Nociception is critical for protecting animals from tissue damage. It is also involved in many biological and pathological processes. However, the underlying molecular and cellular mechanisms are underexplored. Drosophila larvae display food-averse behaviors at the end of third-instar stage, providing a unique opportunity to delineate the neurobiological basis of age-restricted response to aversive / stressful environmental stimuli. Here we provided evidences for a fructose-responsive chemosensory pathway that modulates food-averse migratory and social behaviors. painless (pain), a transient receptor potential (TRP) channel that is responsive to noxious stimuli, is required for the fructose response. A subset of pain-expressing sensory neurons have been identified that show PAIN-dependent excitation by fructose. We also found that the developmental switch from food attraction to aversion is regulated by Neuropeptide F, a neuropeptide Y (NPY)-related signaling peptide. NPF, like mammalian opioids and endocannabinoids, suppresses peripheral noxious stimulation through its G-protein coupled receptor NPFR1. NPF / NPFR1 signaling negatively modulates different subtypes of fly and mammalian TRP-family ion channels expressed in larval sensory neurons. In human cells, NPFR1 attenuates TRPV1-mediated Ca2+ influx and its enhancement by cAMP analogs. Similarly, the NPF / NPFR1 pathway also blocks sensitization of larval aversive response by cAMP-dependent protein kinase (PKA).Drosophila post-feeding larvae also display food-averse social burrowing to through food proper to migrate towards food-free pupation sites. We show that the social burrowing is comprised of three genetically separable behaviors, seeking, clumping and burrowing. The PKA activities in a subset of pain-expressing neurons are essential for the onset of seeking, clumping and burrowing behaviors. Meanwhile, PKA in atonal-expressing neurons and a subset of Va neurons differentially regulate clumping but not seeking and burrowing activity. Taken together, we provided the first molecular and genetic evidences for a complex neuronal network for developmental regulation of sugar-averse behaviors in post-feeding Drosophila larvae, comprised of a conserved nociceptive module containing TRPA channel PAIN, and a temporal control module containing conserved NPY family peptide NPF. In the long term, our Drosophila larva model will not only serve as an excellent model for studying molecular and cellular mechanisms of nociception, but also help in identifying novel nociceptive genes and gaining insights into pain mechanisms of higher organisms.