Target Identification Strategies in the Genomic Era

William R. Lariviere, PhD

Assistant Professor of Anesthesiology
University of Pittsburgh School of Medicine
Pittsburgh, Pennsylvania

Although the subjective nature of pain complicates reproducing and analyzing experiment pain in animal models, preclinical pain research has led to significant progress in clinical pain management. In particular, scientific studies have improved our understanding of the neural underpinnings of pain—with significant implications for assessment and treatment—and led to new pharmacologic and interventional pain management approaches. Current research is taking advantage of the superior genotypic and environmental control associated with animal models to examine the mechanisms of pain-related heritability, how pain traits relate to one another, and new molecular targets for drug discovery. Interestingly, various groups have reported that 50%–70% of the variability among individuals in pain perception traits results from genetic factors. Moreover, heritability of pain sensitivity is highly dependent on the particular pain modality (eg, thermal or inflammatory). Ongoing efforts are now using integrative genomic and gene expression approaches to identify candidate genes associated with specific pain traits, which can then be translated into clinical applications and novel drug development. Here, Dr. Lariviere discusses the heritability of pain-related traits, genomic techniques to identify therapeutic targets, and how recent findings may lead to improved analgesic strategies.

References

1. Nair HK, Hain H, Quock RM, et al. Genomic loci and candidate genes underlying inflammatory nociception. Pain. 2011;152(3):599-606.
2. Lariviere WR, Mogil JS. The genetics of pain and analgesia in laboratory animals. Methods Mol Biol. 2010;617:261-278.
3. Mao J. Translational pain research: achievements and challenges. J Pain. 2009;10:1001-1011.

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