Nociception in fruit fly larvae.

Nociception, the process of encoding and processing noxious or painful stimuli, allows animals to detect and avoid or escape from potentially life-threatening stimuli. Here, we provide a brief overview of recent technical developments and studies that have advanced our understanding of the larval nociceptive circuit and demonstrated its potential as a model system to elucidate the mechanistic basis of nociception. The nervous system of a larva contains roughly 15,000 neurons, which allows for reconstructing the connectivity among them directly by transmission electron microscopy. In addition, the availability of genetic tools for manipulating the activity of individual neurons and recent advances in computational and high-throughput behavior analysis methods have facilitated the identification of a neural circuit underlying a characteristic nocifensive behavior. We also discuss how neuromodulators may play a key role in modulating the nociceptive circuit and behavioral output. A detailed understanding of the structure and function of larval nociceptive neural circuit could provide insights into the organization and operation of pain circuits in mammals and generate new knowledge to advance the development of treatment options for pain in humans.