OSCR

Temporal multi-omic exploration of the ventral tegmental area in chronic pain and passive coping behaviors.

Overview

Authors: Cody C Diezel1,2, Lisa A Majuta1,2, Erfan Bahramnejad1,2, Kelly L Karlage1,2, Jennifer L Partin1,2, Saniya MD Barbour3, Ingrid L Peterson1,2, Matthew Flowers1,2, Sophia T von Hippel1,2, Riley Haveman1,2, Ethan Villarroel1,2, Isabella Villarroel1,2, Paul R Langlais3, Tally M Largent-Milnes1,2, Todd W Vanderah1,2, Arthur C Riegel1,2,4,5
ORCID iDs: Cody C Diezel, Arthur C Riegel
  1. Comprehensive Center for Pain and Addiction (CCPA), University of Arizona, Tucson, AZ 85724, USA
  2. Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA
  3. Department of Medicine, Division of Endocrinology, University of Arizona, Tucson, AZ 85724, USA
  4. Department of Neuroscience, College of Science, University of Arizona, Tucson, AZ 85724, USA
  5. James C. Wyant College of Optical Sciences, University of Arizona, Tucson, AZ 85724, USA
Institutions: University of Arizona (United States)
Journal: iScience, volume 29, issue 6, article 116085
Dates: received 24 November 2025; accepted 13 April 2026; published online 22 May 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1016/j.isci.2026.116085 · PMID 42231966 · PMCID PMC13224009 · OpenAlex W7162107297
Open access: gold, a free copy (OpenAlex)
Status: code on request
Categories: genetics / omics (modality), pain (population), cellular / molecular (subfield)
Methods: Statistics, Smoothing, state filtering, decompositions, Machine learning, Preprocessing, fMRI & imaging
Keywords: molecular neuroscience, cell, proteomics
Topic: Pain Mechanisms and Treatments (Physiology, Medicine), according to OpenAlex
Funding: University of Arizona; NIDA NIH HHS (P30 DA051355); National Institute on Drug Abuse (P30DA051355); National Institutes of Health
Citations: not cited yet (Europe PMC); 99 references in the paper
Research resources: Rabbit Monoclonal Anti-CaMKI RRID:AB_1140889, Rabbit Polyclonal Anti-KCNQ2 RRID:AB_2040101, Rabbit Polyclonal Anti-KCNQ3 RRID:AB_2040103, RRID:AB_2340460, RRID:AB_2340619, Rabbit Polyclonal Anti-KCNQ5 RRID:AB_2341038, Rabbit Polyclonal Anti-KCNQ4 RRID:AB_2341042, RRID:AB_2619897, Mouse: C57BL/6J RRID:IMSR_JAX:000664

Abstract

The comorbidity of chronic pain and mood disorders poses a clinical challenge involving neurobiological mechanisms within key brain regions like the ventral tegmental area (VTA). We employed a multidisciplinary approach in male mice, combining proteomics, phosphoproteomics, and lipidomics with behavioral and immunohistochemical analyses in a neuropathic pain model. Our findings reveal a temporal evolution of the VTA molecular landscape—an early signature related to metabolic reallocation followed by a late maladaptive state characterized by shifts in energy metabolism and cytoskeletal remodeling. This late maladaptive state involved stoichiometric remodeling of Kv7 potassium channel subunits and depletion of the endocannabinoid 2-arachidonoylglycerol (2-AG), coinciding with the passive coping behavior. Pharmacological administration of 2-AG or potentiation of Kv7 channel function reversed pain-induced passive coping. Together, these findings delineate a temporal molecular evolution in the VTA and validate 2-AG and Kv7 systems as regulatory nodes linking chronic pain to the emergence of passive coping behaviors.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none (its code is available on request), so it has no map.

Data

Datasets cited

Data and code availability

Data: Mass spectrometry proteomics and phosphoproteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE74 partner repository and are publicly available under the dataset identifier ProteomeXchange: PXD072701 and https://doi.org/10.6019/PXD072701. Original data have been deposited to Mendeley Data and are publicly available at Mendeley Data: https://doi.org/10.17632/smp9jdthxy.1.75

Code: This paper does not report original code.

Other items: Any additional information necessary for reanalysis is available from the lead contact upon request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 16 authors, 3 keywords, 4 funders, 97 references, 9 RRIDs.

Cite

This paper

Diezel, C. C., Majuta, L. A., Bahramnejad, E., Karlage, K. L., Partin, J. L., Barbour, S. M., Peterson, I. L., Flowers, M., von Hippel, S. T., Haveman, R., Villarroel, E., Villarroel, I., Langlais, P. R., Largent-Milnes, T. M., Vanderah, T. W., & Riegel, A. C. (2026). Temporal multi-omic exploration of the ventral tegmental area in chronic pain and passive coping behaviors. iScience, 29(6), 116085. https://doi.org/10.1016/j.isci.2026.116085

BibTeX

@article{diezel2026temporal,
author = {Diezel, Cody C and Majuta, Lisa A and Bahramnejad, Erfan and Karlage, Kelly L and Partin, Jennifer L and Barbour, Saniya MD and Peterson, Ingrid L and Flowers, Matthew and von Hippel, Sophia T and Haveman, Riley and Villarroel, Ethan and Villarroel, Isabella and Langlais, Paul R and Largent-Milnes, Tally M and Vanderah, Todd W and Riegel, Arthur C},
title = {{Temporal multi-omic exploration of the ventral tegmental area in chronic pain and passive coping behaviors}},
journal = {iScience},
year = {2026},
month = may,
volume = {29},
number = {6},
pages = {116085},
publisher = {Elsevier},
issn = {2589-0042},
doi = {10.1016/j.isci.2026.116085},
url = {https://doi.org/10.1016/j.isci.2026.116085},
pmid = {42231966},
pmcid = {PMC13224009}
}

RIS

TY - JOUR
AU - Diezel, Cody C
AU - Majuta, Lisa A
AU - Bahramnejad, Erfan
AU - Karlage, Kelly L
AU - Partin, Jennifer L
AU - Barbour, Saniya MD
AU - Peterson, Ingrid L
AU - Flowers, Matthew
AU - von Hippel, Sophia T
AU - Haveman, Riley
AU - Villarroel, Ethan
AU - Villarroel, Isabella
AU - Langlais, Paul R
AU - Largent-Milnes, Tally M
AU - Vanderah, Todd W
AU - Riegel, Arthur C
TI - Temporal multi-omic exploration of the ventral tegmental area in chronic pain and passive coping behaviors
T2 - iScience
J2 - iScience
PY - 2026
DA - 2026/05/22
VL - 29
IS - 6
SP - 116085
SN - 2589-0042
PB - Elsevier
DO - 10.1016/j.isci.2026.116085
UR - https://doi.org/10.1016/j.isci.2026.116085
LA - en
ER -

CSL-JSON

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