Development Of An In-vitro Assay For Neurotrophin-induced Segregation Of Nociceptive And Proprioceptive Sensory Axons

Abstract

Peripheral nerves have the capacity for regeneration and if properly repaired, axon extensions can regenerate even across gaps caused by peripheral nerve loss. Complete functional recovery after gap injury repair remains suboptimal due to the erroneous pathways taken by the regenerating axons leading to aberrant target innervation. A segregation of axonal types can facilitate efficient target direction and innervation leading to improved functional recovery. Novel two-dimensional and three-dimensional Y-shaped assays were developed to test whether the nociceptive and proprioceptive sensory axons from the dorsal root ganglia could be segregated through specific neurotrophin inducement; namely NGF and NT-3 respectively. A large number of the compartmentalized CGRP-positive axons growing toward NGF were long with little to no branches; a characteristic trait prevalent among nociceptive sensory axons. Similarly, the NT-3 attracted CGRP-negative axons that were short and highly arborized are characteristic of proprioceptive neurons. These findings provide evidence of segregation of sensory axonal subtypes using a novel assay and an appropriate delivery system for the release of specific neurotrophins.