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Pharmacological Probes to Validate Biomarkers for Analgesic Drug Development

There is an urgent need for analgesics with improved efficacy, especially in neuropathic and other chronic pain conditions. Unfortunately, in recent decades, many candidate analgesics have failed in clinical phase II or III trials despite promising preclinical results. Translational assessment tools...

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Autores principales: van Niel, Johannes, Bloms-Funke, Petra, Caspani, Ombretta, Cendros, Jose Maria, Garcia-Larrea, Luis, Truini, Andrea, Tracey, Irene, Chapman, Sonya C., Marco-Ariño, Nicolás, Troconiz, Iñaki F., Phillips, Keith, Finnerup, Nanna Brix, Mouraux, André, Treede, Rolf-Detlef
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368481/
https://www.ncbi.nlm.nih.gov/pubmed/35955432
http://dx.doi.org/10.3390/ijms23158295
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author van Niel, Johannes
Bloms-Funke, Petra
Caspani, Ombretta
Cendros, Jose Maria
Garcia-Larrea, Luis
Truini, Andrea
Tracey, Irene
Chapman, Sonya C.
Marco-Ariño, Nicolás
Troconiz, Iñaki F.
Phillips, Keith
Finnerup, Nanna Brix
Mouraux, André
Treede, Rolf-Detlef
author_facet van Niel, Johannes
Bloms-Funke, Petra
Caspani, Ombretta
Cendros, Jose Maria
Garcia-Larrea, Luis
Truini, Andrea
Tracey, Irene
Chapman, Sonya C.
Marco-Ariño, Nicolás
Troconiz, Iñaki F.
Phillips, Keith
Finnerup, Nanna Brix
Mouraux, André
Treede, Rolf-Detlef
author_sort van Niel, Johannes
collection PubMed
description There is an urgent need for analgesics with improved efficacy, especially in neuropathic and other chronic pain conditions. Unfortunately, in recent decades, many candidate analgesics have failed in clinical phase II or III trials despite promising preclinical results. Translational assessment tools to verify engagement of pharmacological targets and actions on compartments of the nociceptive system are missing in both rodents and humans. Through the Innovative Medicines Initiative of the European Union and EFPIA, a consortium of researchers from academia and the pharmaceutical industry was established to identify and validate a set of functional biomarkers to assess drug-induced effects on nociceptive processing at peripheral, spinal and supraspinal levels using electrophysiological and functional neuroimaging techniques. Here, we report the results of a systematic literature search for pharmacological probes that allow for validation of these biomarkers. Of 26 candidate substances, only 7 met the inclusion criteria: evidence for nociceptive system modulation, tolerability, availability in oral form for human use and absence of active metabolites. Based on pharmacokinetic characteristics, three were selected for a set of crossover studies in rodents and healthy humans. All currently available probes act on more than one compartment of the nociceptive system. Once validated, biomarkers of nociceptive signal processing, combined with a pharmacometric modelling, will enable a more rational approach to selecting dose ranges and verifying target engagement. Combined with advances in classification of chronic pain conditions, these biomarkers are expected to accelerate analgesic drug development.
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spelling pubmed-93684812022-08-12 Pharmacological Probes to Validate Biomarkers for Analgesic Drug Development van Niel, Johannes Bloms-Funke, Petra Caspani, Ombretta Cendros, Jose Maria Garcia-Larrea, Luis Truini, Andrea Tracey, Irene Chapman, Sonya C. Marco-Ariño, Nicolás Troconiz, Iñaki F. Phillips, Keith Finnerup, Nanna Brix Mouraux, André Treede, Rolf-Detlef Int J Mol Sci Review There is an urgent need for analgesics with improved efficacy, especially in neuropathic and other chronic pain conditions. Unfortunately, in recent decades, many candidate analgesics have failed in clinical phase II or III trials despite promising preclinical results. Translational assessment tools to verify engagement of pharmacological targets and actions on compartments of the nociceptive system are missing in both rodents and humans. Through the Innovative Medicines Initiative of the European Union and EFPIA, a consortium of researchers from academia and the pharmaceutical industry was established to identify and validate a set of functional biomarkers to assess drug-induced effects on nociceptive processing at peripheral, spinal and supraspinal levels using electrophysiological and functional neuroimaging techniques. Here, we report the results of a systematic literature search for pharmacological probes that allow for validation of these biomarkers. Of 26 candidate substances, only 7 met the inclusion criteria: evidence for nociceptive system modulation, tolerability, availability in oral form for human use and absence of active metabolites. Based on pharmacokinetic characteristics, three were selected for a set of crossover studies in rodents and healthy humans. All currently available probes act on more than one compartment of the nociceptive system. Once validated, biomarkers of nociceptive signal processing, combined with a pharmacometric modelling, will enable a more rational approach to selecting dose ranges and verifying target engagement. Combined with advances in classification of chronic pain conditions, these biomarkers are expected to accelerate analgesic drug development. MDPI 2022-07-27 /pmc/articles/PMC9368481/ /pubmed/35955432 http://dx.doi.org/10.3390/ijms23158295 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
van Niel, Johannes
Bloms-Funke, Petra
Caspani, Ombretta
Cendros, Jose Maria
Garcia-Larrea, Luis
Truini, Andrea
Tracey, Irene
Chapman, Sonya C.
Marco-Ariño, Nicolás
Troconiz, Iñaki F.
Phillips, Keith
Finnerup, Nanna Brix
Mouraux, André
Treede, Rolf-Detlef
Pharmacological Probes to Validate Biomarkers for Analgesic Drug Development
title Pharmacological Probes to Validate Biomarkers for Analgesic Drug Development
title_full Pharmacological Probes to Validate Biomarkers for Analgesic Drug Development
title_fullStr Pharmacological Probes to Validate Biomarkers for Analgesic Drug Development
title_full_unstemmed Pharmacological Probes to Validate Biomarkers for Analgesic Drug Development
title_short Pharmacological Probes to Validate Biomarkers for Analgesic Drug Development
title_sort pharmacological probes to validate biomarkers for analgesic drug development
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368481/
https://www.ncbi.nlm.nih.gov/pubmed/35955432
http://dx.doi.org/10.3390/ijms23158295
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