Pharmacological probes to validate biomarkers for analgesic drug development

• Verfasst von: Van Niel, Johannes [VerfasserIn]
• Verfasst von: Bloms-Funke, Petra [VerfasserIn]
• Verfasst von: Caspani, Ombretta [VerfasserIn]
• Verfasst von: Cendros, Jose Maria [VerfasserIn]
• Verfasst von: Garcia-Larrea, Luis [VerfasserIn]
• Verfasst von: Truini, Andrea [VerfasserIn]
• Verfasst von: Tracey, Irene [VerfasserIn]
• Verfasst von: Chapman, Sonya C. [VerfasserIn]
• Verfasst von: Marco-Ariño, Nicolás [VerfasserIn]
• Verfasst von: Troconiz, Iñaki F. [VerfasserIn]
• Verfasst von: Phillips, Keith [VerfasserIn]
• Verfasst von: Finnerup, Nanna Brix [VerfasserIn]
• Verfasst von: Mouraux, André [VerfasserIn]
• Verfasst von: Treede, Rolf-Detlef [VerfasserIn]
• Titel: Pharmacological probes to validate biomarkers for analgesic drug development
• Verf.angabe: Johannes van Niel, Petra Bloms-Funke, Ombretta Caspani, Jose Maria Cendros, Luis Garcia-Larrea, Andrea Truini, Irene Tracey, Sonya C. Chapman, Nicolás Marco-Ariño, Iñaki F. Troconiz, Keith Phillips, Nanna Brix Finnerup, André Mouraux and Rolf-Detlef Treede
• E-Jahr: 2022
• Jahr: 27 July 2022
• Umfang: 16 S.
• Fussnoten: Gesehen am 27.08.2024
• Schrift/Sprache: Titel des übergeordneten Special issue: Pharmacology in pain management
• Titel Quelle: Enthalten in: International journal of molecular sciences
• Ort Quelle: Basel : Molecular Diversity Preservation International, 2000
• Jahr Quelle: 2022
• Band/Heft Quelle: 23(2022), 15, Artikel-ID 8295, Seite 1-16
• ISSN Quelle: 1422-0067
• ISSN Quelle: 1661-6596
• DOI: doi:10.3390/ijms23158295
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: analgesic
• Sach-SW: biomarkers
• Sach-SW: drug development
• Sach-SW: pain
• Sach-SW: PK/PD
• Sach-SW: proof of concept
• Sach-SW: proof of mechanism
• K10plus-PPN: 1899580824

Abstract

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.