Omer Barkai

Abstract Primary nociceptors are essentially characterized as afferent neurons carrying noxious sensory information from the periphery to the CNS. However, the information flow on primary nociceptors is bidirectional. Nociceptor peripheral terminals release a variety of mediators to the target organ in the vicinity of the injured area.

Highlights • Kif2a loss in sensory neurons causes hyperinnervation and hypernociception • Modeling predicts that the aberrant innervation is sufficient to increase the sensitivity • Kif2a deficiency triggers a late homeostatic transcriptional response • This response correlates with the resolution of pain hypersensitivity Summary Nociceptive axons undergo remodeling as they innervate their targets during development and in response to environmental insults and pathological conditions.

Highlights • In corneal nociceptive endings in vivo, Nav-SIZ is located along the terminal fibers • The Nav-SIZ location is dynamic and depends on Nav’s functional availability • Inflammation shifts Nav-SIZ toward the terminal end, rendering it hyperexcitable • This shift of Nav-SIZ may underlie inflammation-induced pain hypersensitivity Summary Nociceptive terminals possess the elements for detecting, transmitting, and modulating noxious signals, thus being pivotal for pain sensation.