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Updated: Jun 20, 2026
Determining Pain Detection and Tolerance Thresholds Using an Integrated, Multi-Modal Pain Task Battery
Published on: April 14, 2016
Use of sensory methods for detecting target engagement in clinical trials of new analgesics
Boris A Chizh1, Christine N Sang
1GlaxoSmithKline, Addenbrooke's Centre for Clinical Investigation, Addenbrooke's Hospital, Cambridge CB2 2GG, United Kingdom. boris.a.chizh@gsk.com
Abstract:
The translation of analgesic efficacy seen in preclinical pain models into the clinic is problematic and is associated with a number of factors that may result in the failure of clinical trials to detect the effect of investigational therapeutic agents. The use of translational pain biomarkers in phase I trials can potentially reduce some of these risks by measuring the interaction between the drug and its target (termed target engagement) in humans. To serve this purpose, sensory tests and other measures of pharmacological activity in nociceptive pathways need to be identified, based on the preclinical profile of the drug being tested and the feasibility of human assessments. Here we discuss some examples to assess the utility of sensory and related pain biomarkers in the early phase of evaluation of novel analgesics for confirmation of target engagement in humans. The emphasis is on the TRPV1 antagonists, but some other target mechanisms are also discussed in examining the validity of this approach.
Insights
Translational pain biomarkers, such as sensory tests, can confirm drug target engagement in early human trials. This approach helps validate novel analgesics and reduces clinical trial failures in pain management.
Area of Science:
- Neuroscience
- Pharmacology
- Clinical Trials
Background:
- Translating preclinical analgesic efficacy to clinical success is challenging.
- Clinical trials often fail to detect therapeutic effects of novel pain agents.
- Early confirmation of drug-target interaction in humans is crucial.
Purpose of the Study:
- To evaluate the utility of translational pain biomarkers in early-phase clinical trials.
- To confirm target engagement of novel analgesics in humans.
- To reduce risks associated with clinical trial failures.
Main Methods:
- Identifying sensory tests and pharmacological measures of nociceptive pathways.
- Assessing biomarkers based on preclinical drug profiles and human assessment feasibility.
- Focusing on TRPV1 antagonists and other target mechanisms.
Main Results:
- Sensory and related pain biomarkers can confirm target engagement in early human studies.
- This approach aids in validating novel analgesic mechanisms.
- Examples include assessments for TRPV1 antagonists.
Conclusions:
- Translational pain biomarkers are valuable tools for early analgesic drug development.
- Confirming target engagement enhances the reliability of clinical trial outcomes.
- This strategy improves the efficiency of identifying effective pain therapeutics.
