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

Información del proyecto

QSPainRelief

Identificador del acuerdo de subvención: 848068

DOI

10.3030/848068

Proyecto cerrado

Fecha de la firma de la CE 13 Diciembre 2019

Fecha de inicio 1 Enero 2020

Fecha de finalización 30 Junio 2025

Financiado con arreglo a

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

Coste total

€ 6 239 539,25

Aportación de la UE

€ 6 239 538,75

Coordinado por

UNIVERSITEIT LEIDEN
Netherlands

CORDIS proporciona enlaces a los documentos públicos y las publicaciones de los proyectos de los programas marco HORIZONTE.

Los enlaces a los documentos y las publicaciones de los proyectos del Séptimo Programa Marco, así como los enlaces a algunos tipos de resultados específicos, como conjuntos de datos y «software», se obtienen dinámicamente de OpenAIRE .

Resultado final

Other (4)

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.

MVR and CUI public database

This deliverable will be a database summarizing MVR and CUI model results. The results will be fed into a public database for Dissemination.

Dissemination-ready database

The database ready for dissemination will be made available to WP9 to be part of an open data repository.

Documents, reports (6)

Report on status of posting results, including clinical study report QSPainRelief-novelA

Report on the status of posting results in the study registry/ies (including timelines when final posting of results is scheduled after end of funding period). It will also include the information on the final recruitment pace and risk mitigation strategies for the QSPainRelief-novel A complete clinical study.

White paper on new effective combinational treatment of chronic pain in individual patients

The QSPainRelief consortium will write a white paper with the QSPainRelief consortium vision on how to have better effective combinational treatment of chronic pain in individual patients.

Protocol for future prospective clinical trial (for the best combination)

Fully documented computer model of neuronal circuits involved in human analgesia, drug abuse liability, sedation & cognitive impairment, calibrated with existing clinical data.

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 on-target functional concentration derived from clinical studies.

Updated clinical practice guidance document on to be avoided combinational treatment of chronic pain in individual patients

A clinical practice guidance for physicians and other health care providers will be written, with recommendations to drive the European, national and also global guidelines for management of patients with chronic pain.

Ethical final report on the ethics needs for pre- and clinical studies

This document will list all the suggestions potentially raised by the Ethic Advisory Board as well as the ethic-related needs identified along project development and implementation. This deliverable will also summarize all the activities carried out at the beginning of the project, or after the periodical reassessments of ethic needs, to assess all the ethic-related issues and to ensure that they have been properly managed in full respect of laws and ethic requirements.

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.

Publicaciones

Peer reviewed articles (23)

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

Autores: David Cabañero, Beltrán Álvarez Pérez, Elena Martín-García, Rafael Maldonado
Publicado en: BIO-PROTOCOL, Edición 12, 2024, ISSN 2331-8325
Editor: Bio-protocol
DOI: 10.21769/bioprotoc.4348

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

Autores: Adrián Ricarte, James A. R. Dalton, Jesús Giraldo
Publicado en: Journal of Chemical Information and Modeling, Edición 61/3, 2021, Página(s) 1251-1274, ISSN 1549-9596
Editor: American Chemical Society
DOI: 10.1021/acs.jcim.0c00890

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

Autores: María del Mar Cajiao-Manrique, Rafael Maldonado, Elena Martín-García
Publicado en: Frontiers in Pharmacology, Edición 14, 2023, ISSN 1663-9812
Editor: Frontiers Media S.A.
DOI: 10.3389/fphar.2023.1143365

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

Autores: A. García-Blanco, Á. Ramírez-López, F. Navarrete, M.S. García-Gutiérrez, J. Manzanares, E. Martín-García, R. Maldonado
Publicado en: Neurobiology of Disease, Edición 179, 2024, Página(s) 106034, ISSN 0969-9961
Editor: Academic Press
DOI: 10.1016/j.nbd.2023.106034

Dynamical Correlations Reveal Allosteric Sites in G Protein-Coupled Receptors

Autores: Pedro Renault, Jesús Giraldo
Publicado en: International Journal of Molecular Sciences, Edición 22/1, 2021, Página(s) 187, ISSN 1422-0067
Editor: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms22010187

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

Autores: 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
Publicado en: Journal of Clinical Investigation, Edición 132, 2023, ISSN 1558-8238
Editor: 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

Autores: 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
Publicado en: The ISME Journal, Edición 16, 2024, Página(s) 2181-2197, ISSN 1751-7362
Editor: 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

Autores: Divakar Budda, Berfin Gülave, J. G. Coen van Hasselt, Elizabeth C. M. de Lange
Publicado en: British Journal of Pharmacology, 2024, ISSN 0007-1188
Editor: Wiley-Blackwell
DOI: 10.1111/bph.16394

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

Autores: Berfin Gülave, Ariel Lesmana, Elizabeth CM de Lange, JG Coen van Hasselt
Publicado en: Journal of Pharmacokinetics and Pharmacodynamics, Edición 52, 2025, ISSN 1567-567X
Editor: Kluwer Academic/Plenum Publishers
DOI: 10.1007/s10928-024-09957-0

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

Autores: Berfin Gülave, Divakar Budda, Mohammed AA Saleh, JG Coen van Hasselt, Elizabeth CM de Lange
Publicado en: European Journal of Pharmaceutical Sciences, Edición 187, 2024, Página(s) 106482, ISSN 0928-0987
Editor: 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

Autores: Divakar Budda, Zhicheng Zhang, J.G. Coen van Hasselt, Elizabeth C.M. de Lange
Publicado en: European Journal of Pharmaceutical Sciences, Edición 212, 2025, Página(s) 107195, ISSN 0928-0987
Editor: Elsevier BV
DOI: 10.1016/j.ejps.2025.107195

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

Autores: Solenn Gousset, Maximilien Cappe, Cedric Lenoir, Arnaud Steyaert, Patricia Lavand'homme, André Mouraux, Valérie Lacroix, Emanuel N. van den Broeke
Publicado en: European Journal of Pain, Edición 29, 2025, ISSN 1090-3801
Editor: W. B. Saunders Co., Ltd.
DOI: 10.1002/ejp.4768

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

Autores: Oscar Díaz, Pedro Renault, and Jesús Giraldo
Publicado en: ACS Omega, Edición 7, 42, 2022, Página(s) 37873–37884, ISSN 2470-1343
Editor: 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

Autores: Mohammed A. A. Saleh, Berfin Gülave, Olivia Campagne, Clinton F. Stewart, Jeroen Elassaiss-Schaap, Elizabeth C. M. de Lange
Publicado en: Pharmaceutical Research, Edición 40, 2023, Página(s) 2555-2566, ISSN 0724-8741
Editor: 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

Autores: Carlo Matej Rinaudo, Maxim Van de Velde, Arnaud Steyaert, André Mouraux
Publicado en: PLOS One, Edición 20, 2025, Página(s) e0321750, ISSN 1932-6203
Editor: 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

Autores: Wouter Alexander Bakker, Monir Bertayli, Daniël Benjamin Dumas, Jeroen Elassaiss-Schaap, Maria Joanna Juachon, Karen Broekhuizen, Hemme Jacob Hijma, Geert Jan Groeneveld
Publicado en: ACS Pharmacology &amp; Translational Science, Edición 8, 2025, Página(s) 819-830, ISSN 2575-9108
Editor: 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

Autores: María del Mar Cajiao-Manrique, Verònica Casadó-Anguera, Alejandra García-Blanco, Rafael Maldonado, Elena Martín-García
Publicado en: Frontiers in Psychiatry, Edición 14, 2023, ISSN 1664-0640
Editor: Frontiers Research Foundation
DOI: 10.3389/fpsyt.2023.1148993

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

Autores: Antonio J. Ortiz, Víctor Martín, David Romero, Antoni Guillamon, Jesús Giraldo
Publicado en: Biochemical Pharmacology, Edición 225, 2024, Página(s) 116299, ISSN 0006-2952
Editor: Elsevier BV
DOI: 10.1016/j.bcp.2024.116299

Allosteric binding cooperativity in a kinetic context

Autores: Óscar Díaz, Victor Martín, Pedro Renault, David Romero, Antoni Guillamon, Jesús Giraldo
Publicado en: Drug Discovery Today, Edición Volume 28, Edición 2, 2023, ISSN 1359-6446
Editor: Elsevier BV
DOI: 10.1016/j.drudis.2022.103441

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

Autores: Berfin Gülave; Divakar Budda; Mohammed AA Saleh; JG Coen van Hasselt; Elizabeth CM de Lange
Publicado en: European Journal of Pharmaceutical Sciences, 2023, ISSN 0928-0987
Editor: 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?

Autores: Daan W. van Valkengoed, Makoto Hirasawa, Vivi Rottschäfer, Elizabeth C. M. de Lange
Publicado en: Journal of Pharmacokinetics and Pharmacodynamics, Edición 52, 2025, ISSN 1567-567X
Editor: 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

Autores: Agustín Bruzzese, James A. R. Dalton, Jesús Giraldo
Publicado en: Scientific Reports, Edición 10/1, 2020, ISSN 2045-2322
Editor: 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

Autores: 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
Publicado en: Pharmaceutical Research, Edición 42, 2025, Página(s) 281-289, ISSN 0724-8741
Editor: 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

Autores: Monir Bertayli, Wouter Bakker, Geert Jan Groeneveld, Jeroen Elassaiss-Schaap
Publicado en: Poster Abstract, 2024
Editor: PAGE

Thesis and dissertations (1)

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

Autores: Gousset, Solenn
Publicado en: DIAL.pr Research Publications, 2025
Editor: UCL - SSS/IONS/COSY - Systems & cognitive Neuroscience