The interaction of octopamine and neuropeptides to slow aversive responses in C. elegans mimics the modulation of chronic pain in mammals.

Octopamine (OA) appears to function as the invertebrate counterpart of norepinephrine (NE) in the modulation of a number of key behaviors. In C. elegans, OA signaling is complex, mediated by at least three distinct α-adrenergic-like receptors and appears to activate more global peptidergic signaling cascades that have the potential to dramatically amplify the octopaminergic signal. These OA-dependent peptidergic signaling cascades involve an array of neuropeptides that activate receptors throughout the nervous system and have the potential to both directly and indirectly modulate locomotory decision-making. In this commentary we highlight the use of C. elegans as a model to expand our understanding of noradrenergic signaling in mammals, specifically as it relates to the role of NE in anti-nociception.