Stability and plasticity of primary afferent projections following nerve regeneration and central degeneration

Sensory neurons of the dorsal root ganglia (DRG) regenerate their periphera l axons with relative ease following a nerve lesion. The capacity for centr al regeneration appears more limited. However, after nerve lesion, some DRG neurons gain a regenerative advantage to sprout centrally. We developed a lesion model in the rat to test whether, after prior lesion of their periph eral axons, subsets of cutaneous afferents benefit differently in their abi lity to sprout into adjacent spinal segments denervated by dorsal rhizotomy . We found that under identical circumstances, myelinated sensory neurons, small-diameter peptidergic sensory neurons containing calcitonin gene relat ed peptide (CGRP), and small-diameter nonpeptidergic neurons that bind the lectin from the plant Griffonia simplificolia, isolectin B4 (IB4) differ dr amatically in their ability to regenerate centrally. Myelinated afferent te rminals labelled transganglionically with cholera-toxin beta-subunit gain a small advantage in collaterally sprouting into the adjacent denervated neu ropil in lamina III after prior peripheral nerve lesion. This central regen erative response was not mimicked by experimentally induced inflammation of sensory neuron cell bodies. Intact and unlesioned sensory neurons positive for CGRP sprout vigorously into segments denervated by rhizotomy in a nons omatotopic manner. In contrast, IB4-positive sensory neurons maintain a som atotopic distribution centrally, which is not altered by prior nerve lesion . These data reveal a remarkably heterogeneous response to regeneration-pro moting stimuli amongst three different types of cutaneous sensory neurons. In particular, the divergent responses of peptidergic and nonpeptidergic se nsory neurons suggests profound functional differences between these neuroc hemically distinct neurons.