Effective combinational treatment of chronic pain in individual patients, by an innovative quantitative systems pharmacology pain relief approach.

Project Information

QSPainRelief

Grant agreement ID: 848068

DOI

10.3030/848068

Project closed

EC signature date 13 December 2019

Start date 1 January 2020

End date 30 June 2025

Funded under

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Total cost

€ 6 239 539,25

EU contribution

€ 6 239 538,75

Coordinated by

UNIVERSITEIT LEIDEN
Netherlands

CORDIS provides links to public deliverables and publications of HORIZON projects.

Links to deliverables and publications from FP7 projects, as well as links to some specific result types such as dataset and software, are dynamically retrieved from OpenAIRE .

Deliverables

Other (2)

2nd patient and layman event

Jointly with one of the relevant patient organisations, the second layman event will take place before the end of the second year, including a Q & A session at a convenient location (most likely connected to a GA Meeting) where partnering clinicians and researchers explain the scope of the project, present most recent results, and answer questions of patients and the general public.

1st patient and layman event

Jointly with one of the relevant patient organisations, the first layman event will take place within the first 6 months, including a Q & A session at a convenient location (most likely connected to an SC Meeting) where partnering clinicians and researchers explain the scope of the project and answer questions of patients and the general public.

Websites, patent fillings, videos etc. (3)

Go-online of the public project website

The public project website will serve several purposes, including a) being the central go-to-point for consortium members to look up contact information of other partners and to log into the confidential intranet, b) providing a concise overview of the project’s goals, its work packages, and the scientific background to the general public, and c) continuously informing patients and the general public on project-related events, publications, downloads and newsworthy developments. Patient-relevant information will be made available in several common EU languages.

Project brochure (for patients, laymen and scientists) and professional templates

The project brochure will be a handy flyer or folder that summarises the project’s vision, why it matters, its key objectives, the partner institutions, basic facts (start date, duration, number of countries, funding amount etc.) for transparency, the website URL, and contact information of the scientific coordinator and the project Manager.

Video

A video will be produced for the general public and patients (target audience) explaining the problem of chronic pain and the secondary problems, the lack of adequate treatment for many chronic pain patients, as well as the key goals of the QSPainRelief project in form of animated filmed interviews with the coordinator and WP leaders.

Documents, reports (1)

Report on CNS drug distribution and target engagement profiles of all candidate drugs for augmentation strategies

Document identifying the selected drugs out of the list of EU approved medications their simulated CNS drug distribution and ontarget functional concentration derived from clinical studies

Publications

Peer reviewed articles (23)

Operant Self-medication for Assessment of Spontaneous Pain Relief and Drug Abuse Liability in Mouse Models of Chronic Pain

Author(s): David Cabañero, Beltrán Álvarez Pérez, Elena Martín-García, Rafael Maldonado
Published in: BIO-PROTOCOL, Issue 12, 2024, ISSN 2331-8325
Publisher: Bio-protocol
DOI: 10.21769/bioprotoc.4348

Structural Assessment of Agonist Efficacy in the μ-Opioid Receptor: Morphine and Fentanyl Elicit Different Activation Patterns

Author(s): Adrián Ricarte, James A. R. Dalton, Jesús Giraldo
Published in: Journal of Chemical Information and Modeling, Issue 61/3, 2021, Page(s) 1251-1274, ISSN 1549-9596
Publisher: American Chemical Society
DOI: 10.1021/acs.jcim.0c00890

A male mouse model of WIN 55,212–2 self-administration to study cannabinoid addiction

Author(s): María del Mar Cajiao-Manrique, Rafael Maldonado, Elena Martín-García
Published in: Frontiers in Pharmacology, Issue 14, 2023, ISSN 1663-9812
Publisher: Frontiers Media S.A.
DOI: 10.3389/fphar.2023.1143365

Role of CB2 cannabinoid receptor in the development of food addiction in male mice

Author(s): A. García-Blanco, Á. Ramírez-López, F. Navarrete, M.S. García-Gutiérrez, J. Manzanares, E. Martín-García, R. Maldonado
Published in: Neurobiology of Disease, Issue 179, 2024, Page(s) 106034, ISSN 0969-9961
Publisher: Academic Press
DOI: 10.1016/j.nbd.2023.106034

Dynamical Correlations Reveal Allosteric Sites in G Protein-Coupled Receptors

Author(s): Pedro Renault, Jesús Giraldo
Published in: International Journal of Molecular Sciences, Issue 22/1, 2021, Page(s) 187, ISSN 1422-0067
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms22010187

miRNA signatures associated with vulnerability to food addiction in mice and humans

Author(s): Alejandra García-Blanco, Laura Domingo-Rodriguez, Judit Cabana-Domínguez, Noèlia Fernández-Castillo, Laura Pineda-Cirera, Jordi Mayneris-Perxachs, Aurelijus Burokas, Jose Espinosa-Carrasco, Silvia Arboleya, Jessica Latorre, Catherine Stanton, Bru Cormand, Jose-Manuel Fernández-Real, Elena Martín-García, Rafael Maldonado
Published in: Journal of Clinical Investigation, Issue 132, 2023, ISSN 1558-8238
Publisher: The American Society for Clinical Investigation
DOI: 10.1172/jci156281

Presence of <i>Blastocystis</i> in gut microbiota is associated with cognitive traits and decreased executive function

Author(s): Jordi Mayneris-Perxachs, María Arnoriaga-Rodríguez, Josep Garre-Olmo, Josep Puig, Rafael Ramos, Maria Trelis, Aurelijus Burokas, Clàudia Coll, Cristina Zapata-Tona, Salvador Pedraza, Vicente Pérez-Brocal, Lluís Ramió, Wifredo Ricart, Andrés Moya, Mariona Jové, Joaquim Sol, Manuel Portero-Otin, Reinald Pamplona, Rafael Maldonado, José Manuel Fernández-Real
Published in: The ISME Journal, Issue 16, 2024, Page(s) 2181-2197, ISSN 1751-7362
Publisher: Nature Publishing Group
DOI: 10.1038/s41396-022-01262-3

Non‐linear blood–brain barrier transport and dosing strategies influence receptor occupancy ratios of morphine and its metabolites in pain matrix

Author(s): Divakar Budda, Berfin Gülave, J. G. Coen van Hasselt, Elizabeth C. M. de Lange
Published in: British Journal of Pharmacology, 2024, ISSN 0007-1188
Publisher: Wiley-Blackwell
DOI: 10.1111/bph.16394

Do P-glycoprotein-mediated drug-drug interactions at the blood-brain barrier impact morphine brain distribution?

Author(s): Berfin Gülave, Ariel Lesmana, Elizabeth CM de Lange, JG Coen van Hasselt
Published in: Journal of Pharmacokinetics and Pharmacodynamics, Issue 52, 2025, ISSN 1567-567X
Publisher: Kluwer Academic/Plenum Publishers
DOI: 10.1007/s10928-024-09957-0

Does nonlinear blood-brain barrier transport matter for (lower) morphine dosing strategies?

Author(s): Berfin Gülave, Divakar Budda, Mohammed AA Saleh, JG Coen van Hasselt, Elizabeth CM de Lange
Published in: European Journal of Pharmaceutical Sciences, Issue 187, 2024, Page(s) 106482, ISSN 0928-0987
Publisher: Elsevier BV
DOI: 10.1016/j.ejps.2023.106482

Beta-endorphin is the key endogenous opioid influencing morphine µ-opioid receptor occupancy in rat hypothalamus: a binding kinetic model analysis

Author(s): Divakar Budda, Zhicheng Zhang, J.G. Coen van Hasselt, Elizabeth C.M. de Lange
Published in: European Journal of Pharmaceutical Sciences, Issue 212, 2025, Page(s) 107195, ISSN 0928-0987
Publisher: Elsevier BV
DOI: 10.1016/j.ejps.2025.107195

Preoperative susceptibility to developing secondary hyperalgesia is associated with post‐thoracotomy pain at 2 months

Author(s): Solenn Gousset, Maximilien Cappe, Cedric Lenoir, Arnaud Steyaert, Patricia Lavand'homme, André Mouraux, Valérie Lacroix, Emanuel N. van den Broeke
Published in: European Journal of Pain, Issue 29, 2025, ISSN 1090-3801
Publisher: W. B. Saunders Co., Ltd.
DOI: 10.1002/ejp.4768

Evaluating Allosteric Perturbations in Cannabinoid Receptor 1 by In Silico Single-Point Mutation.

Author(s): Oscar Díaz, Pedro Renault, and Jesús Giraldo
Published in: ACS Omega, Issue 7, 42, 2022, Page(s) 37873–37884, ISSN 2470-1343
Publisher: American Chemical Society (ACS) Publications
DOI: 10.1021/acsomega.2c04980

Using the LeiCNS-PK3.0 Physiologically-Based Pharmacokinetic Model to Predict Brain Extracellular Fluid Pharmacokinetics in Mice

Author(s): Mohammed A. A. Saleh, Berfin Gülave, Olivia Campagne, Clinton F. Stewart, Jeroen Elassaiss-Schaap, Elizabeth C. M. de Lange
Published in: Pharmaceutical Research, Issue 40, 2023, Page(s) 2555-2566, ISSN 0724-8741
Publisher: Kluwer Academic/Plenum Publishers
DOI: 10.1007/s11095-023-03554-5

Navigating the biopsychosocial landscape: A systematic review on the association between social support and chronic pain

Author(s): Carlo Matej Rinaudo, Maxim Van de Velde, Arnaud Steyaert, André Mouraux
Published in: PLOS One, Issue 20, 2025, Page(s) e0321750, ISSN 1932-6203
Publisher: Public Library of Science
DOI: 10.1371/journal.pone.0321750

Application of a Nociceptive Test Battery to Assess Potential Synergy between Two Analgesics in Healthy Subjects

Author(s): Wouter Alexander Bakker, Monir Bertayli, Daniël Benjamin Dumas, Jeroen Elassaiss-Schaap, Maria Joanna Juachon, Karen Broekhuizen, Hemme Jacob Hijma, Geert Jan Groeneveld
Published in: ACS Pharmacology &amp; Translational Science, Issue 8, 2025, Page(s) 819-830, ISSN 2575-9108
Publisher: American Chemical Society (ACS)
DOI: 10.1021/acsptsci.4c00696

THC exposure during adolescence increases impulsivity-like behavior in adulthood in a WIN 55,212-2 self-administration mouse model

Author(s): María del Mar Cajiao-Manrique, Verònica Casadó-Anguera, Alejandra García-Blanco, Rafael Maldonado, Elena Martín-García
Published in: Frontiers in Psychiatry, Issue 14, 2023, ISSN 1664-0640
Publisher: Frontiers Research Foundation
DOI: 10.3389/fpsyt.2023.1148993

Time-dependent ligand-receptor binding kinetics and functionality in a heterodimeric receptor model

Author(s): Antonio J. Ortiz, Víctor Martín, David Romero, Antoni Guillamon, Jesús Giraldo
Published in: Biochemical Pharmacology, Issue 225, 2024, Page(s) 116299, ISSN 0006-2952
Publisher: Elsevier BV
DOI: 10.1016/j.bcp.2024.116299

Allosteric binding cooperativity in a kinetic context

Author(s): Óscar Díaz, Victor Martín, Pedro Renault, David Romero, Antoni Guillamon, Jesús Giraldo
Published in: Drug Discovery Today, Issue Volume 28, Issue 2, 2023, ISSN 1359-6446
Publisher: Elsevier BV
DOI: 10.1016/j.drudis.2022.103441

Does nonlinear blood-brain barrier transport matter for morphine dosing strategies?

Author(s): Berfin Gülave; Divakar Budda; Mohammed AA Saleh; JG Coen van Hasselt; Elizabeth CM de Lange
Published in: European Journal of Pharmaceutical Sciences, 2023, ISSN 0928-0987
Publisher: Elsevier BV
DOI: 10.1101/2023.03.17.533135

Reliability of in vitro data for the mechanistic prediction of brain extracellular fluid pharmacokinetics of P-glycoprotein substrates in vivo; are we scaling correctly?

Author(s): Daan W. van Valkengoed, Makoto Hirasawa, Vivi Rottschäfer, Elizabeth C. M. de Lange
Published in: Journal of Pharmacokinetics and Pharmacodynamics, Issue 52, 2025, ISSN 1567-567X
Publisher: Kluwer Academic/Plenum Publishers
DOI: 10.1007/s10928-025-09963-w

Statistics for the analysis of molecular dynamics simulations: providing P values for agonist-dependent GPCR activation

Author(s): Agustín Bruzzese, James A. R. Dalton, Jesús Giraldo
Published in: Scientific Reports, Issue 10/1, 2020, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/s41598-020-77072-4

Prediction of the Extent of Blood–Brain Barrier Transport Using Machine Learning and Integration into the LeiCNS-PK3.0 Model

Author(s): Berfin Gülave, Helle W. van den Maagdenberg, Luke van Boven, Gerard J. P. van Westen, Elizabeth C. M. de Lange, J. G. Coen van Hasselt
Published in: Pharmaceutical Research, Issue 42, 2025, Page(s) 281-289, ISSN 0724-8741
Publisher: Kluwer Academic/Plenum Publishers
DOI: 10.1007/s11095-025-03828-0

Conference proceedings (1)

PK-PD model of morphine, pregabalin and their combination to assess the opioid-sparing effect

Author(s): Monir Bertayli, Wouter Bakker, Geert Jan Groeneveld, Jeroen Elassaiss-Schaap
Published in: Poster Abstract, 2024
Publisher: PAGE

Thesis and dissertations (1)

Novel approaches to investigate central sensitization : from experimental models to clinical perspectives

Author(s): Gousset, Solenn
Published in: DIAL.pr Research Publications, 2025
Publisher: UCL - SSS/IONS/COSY - Systems & cognitive Neuroscience