A reappraisal of peripheral pain pathways (360G-Wellcome-200183_Z_15_Z)

Action potential propagation velocity provided a useful system for categorising peripheral nerves for 75 years. Now, genetic definition of sensory neuron subsets is providing a more precise functional distinction; individual sensory neurons and their target dorsal horn neurons can be activated, silenced or killed genetically and defined in terms of their transcriptomes, and linked to behavioural changes. In addition, physiological stimuli can be used to drive activity dependent reporters allowing further definition of neuronal subtypes. In this proposal, we show how the exploitation of these methods will inform our knowledge of peripheral pain pathways, the key element in almost all chronic pain syndromes, and identify cell types and molecular targets that are critical for distinct types of pain sensation. Our work will encompass human and animal genetics and should provide clinically significant information.