Pathobiology of Visceral Pain: Molecular Mechanisms and Therapeutic Implications II. Genetic approaches to pain therapy

New analgesic drugs are necessary because a number of pain states are untre atable. Genetic approaches to the identification of analgesic drug targets include mapping genes involved in human pain perception (e.g., trkA involve d in hereditary neuropathies), identifying regulators of sensory neuron fun ction in simple multicellular organisms and then investigating the activity of their mammalian homologs (e.g., POU domain transcription factors that s pecify sensory cell fate), as well as difference, expression, and homology cloning of receptors, ion channels, and transcription factors present in se nsory neurons. After target validation through the construction of null mut ant mice, high-throughput cell-based screens can be used tio identify poten tial drug candidates. As a result of these approaches, a number of receptor s and ion channels present in sensory neurons such as voltage-gated sodium channels [sensory neuron specific (SNS) and Na channel novel] and ATP-gated (P2X3), capsaicin-gated [vanilloid receptor 1(VR1)], and proton-gated [aci d-sensing ion channel (ASIC)] channels are now under investigation as poten tial new analgesic drug targets.