025090818001634000_2025.08.31.673344v1.1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1080659"},{"key":"2025090818001634000_2025.08.31.673344v1.2","doi-asserted-by":"crossref","unstructured":"R. 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