Evidence map›Paper›PMID 36330161›Full record

ArticleBioactive materials2023

Engineering human spinal microphysiological systems to model opioid-induced tolerance.

Hongwei Cai, Zheng Ao, Chunhui Tian, Zhuhao Wu, Connor Kaurich, Zi Chen, Mingxia Gu, Andrea G Hohmann, Ken Mackie, Feng Guo

Open access · goldAbstract read
In one paragraph

Article in Bioactive materials, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
3.8field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Article
  3. Organoid Brain-Machine-Interface Devices for Central Nervous System Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  4. Review
  5. Review
  6. Decoding Pain: Next-Generation In Vitro Systems for Mechanistic Insights and Drug Discovery.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Human brain organoids for understanding substance use disorders.Drug metabolism and pharmacokinetics · 2025
    Review
  13. Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024
    Review
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Hongwei CaiDepartment of Intelligent Systems Engineering, Indiana University, Bloomington, IN, 47405, United States.
Zheng AoDepartment of Intelligent Systems Engineering, Indiana University, Bloomington, IN, 47405, United States.
Chunhui TianDepartment of Intelligent Systems Engineering, Indiana University, Bloomington, IN, 47405, United States.
Zhuhao WuDepartment of Intelligent Systems Engineering, Indiana University, Bloomington, IN, 47405, United States.
Connor KaurichDepartment of Intelligent Systems Engineering, Indiana University, Bloomington, IN, 47405, United States.
Zi ChenDepartment of Surgery, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, 02115, United States.
Mingxia GuDivision of Pulmonary Biology, Center for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, United States.
Andrea G HohmannGill Center for Biomolecular Science, and Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, 47405, United States.
Ken MackieGill Center for Biomolecular Science, and Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, 47405, United States.
Feng GuoDepartment of Intelligent Systems Engineering, Indiana University, Bloomington, IN, 47405, United States.
Indiana University Bloomington · USBrigham and Women's Hospital · USCincinnati Children's Hospital Medical Center · US

Funding

An automated portable system for detecting and treating opioid induced respiratory depressionU01DA056242 · NIDA · TRUSTEES OF INDIANA UNIVERSITY · PI GUO, FENG, MACKIE, KENNETH · 2022 to 2024
$3.8M
Early detection of type 1 diabetes via Exosome Technology with Optoelectronics Lab-on-chip: EXTOLR01DK133864 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI GAGLIA, JASON, GUO, FENG · 2022 to 2025
$3.0M
CB2 Cannabinoid Mechanisms for Suppressing Opioid Tolerance and DependenceR01DA047858 · NIDA · TRUSTEES OF INDIANA UNIVERSITY · PI HOHMANN, ANDREA GRACE, MACKIE, KENNETH · 2019 to 2023
$2.6M
An acoustofluidic avidity cytometer for massive parallel profiling single autoreactive T cell in autoimmune diseaseDP2AI160242 · NIAID · TRUSTEES OF INDIANA UNIVERSITY · PI GUO, FENG · 2020 to 2020
$2.4M
NIAID NIH HHS DP2 AI160242NIDA NIH HHS R01 DA047858NIDA NIH HHS U01 DA056242NIDDK NIH HHS R01 DK133864
6 · The paper itself

Abstract

pioids are commonly used for treating chronic pain. However, with continued use, they may induce tolerance and/or hyperalgesia, which limits therapeutic efficacy. The human mechanisms of opioid-induced tolerance and hyperalgesia are significantly understudied, in part, because current models cannot fully recapitulate human pathology. Here, we engineered novel human spinal microphysiological systems (MPSs) integrated with plug-and-play neural activity sensing for modeling human nociception and opioid-induced tolerance. Each spinal MPS consists of a flattened human spinal cord organoid derived from human stem cells and a 3D printed organoid holder device for plug-and-play neural activity measurement. We found that the flattened organoid design of MPSs not only reduces hypoxia and necrosis in the organoids, but also promotes their neuron maturation, neural activity, and functional development. We further demonstrated that prolonged opioid exposure resulted in neurochemical correlates of opioid tolerance and hyperalgesia, as measured by altered neural activity, and downregulation of μ-opioid receptor expression of human spinal MPSs. The MPSs are scalable, cost-effective, easy-to-use, and compatible with commonly-used well-plates, thus allowing plug-and-play measurements of neural activity. We believe the MPSs hold a promising translational potential for studying human pain etiology, screening new treatments, and validating novel therapeutics for human pain medicine.

Indexed as

In-situ electrical sensingMicrophysiological systemsNeural activityOpioid-induced tolerance and hyperalgesiaOrgan-on-chipSpinal cord organoids

Identifiers

PMID36330161
PMCPMC9618681
OpenAlexW4307224194

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.