Nociceptive sensory neurons, which convey environmental stimuli indicating real or potentially tissue-damaging events, undergo plastic changes in phenotype in response to prolonged or intense noxious stimulation. These changes represent an essential component of the chronic painful hypersensitivity of pathological pain. Particularly important is the possibility that non- nociceptive neurons may also undergo changes in phenotype in response to tissue injury, resulting in the perception of even light touch as painful. Currently, it is not clear how noxious stimuli result in changes in sensory neuron gene expression. Efforts to address these issues are hampered by the difficulty of determining the modalities of sensory neurons in preparations in which the effects of stimulation can be effectively addressed. Several techniques have been established in this laboratory to identify and isolate specfic populations of nociceptors and non- nociceptive mechansensors. Experiments described here will examine the ability of different qualities of noxious stimulation to activate transcription in sensory neurons both in vivo and in vitro. Finally, the ability to identify innocuous mechanoreceptors will allow us to definitively determine whether noxious stimulation is capable of activating gene expression in non-nociceptive sensory neurons.