In vitro models for neuropathic pain phenotypic screening in brain therapeutics

Area of Science:

• Neuroscience
• Pharmacology
• Drug Discovery

Background:

• Preclinical to clinical translation of brain therapeutics remains a significant challenge.
• Neuronal models are crucial for phenotypic screening to identify active compounds without target knowledge.
• Neuropathic pain research specifically requires more translatable models.

Approach:

• This review provides an overview of existing neuronal models for drug discovery.
• It examines the strengths and limitations of these models in neuropathic pain research.
• A comparative analysis is presented for screening strategies, model validation, and target deconvolution.

Key Points:

• Phenotypic screening using translatable neuronal models can overcome preclinical-to-clinical translation issues.
• Models are evaluated for their utility in developing novel screening strategies for neuropathic pain.
• The review covers model validation for primary/secondary assays and their application in target deconvolution.

Conclusions:

• Improved neuronal models are essential for advancing brain therapeutic discovery, particularly for neuropathic pain.
• This work highlights the importance of phenotypic screening and model validation in identifying effective treatments.
• The discussed models offer a pathway to more successful drug development pipelines.