Evidence map›Paper›PMID 41384944›Full record

ArticlePain2026

Hemorphins, atypical endogenous opiate peptides, in sickle cell disease and their association with pain.

Yanqi Tan, Yavnika Kashyap, Eduardo De La Toba, Seth W Croslow, Meghna Gill, Xiao Guo, Giokdjen Ilktach, Erin Davy, Robert Molokie, Zaijie Jim Wang and 1 more

Abstract read
In one paragraph

Article in Pain, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Article
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

11 authors.

Yanqi TanDepartment of Chemistry and the Beckman Institute, University of Illinois Urbana-Champaign, Urbana, IL, United States.
Yavnika KashyapDepartment of Pharmaceutical Sciences, University of Illinois Chicago, Chicago, IL, United States.
Eduardo De La TobaDepartment of Chemistry and the Beckman Institute, University of Illinois Urbana-Champaign, Urbana, IL, United States.
Seth W CroslowDepartment of Chemistry and the Beckman Institute, University of Illinois Urbana-Champaign, Urbana, IL, United States.
Meghna GillDepartment of Pharmaceutical Sciences, University of Illinois Chicago, Chicago, IL, United States.
Xiao GuoDepartment of Pharmaceutical Sciences, University of Illinois Chicago, Chicago, IL, United States.
Giokdjen IlktachDepartment of Pharmaceutical Sciences, University of Illinois Chicago, Chicago, IL, United States.
Erin DavySchool of Molecular and Cellular Biology, University of Illinois Urbana-Champaign, Urbana, IL, United States.
Robert MolokieDepartment of Pharmaceutical Sciences, University of Illinois Chicago, Chicago, IL, United States.
Zaijie Jim WangDepartment of Pharmaceutical Sciences, University of Illinois Chicago, Chicago, IL, United States.
Jonathan V SweedlerDepartment of Chemistry and the Beckman Institute, University of Illinois Urbana-Champaign, Urbana, IL, United States.ORCID 0000-0003-3107-9922

Funding

The UIUC Neuroproteomics Center on Cell-Cell SignalingP30DA018310 · NIDA · UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN · PI Jonathan V. Sweedler · 2004 to 2026
$24.9M
Molecular mechanism and targeting of chronic pain in sickle cell diseaseR35HL140031 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI WANG, ZAIJIE JIM · 2018 to 2024
$4.6M
Molecular Mechanism and Targeting of Chronic Pain in Sickle Cell DiseaseR35HL177406 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI Zaijie Jim Wang · 2025 to 2026
$2.2M
NHLBI NIH HHS R35 HL140031NHLBI NIH HHS R35HL140031NHLBI NIH HHS R35 HL177406NHLBI NIH HHS R35HL177406NIDA NIH HHS P30 DA018310NIDA NIH HHS P30DA018310
6 · The paper itself

Abstract

abstractSickle cell disease (SCD) is a genetic disorder caused by a mutation in the beta hemoglobin gene, resulting in red blood cell (RBC) distortion, hemolysis, and severe pain episodes. Despite advancements in understanding acute crisis pain that is caused by vaso-occlusion, the neurobiological mechanisms underlying chronic pain in SCD remain poorly studied. Hemorphins, atypical endogenous opioid peptides derived from the hemoglobin beta chain in RBCs have analgesic effects and may contribute to SCD-related pain mechanisms, as their formation occurs when hemoglobin in RBCs is exposed to proteases in plasma. In this study, we investigated the levels of hemorphins in both plasma and nervous system of humanized transgenic SCD mice using liquid chromatography mass spectrometry. Our results show a significant elevation of hemorphins in SCD mice compared with wild-type controls, with a strong correlation with individual pain levels. These findings suggest that altered hemorphin processing in SCD may contribute to chronic pain by modulating the opioid signaling pathways, offering insights into the neurobiology of pain in SCD.

Indexed as

Anemia, Sickle CellHemoglobinsOpioid PeptidesPainAnimalsDisease Models, AnimalFemaleHumansMaleMiceMice, TransgenicHemoglobinsOpioid PeptidesCathepsin DEndogenous opioid peptideHemoglobinHemorphinsPeptide hormoneSickle cell disease

Identifiers

PMID41384944
PMCPMC12959964

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Registered trials

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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.