Evidence map›Paper›PMID 35955432›Full record

SynthesisInternational journal of molecular sciences2022

Pharmacological Probes to Validate Biomarkers for Analgesic Drug Development.

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 and 4 more

Open access · goldAbstract readSystematic Review
In one paragraph

Synthesis in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.5field-weighted citation impact, top 38% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 4 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 9 institutions in 7 countries.

Johannes van NielMature Products Develoment, Grünenthal GmbH, 52099 Aachen, Germany.
Petra Bloms-FunkeTranslational Science & Intelligence, Grünenthal GmbH, 52099 Aachen, Germany.
Ombretta CaspaniMannheim Center for Translational Neurosciences (MCTN), Department of Neurophysiology, University of Heidelberg, 69120 Mannheim, Germany.
Jose Maria CendrosDevelopment DMPK, Welab Barcelona, 08028 Barcelona, Spain.ORCID 0000-0002-4437-7585
Luis Garcia-LarreaLyon Neurosciences Center Research Unit Inserm U 1028, Pierre Wertheimer Hospital, Hospices Civils de Lyon, Lyon 1 University, 69100 Lyon, France.ORCID 0000-0002-9873-789X
Andrea TruiniDepartment of Human Neuroscience, Sapienzia University, 00185 Rome, Italy.
Irene TraceyWellcome Centre for Integrative Neuroimaging, FMRIB Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Sonya C ChapmanEli Lilly and Company, Arlington Square, Bracknell RG12 1PU, UK.
Nicolás Marco-AriñoDepartment of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, University of Navarra, 31009 Pamplona, Spain.ORCID 0000-0002-3526-8037
Iñaki F TroconizDepartment of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, University of Navarra, 31009 Pamplona, Spain.ORCID 0000-0003-3700-8658
Keith PhillipsEli Lilly and Company, Erl Wood, Bracknell GU20 6PH, UK.
Nanna Brix FinnerupDanish Pain Research Center, Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark.ORCID 0000-0001-5541-0240
André MourauxInstitute of Neuroscience (IoNS), UCLouvain, B-1200 Brussels, Belgium.
Rolf-Detlef TreedeMannheim Center for Translational Neurosciences (MCTN), Department of Neurophysiology, University of Heidelberg, 69120 Mannheim, Germany.
Eli Lilly (United Kingdom) · GBGrünenthal Group (Germany) · DEHeidelberg University · DEUniversidad de Navarra · ESAarhus University · DKJohn Radcliffe Hospital · GBSapienza University of Rome · ITUCLouvain · BEUniversité Claude Bernard Lyon 1 · FR

Funding

Innovative Medicines Initiative 777500
6 · The paper itself

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.

Indexed as

AnalgesicsBiomarkers, PharmacologicalDrug DevelopmentChronic PainHumansNeuralgiaReproducibility of ResultsSpineAnalgesicsBiomarkers, Pharmacologicalanalgesicbiomarkersdrug developmentpainPK/PDproof of conceptproof of mechanism

Identifiers

PMID35955432
PMCPMC9368481
OpenAlexW4288067447

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.